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At least 721 records · Page 40Linked to original sources
PubMed1982

Controlled trial of slow-release aminophylline in childhood asthma: are short-term trials valid?

Slow-release aminophylline, although widely used for the prophylaxis of childhood asthma, has had only limited formal assessment. A four-month double-blind cross-over trial of slow-release aminophylline (14 mg/kg twice daily) was carried out in 24 children with perennial asthma. Satisfactory serum theophylline concentrations were obtained in 17 children, with few side effects. There was a significant improvement in mild daytime and night-time symptoms. The incidence of more severe symptoms was unaffected. Treatment did not improve the mean peak expiratory flow or reduce the incidence of use of bronchodilators. It is concluded that slow-release aminophylline has a place in the prophylaxis of perennial childhood asthma but is unsuitable for children who suffer from severe attacks. The cross-over trial design has severe limitations.

Adolescent↗
PubMed1989

Verapamil versus hydrochlorothiazide in the treatment of hypertension: results of long term double blind comparative trial. Verapamil versus Diuretic (VERDI) Trial Research Group.

OBJECTIVE: To compare the efficacy and tolerability of hydrochlorothiazide, sustained release verapamil, and their combination in patients with mild to moderate hypertension. DESIGN: Randomised multicentre trial of 48 weeks' duration with a double blind comparison of hydrochlorothiazide and verapamil followed by an open trial of combined treatment for patients not achieving the target diastolic blood pressure (less than 90 mm Hg) during treatment with a single drug. SETTING: Outpatient departments in 10 clinics and 10 private practices of general practitioners or internists. PATIENTS: 369 Hypertensive patients with a diastolic blood pressure of 95-120 mm Hg during a placebo run in period of two weeks. INTERVENTIONS: Initial treatment consisted of 12.5 mg hydrochlorothiazide (n = 187) or 120 mg sustained release verapamil (n = 182) once daily (regimen I). If the target diastolic blood pressure of less than 90 mm Hg was not achieved within four weeks doses were increased to 25 mg hydrochlorothiazide or 240 mg verapamil once (regimen II) and twice daily (regimen III). Patients not achieving target blood pressure were given the combination of hydrochlorothiazide and verapamil--that is, 25 and 240 mg once (regimen IV) and twice daily (regimen V). MAIN OUTCOME MEASURE: Blood pressure determined with a device permitting automatic repeated measurements with printouts. RESULTS: After eight weeks of treatment with a single drug 76 out of 178 (43%) and 101 out of 175 (58%) patients achieved the target blood pressure with hydrochlorothiazide and verapamil, respectively. During follow up until 48 weeks patients treated with verapamil reached the target blood pressure more often and at lower doses and were less likely to switch to combination treatment than patients randomised to hydrochlorothiazide treatment. Adding verapamil to hydrochlorothiazide was more effective than the addition of hydrochlorothiazide to verapamil. At the end of the study 42 out of 169 (25%) and 73 out of 163 (45%) patients initially randomised to hydrochlorothiazide and verapamil, respectively, were at target blood pressure without combination treatment. After adding verapamil to hydrochlorothiazide or hydrochlorothiazide to verapamil an additional 58 (34%) and 29 (18%) patients reached the target blood pressure, respectively. Altogether 92 out of 332 (28%) patients failed to achieve target blood pressure with regimen V. There were four, 10, seven, and seven withdrawals due to possible adverse effects to treatment with hydrochlorothiazide, verapamil, combining verapamil with hydrochlorothiazide, and combining hydrochlorothiazide with verapamil, respectively. CONCLUSIONS: In doses currently used in antihypertensive treatment verapamil was more effective than hydrochlorothiazide as a single agent and in combination in mild to moderate hypertension, whereas withdrawal rates caused by side effects possibly related to treatment were similar.

Adult↗
PubMed1998

Randomized trial of an oral platelet glycoprotein IIb/IIIa antagonist, sibrafiban, in patients after an acute coronary syndrome: results of the TIMI 12 trial. Thrombolysis in Myocardial Infarction.

BACKGROUND: Inhibitors of the platelet glycoprotein IIb/IIIa receptor given intravenously have been shown to be effective in reducing ischemic complications after coronary angioplasty and in unstable angina, making this a promising new class of agents for the treatment and prevention of ischemic events in patients with acute coronary syndromes. Sibrafiban (Ro 48-3657) is an oral, peptidomimetic, selective antagonist of the glycoprotein IIb/IIIa receptor. METHODS AND RESULTS: The Thrombolysis in Myocardial Infarction (TIMI) 12 trial was a phase II, double-blind, dose-ranging trial designed to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of sibrafiban in 329 patients after acute coronary syndromes. In the PK/PD cohort of TIMI 12, 106 patients were randomized to receive one of seven dosing regimens of sibrafiban, ranging from 5 mg daily to 10 mg twice daily for 28 days. In the safety cohort, 223 patients were randomized to one of four dose regimens of sibrafiban (ranging from 5 mg twice daily to 15 mg once daily) or aspirin for 28 days. High levels of platelet inhibition were achieved: mean peak values ranged from 47% to 97% inhibition of 20 micromol/L ADP-induced platelet aggregation on day 28 across the seven doses. Twice-daily dosing provided more sustained platelet inhibition (mean inhibition, 36% to 86% on day 28), whereas platelet inhibition returned to baseline levels by 24 hours with once-daily dosing. Major hemorrhage occurred in 1.5% of patients treated with sibrafiban and in 1.9% of patients treated with aspirin. Protocol-defined "minor" bleeding, usually mucocutaneous, occurred in 0% to 32% of patients in the various sibrafiban groups and in none of the patients treated with aspirin. Minor bleeding was related to total daily dose (P=.002), once- versus twice-daily dosing (P<.0001), renal function (P<.0001), and presentation with unstable angina (P<.01). CONCLUSIONS: The oral glycoprotein IIb/IIIa antagonist sibrafiban achieved effective, long-term platelet inhibition with a clear dose-response but at the expense of a relatively high incidence of minor bleeding. Oral IIb/IIIa inhibition deserves further study as a new treatment strategy in patients after acute coronary syndromes.

Acute Disease↗
PubMed1993

Feasibility and efficacy of sodium reduction in the Trials of Hypertension Prevention, phase I. Trials of Hypertension Prevention Collaborative Research Group.

Phase I of the Trials of Hypertension Prevention was a multicenter, randomized trial of the feasibility and efficacy of seven nonpharmacologic interventions, including sodium reduction, in lowering blood pressure in 30- to 54-year-old individuals with a diastolic blood pressure of 80 to 89 mm Hg. Six centers tested an intervention designed to reduce dietary sodium to 80 mmol (1800 mg)/24 h with a total of 327 active intervention and 417 control subjects. The intervention consisted of eight group and two one-to-one meetings during the first 3 months, followed by less-intensive counseling and support for the duration of the study. The mean net decrease in sodium excretion was 43.9 mmol/24 h at 18 months. Women had lower sodium intake at baseline and were therefore more likely to decrease to less than 80 mmol/24 h. Black subjects were less likely to decrease to less than 80 mmol/d, independent of sex or baseline sodium excretion. The mean (95% confidence interval) net decrease associated with treatment was -2.1 (-3.3, -0.8) mm Hg for systolic blood pressure and -1.2 (-2.0, -0.3) mm Hg for diastolic blood pressure at 18 months (both P < .01). Multivariate analyses indicated a larger systolic blood pressure effect in women (-4.44 versus -1.23 mm Hg in men), adjusted for age, race, baseline blood pressure, and baseline 24-hour urinary sodium excretion (P = .02). Dose-response analyses indicated an adjusted decrease of -1.4 mm Hg for systolic blood pressure and -0.9 mm Hg for diastolic blood pressure for a decrease of 100 mmol/24 h in 18-month sodium excretion. These results support the utility of sodium reduction as a population strategy for hypertension prevention and raise questions about possible differences in dose response associated with gender and initial level of sodium intake.

Adult↗
PubMed2002

Randomized adjuvant trial of tamoxifen and goserelin versus cyclophosphamide, methotrexate, and fluorouracil: evidence for the superiority of treatment with endocrine blockade in premenopausal patients with hormone-responsive breast cancer--Austrian Breast and Colorectal Cancer Study Group Trial 5.

PURPOSE: Effective adjuvant treatment modalities in premenopausal breast cancer patients today include chemotherapy, ovariectomy, and tamoxifen administration. The purpose of Austrian Breast and Colorectal Cancer Study Group Trial 5 was to compare the efficacy of a combination endocrine treatment with standard chemotherapy. PATIENTS AND METHODS: Assessable trial subjects (N = 1,034) presenting with hormone-responsive disease were randomized to receive either 3 years of goserelin plus 5 years of tamoxifen or six cycles of cyclophosphamide, methotrexate, and fluorouracil (CMF). Stratification criteria included tumor stage and grade, number of involved nodes, type of surgery, and steroid hormone receptor content. Relapse-free survival (RFS) was defined as time from randomization to first relapse, local recurrence, or contralateral incidence, and overall survival (OS) as time to date of death. RESULTS: With a 60-month median follow-up, 17.2% of patients in the endocrine group and 20.8% undergoing chemotherapy developed relapses. Local recurrences emerged in 4.7% and 8.0%, respectively. RFS and local recurrence-free survival differed significantly in favor of endocrine therapy (P =.037 and P =.015), with a similar trend observed in OS (P =.195). CONCLUSION: Overall, our data suggest that the goserelin-tamoxifen combination is significantly more effective than CMF in the adjuvant treatment of premenopausal patients with stage I and II breast cancer.

Antineoplastic Agents, Hormonal↗
PubMed2003

Phase III randomized trial of 12 versus 3 months of maintenance paclitaxel in patients with advanced ovarian cancer after complete response to platinum and paclitaxel-based chemotherapy: a Southwest Oncology Group and Gynecologic Oncology Group trial.

PURPOSE: To determine whether continuing paclitaxel for an extended time period in women with advanced ovarian cancer who had achieved a clinically defined complete response to a platinum/paclitaxel-based chemotherapy could prolong subsequent progression-free survival (PFS) and affect ultimate survival. PATIENTS AND METHODS: Patients were randomly assigned to either three or 12 cycles of single-agent paclitaxel administered every 28 days and were then followed up for progression-free and overall survival. RESULTS: As of September 6, 2001, 277 patients (262 assessable) had entered the trial, with a total of 54 PFS events having developed among 222 patients with follow-up data. With the exception of peripheral neuropathy, there were no major differences in toxicity between the regimens. The median PFS was 21 and 28 months in the three-cycle and 12-cycle paclitaxel arms, respectively. One-sided P values from an unadjusted log-rank test and an adjusted Cox model analysis (for stratification factors) were.0035 and.0023, respectively, both in favor of the 12-cycle arm. The Cox model-adjusted three-cycle versus the 12-cycle progression hazard ratio was estimated to be 2.31 (99% confidence interval, 1.08 to 4.94). With a protocol-specified early termination boundary of P =.005, these findings led the Southwest Oncology Group Data Safety Monitoring Committee to discontinue the trial. As of the date of study closure, there was no difference in overall survival between the treatment arms. CONCLUSION: Twelve cycles of single-agent paclitaxel administered to women with advanced ovarian cancer who attain a clinically defined complete response to initial platinum/paclitaxel-based chemotherapy significantly prolongs the duration of PFS.

Aged↗
PubMed2005

Phase III trial of paclitaxel plus carboplatin with or without tirapazamine in advanced non-small-cell lung cancer: Southwest Oncology Group Trial S0003.

PURPOSE: Tumor hypoxia confers chemotherapy resistance. Tirapazamine is a cytotoxin that selectively targets hypoxic cells. We conducted a phase III clinical trial to determine whether the addition of tirapazamine to paclitaxel and carboplatin offered a survival advantage when used in the treatment of patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Of 396 patients registered, 367 eligible patients were randomly assigned to either arm 1 (n = 181), which consisted of treatment every 21 days with paclitaxel 225 mg/m2/3 h, carboplatin (area under the curve = 6), and tirapazamine 260 mg/m2 in cycle 1 (which was escalated, if tolerable, to 330 mg/m(2) in cycle 2), or arm 2 (n = 186), which consisted of paclitaxel and carboplatin as in arm 1 with no tirapazamine. RESULTS: Patient characteristics were similar between the two arms. There were no statistically significant differences in response rates, progression-free survival, or overall survival. Patients on arm 1 had significantly (P < .05) more abdominal cramps, fatigue, transient hearing loss, febrile neutropenia, hypotension, myalgias, and skin rash and were removed from treatment more often as a result of toxicity than patients in arm 2 (26% v 13%, respectively; P = .003). More than 40% of patients did not have the tirapazamine dose escalated, primarily because of toxicity. The trial was closed early after an interim analysis demonstrated that the projected 37.5% improvement in survival (8 v 11 months median survival) in arm 1 was unachievable (P = .003). CONCLUSION: The addition of tirapazamine to paclitaxel and carboplatin does not result in improved survival in advanced NSCLC compared with paclitaxel and carboplatin alone but substantially increases toxicity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Sapporo Fitness Club Trial (SFCT)--design, recruitment and implementation of a randomized controlled trial to test the efficacy of exercise at a fitness club for the reduction of cardiovascular risk factor--.

BACKGROUND: The annual health check followed by lifestyle recommendations has long been the standard national strategy to improve cardiovascular disease (CVD) risk factors in Japan. Exercise at fitness clubs, now widely accessible in major cities, has a novel appeal as a strategy with the additive effect of CVD risk reduction. The Sapporo Fitness Club Trial (SFCT) is a randomized controlled trial to compare the efficacy of the national standard alone (control) with the standard plus exercise at a fitness club (intervention) for the reduction of CVD risk factors. METHODS: The SFCT has recruited and randomized 561 relatively inactive overweight men and women, aged 40-85 years, with elevated levels of 2 or more of the following: systolic blood pressure, fasting blood glucose, and low-density lipoprotein cholesterol. The intervention group was required to exercise at a fitness club 2-4 times per week. At the end of 6 months, risk factors, aerobic capacity, health-related quality of life measures, and adverse effects are to be compared. CONCLUSION: The SFCT is expected to have a major impact in Japan on public health recommendations on exercise for the reduction of lifestyle-related disease.

Adult↗
PubMed1996

Nevirapine, zidovudine, and didanosine compared with zidovudine and didanosine in patients with HIV-1 infection. A randomized, double-blind, placebo-controlled trial. National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group Protocol 241 Investigators.

OBJECTIVE: To study the addition of a third human immunodeficiency virus type 1 (HIV-1) reverse transcriptase inhibitor, nevirapine, to the combination of zidovudine and didanosine. DESIGN: A 48-week, randomized, double-blind, placebo-controlled trial at 16 AIDS (acquired immunodeficiency syndrome) Clinical Trials Units. PATIENTS: 398 adults who had HIV-1 infection, had 350 or fewer CD4+ T lymphocytes/mm3, and had had more than 6 months of previous nucleoside therapy. INTERVENTION: 1) Either nevirapine or placebo (200 mg/d for 2 weeks, then 400 mg/d thereafter) and 2) open-label zidovudine (600 mg/d) and didanosine (400 mg/d for patients weighing > or = 60 kg). MEASUREMENTS: CD4+ T lymphocyte counts, time to first HIV-1 disease progression event or death, adverse events, and nevirapine levels in plasma samples taken at random were measured in all patients. Plasma levels of HIV-1 RNA HIV-1 infectivity titer in peripheral blood mononuclear cells; serum p24 antigen levels; and plasma levels of zidovudine and didanosine were measured in patients enrolled at half the study sites. RESULTS: After 48 weeks of study treatment the patients assigned to the triple-combination regimen (nevirapine, zidovudine, and didanosine) had an 18% higher mean absolute CD4 cell count (95% Cl, 7% to 29%; P = 0.001), a 0.32 log10 lower mean infectious HIV-1 titer in peripheral blood mononuclear cells (Cl, 0.05 to 0.59 log10 infectious units per million cells; P = 0.023), and a 0.25 log10 lower mean plasma HIV-1 RNA level (Cl, 0.03 to 0.48 log10 RNA copies/mL; P = 0.028) than did patients assigned to the double-combination regimen (zidovudine and didanosine). Severe rashes were more common among patients assigned to receive the triple combination (9% compared with 2%; P = 0.002). Risk for disease progression did not differ between the two groups (relative hazard of the triple-combination group, 1.24 [Cl, 0.75 to 2.06]; P > 0.2), although the study had only moderate power to detect a major difference. CONCLUSIONS: Adding nevirapine to zidovudine and didanosine improved the long-term immunologic and virologic effects of therapy and was associated with severe rash among the patients studied, who had had extensive previous therapy. These results support 1) the continuing development of combinations of more than two antiretroviral drugs to increase and prolong HIV-1 suppression and 2) the potential utility of nevirapine in combination regimens.

Adult↗
PubMed1999

Artificial Valve Endocarditis Reduction Trial (AVERT): protocol of a multicenter randomized trial.

BACKGROUND AND AIM OF THE STUDY: This article presents the protocol of the Artificial Valve Endocarditis Reduction Trial (AVERT), a multicenter, international randomized trial to assess the efficacy of the SilzoneTM coating of St. Jude Medical Masters Series mechanical heart valves in the prevention of prosthetic heart valve endocarditis (PVE). A total of 4,400 eligible patients will be randomized within three years of study commencement at 17 participating clinical centers in North America and Europe, with study completion within four years. ELIGIBILITY CRITERIA: Eligible patients are candidates for St. Jude mechanical valves with either the Silzone or conventional cuff, in the mitral and/or aortic position, who give informed written consent to participate. Major exclusion criteria are the presence of prosthetic valves that do not require replacement, and the need for tricuspid valve replacement. Bypass surgery and valve repair are allowed during the implant operation. Patients will be randomized using an envelope-based intraoperative randomization scheme, stratified by clinical center and by the presence of endocarditis at the time of surgery. FOLLOW UP: Patients will be contacted at discharge, three months, and each anniversary of the implant procedure. A brief follow up survey, administered via clinic interview, telephone or mail, will elicit events associated with possible endocarditis (unexplained fever, worsening angina, hospitalization) that will initiate contact with the patient's following physician. OUTCOME ANALYSIS: The primary PVE endpoint will be based upon a published algorithm, with two infectious disease specialists making the final determination of cases classified as possible endocarditis. Study data will be periodically reviewed by a Data Safety Monitoring Board. The primary analysis will be an intention-to-treat comparison of freedom from PVE curves between the Silzone and conventional cuff treatment groups. CONCLUSIONS: AVERT will provide much-needed information on the effectiveness of Silzone in preventing PVE, as well as practice patterns and outcomes of valve replacement.

Clinical Protocols↗
PubMed2000

Results of the low-dose (20 mg) pravastatin GISSI Prevenzione trial in 4271 patients with recent myocardial infarction: do stopped trials contribute to overall knowledge? GISSI Prevenzione Investigators (Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico).

BACKGROUND: The aim of this study was to test the efficacy of a low-dose pravastatin regimen (20 mg daily) in patients with myocardial infarction. METHODS: GISSI Prevenzione (GISSI-P) is an open trial on secondary coronary heart disease prevention: 4271 recent acute myocardial infarction patients (< or = 6 months) with total blood cholesterol > or = 200 mg/dl were randomized to low-dose cholesterol-lowering treatment (pravastatin 20 mg daily) or no treatment. GISSI-P was started in 1993 and its story was crossed by the publication of the results of similarly designed clinical trials. The publication of 4S results in 1994 prompted the Data Safety and Monitoring Board (DSMB) and the Steering Committee (SC) to change the protocol so that only patients whose total blood cholesterol was < 250 mg/dl could be randomized whilst patients with total blood cholesterol > 250 mg/dl who had already been enrolled in the study had to be re-evaluated and, if appropriate, pharmacologically treated. The DSMB and the SC agreed to stop randomization prematurely in late 1996 after the publication of CARE results. RESULTS: Mean follow-up time was 23.0 +/- 6.7 months (median 24.3 months). The two treatment groups were well matched at baseline. Pharmacological interventions recommended by the protocol were widely prescribed (antiplatelet agents > 90%, beta-blockers 42.7%, and ACE-inhibitors 40.2%). Mainly because of the on-course modification of the study protocol, 402/2133 (18.8%) patients in the control group started a cholesterol-lowering treatment during follow-up. Conversely, 296/2138 (13.8%) patients permanently stopped taking their tablets. Side effects, however, were the reason for discontinuing therapy in 57 (2.7%) patients in the pravastatin group, and patient reluctance to continue accounted for most of the remainder. After excluding control patients who had started a cholesterol-lowering treatment during follow-up, the following changes of median lipid concentrations in the control group over the whole course were observed: total cholesterol -1.9%; LDL cholesterol -2.9%; triglycerides -2.0%; HDL cholesterol +1.4%. The analysis carried out excluding patients randomized to pravastatin treatment and actually not assuming the drug clearly indicated the cholesterol-lowering efficacy of low-dose pravastatin (total cholesterol -12.5%; LDL cholesterol -18.8%; triglycerides -7.9%; HDL cholesterol +3.4%). During the study 256 (6.0%) patients either died or had a non-fatal stroke or a myocardial infarction, 136 (6.4%) in the control group and 120 (5.6%) in the pravastatin group (relative risk 0.90, 95% confidence interval 0.71-1.15, p = 0.41); 160 patients died, 88 (4.1%) in the control group and 72 (3.4%) in the pravastatin group (relative risk 0.84, 94% confidence interval 0.61-1.14, p = 0.26). The few (n = 28) non-cardiovascular deaths were balanced: 16 (0.8%) in the control group and 15 (0.6%) in the pravastatin group. The reduction of cardiovascular events was more evident in the by-treatment analysis, with coronary heart disease deaths being significantly decreased (relative risk 0.60, 95% confidence interval 0.38-0.96, p = 0.04). The overall frequency of adverse events was similar in the two groups. No significant difference between treatment groups was found for total cases of cancer or at any particular site. CONCLUSIONS: Despite the decreased statistical power due to its premature stopping, the results of the GISSI-P suggest that a low-dose treatment with pravastatin (20 mg daily) is effective in reducing blood lipids, and underline the importance of long-term compliance with treatments in the search for a maximal effective dosage. Furthermore, the effects of a statin on total and coronary mortality quantified for the first time in a population exposed to Mediterranean dietary and lifestyle habits are markedly consistent with those obtained in different settings.

Aged↗
PubMed1990

Hypertension Prevention Trial (HPT): food pattern changes resulting from intervention on sodium, potassium, and energy intake. Hypertension Prevention Trial Research Group.

The Hypertension Prevention Trial (HPT) was a multicenter randomized trial designed to assess the effects of long-term dietary changes on blood pressure in a normotensive population (diastolic blood pressure greater than or equal to 78 but less than 90 mm Hg) for a period of 3 years. The dietary treatments were reduction of sodium intake, increase of potassium intake, and decrease of energy intake. Estimates of changes in food intake were made by comparing 24-hour food records of the treatment and control participants. The participants in the treatment groups reported sodium intakes that were 30% to 40% lower than those of the controls. The restriction was achieved mainly by reducing intake of salt, meats, and grain products. Meats and grain products were still a major source of total sodium intake after treatment (41% to 47%), perhaps because of continued use of processed foods. Potassium intake was reported to be 16% to 25% higher in the treatment groups than in the controls, the increase achieved largely through increased consumption of fruits, with a lesser contribution from vegetables. Participants with higher initial body weights reported smaller increases in fruit and vegetable consumption than participants of normal weight, perhaps because of concerns about weight gain. Energy intake in the weight loss groups was 8% to 11% less than that of the controls. Men reported success in restricting calories from meats, dairy products, fats, beverages, and sugars. Women were less successful in restricting calories from most food groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1990

An assessment of diltiazem and hydrochlorothiazide in hypertension. Application of factorial trial design to a multicenter clinical trial of combination therapy.

This multicenter, factorial-design trial assessed the safety and additive antihypertensive efficacy of a slow-release (SR) formulation of diltiazem hydrochloride given alone or in combination with hydrochlorothiazide for treatment of mild to moderate hypertension. After a 4- to 6-week placebo run-in period, 297 qualifying patients were randomized to receive placebo, 1 of 4 doses of diltiazem SR monotherapy, 1 of 3 doses of hydrochlorothiazide monotherapy, or 1 of 12 possible combinations of diltiazem SR and hydrochlorothiazide for 6 weeks. A dose-related reduction in blood pressure was demonstrated for each drug as monotherapy and for the two drugs in combination. Absolute blood pressures of patients who received combination therapy were lower by an overall mean of 3.0 mm Hg diastolic and 8.0 mm Hg systolic vs diltiazem SR used alone and 3.5 mm Hg diastolic and 4.0 mm Hg systolic vs hydrochlorothiazide used alone. At the largest doses used, 50% of patients achieved goal blood pressure while taking hydrochlorothiazide, 57% while taking diltiazem SR, and 75% while taking combination therapy. Combination therapy was well tolerated. This trial clearly demonstrates that diltiazem SR and hydrochlorothiazide have additive antihypertensive effects.

Adult↗
PubMed1985

Metoprolol in acute myocardial infarction (MIAMI). A randomised placebo-controlled international trial. The MIAMI Trial Research Group.

The effect of metoprolol on mortality and morbidity after 15 days, was compared with that of placebo in a double-blind randomised international trial (the MIAMI trial) in patients with definite or suspected acute myocardial infarction (AMI). Treatment with intravenous metoprolol (15 mg) or placebo was started shortly after the patient's arrival in hospital within 24 h of the onset of symptoms, and then oral treatment (200 mg daily) was continued for the study period (15 days). Of the 5778 patients included, 2901 were allocated to placebo and 2877 to metoprolol. Definite AMI was confirmed in 4127 patients. There were 142 deaths in the placebo group (4.9%) and 123 deaths in the metoprolol group (4.3%), a difference of 13 per cent with 95 per cent confidence limits of -8 to +33 per cent, not statistically significant (P = 0.29). Previously recorded risk indicators of mortality were analysed in retrospect. These indicated that there was a category which showed higher risk which contained approximately 30% of all randomized patients. In these, the mortality rate in the metoprolol treated group was 29% less than in the placebo group. In the remaining lower risk categories there was no difference between the treatment groups. This subset analysis must be interpreted with caution in view of the findings from other similar studies. Positive effects were observed on the incidence of definite AMI and on serum enzyme activity in patients treated early (less than 7 h). There was no significant effect on ventricular fibrillation but the number of episodes tended to be lower in the metoprolol treated patients during the later phase (6-15 days; 24 vs 54 episodes). The incidence of supraventricular tachyarrhythmias, the use of cardiac glycosides and other antiarrhythmics, and the need for pain-relieving treatment were significantly diminished by metoprolol amongst all randomised patients. Adverse events associated with metoprolol were infrequent, expected, and relatively mild.

Aged↗
PubMed1987

The Lopressor Intervention Trial: multicentre study of metoprolol in survivors of acute myocardial infarction. Lopressor Intervention Trial Research Group.

The Lopressor Intervention Trial (LIT) was a double-blind, randomized, placebo-controlled, multicentre study designed to evaluate the effect of oral metoprolol on overall mortality in patients surviving a recent acute myocardial infarction. Patient enrollment began in August 1979 and ended on 15 April 1982, with 2395 patients (1200 on placebo and 1195 on metoprolol). Hospitalized patients, 45 to 74 years of age, began therapy from 6 to 16 days after their myocardial infarction. Following a short titration period, maintenance therapy with metoprolol 100 mg b.i.d. or placebo was continued for up to 1 year. Enrollment was prematurely terminated because of a progressive and marked decline in patient accession; it was not feasible to reach the original goal of 3200 patients in a practical period of time. This target sample size was based on an anticipated 1 year placebo mortality rate of 10%, a 50% reduction in total mortality with metoprolol and premature discontinuation of study medication in no more than 15% of patients in the metoprolol group. Two primary analyses were planned: total mortality among all randomized patients at 7 and at 12 months of trial entry. After 7 months of treatment there were 54 deaths in the placebo group and 42 deaths in the metoprolol group. After 1 year there were 62 deaths in the placebo group and 65 in the metoprolol group. Thus, the 1 year placebo mortality rate of 5.2% was half that predicted at the outset. In addition, study medication was prematurely discontinued in over 30% of patients in the metoprolol group.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1988

Effect of intravenous APSAC on mortality after acute myocardial infarction: preliminary report of a placebo-controlled clinical trial. AIMS Trial Study Group.

A randomised double-blind placebo-controlled clinical trial was undertaken to assess survival after a single 30 unit intravenous dose of anisoylated plasminogen streptokinase activator complex (APSAC) within 6 h of onset of acute myocardial infarction. A planned interim analysis of mortality data was undertaken after 1004 patients had been followed for at least 30 days after randomisation. 61 (12.2%) of 502 patients on placebo died within 30 days compared with 32 (6.4%) of 502 patients on APSAC (p = 0.0016). Because of this 47% reduction in 30-day mortality (95% confidence interval 21-65%) patient entry to the trial was terminated. Preliminary 1 year mortality data show a similar trend. Percentage mortality reduction with APSAC was similar whether time since onset of symptoms was 0-4 h (660 patients) or 4-6 h (344 patients). Adverse events were few. These findings add to evidence that intravenous thrombolytic therapy after myocardial infarction offers a substantial reduction in mortality.

Adult↗
PubMed1988

First results on mortality reduction in the UK Trial of Early Detection of Breast Cancer. UK Trial of Early Detection of Breast Cancer Group.

Between 1979 and 1981 the UK Trial of Early Detection of Breast Cancer enrolled women aged 45-64 living in eight locations in the United Kingdom. Annual screening by clinical examination of the breast, with mammography in alternate years, was provided over 7 years for 45,841 women; 63,636 were offered teaching in breast self-examination and were provided with a self-referral clinic; and 127,117, for whom no extra services were provided, form a comparison population. Over the 7 years from the start of the trial a reduction in the risk of dying from breast cancer in women offered screening relative to that in the comparison population was observed. The reduction was 14% (RR 0.86, 95% CI 0.69-1.08) when no allowance was made for underlying differences in breast cancer mortality between the populations, but rose to 20% (RR 0.80, 95% CI 0.64-1.01) when adjusted for differences in pretrial mortality rates. These differences fall short of statistical significance. No reduction in mortality was observed during the first 5 years but thereafter the gap widens. These results, though in themselves inconclusive, are consistent with the hypothesis that screening can achieve a worthwhile mortality reduction. No difference in mortality has so far been observed between women offered teaching in breast self-examination and the comparison population.

Breast Neoplasms↗
PubMed1988

Surfactant replacement therapy at birth: final analysis of a clinical trial and comparisons with similar trials.

A randomized trial of surfactant replacement therapy at birth was conducted at the University of Rochester between June 1983 and November 1985. Thirty-four premature infants, 25 to 29 weeks' gestational age, received a preventilatory dose of a calf lung surfactant extract in saline prepared at the University of Rochester. A control group of 31 infants received a preventilatory dose of saline alone. The major finding of this trial is that a single preventilatory dose of calf lung surfactant extract reduces the severity of the respiratory distress syndrome during the first 24 hours of life. The beneficial effects, however, are not sustained in many infants and diminish after 24 hours of life. The survival rate was 71% in both the control and surfactant-treated groups. There was a lower incidence of pneumothorax in the surfactant-treated group. There were no differences in the incidence of bronchopulmonary dysplasia, patent ductus arteriosus, and intraventricular hemorrhage. No adverse effects of surfactant replacement therapy were identified. Results of this study suggest that multiple postventilatory doses of surfactant will be required for optimal therapy.

Clinical Trials as Topic↗