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At least 685 records · Page 38Linked to original sources
PubMed1999

ACTG 260: a randomized, phase I-II, dose-ranging trial of the anti-human immunodeficiency virus activity of delavirdine monotherapy. The AIDS Clinical Trials Group Protocol 260 Team.

ACTG 260 was an open-label, four-arm trial designed to study the safety and anti-human immunodeficiency virus (anti-HIV) activity of delavirdine monotherapy at three ranges of concentrations in plasma compared to those of control therapy with zidovudine or didanosine. Delavirdine doses were adjusted weekly until subjects were within their target trough concentration range (3 to 10, 11 to 30, or 31 to 50 microM). A total of 113 subjects were analyzed. At week 2, the mean HIV type 1 (HIV-1) RNA level declines among the subjects in the three delavirdine arms were similar (0.87, 1.08, and 1.02 log10 for the low, middle, and high target arms, respectively), but by week 8, the subjects in the pooled delavirdine arms showed only a 0.10 log10 reduction. In the subjects in the nucleoside arm, mean HIV-1 RNA level reductions at weeks 2 and 8 were 0.67 and 0.55 log10, respectively. Because viral suppression by delavirdine was not maintained, the trial was stopped early. Rash, which was usually self-limited, developed in 36% of subjects who received delavirdine. Delavirdine monotherapy has potent anti-HIV activity at 2 weeks, but its activity is time limited due to the rapid emergence of drug resistance.

Acquired Immunodeficiency Syndrome↗
PubMed2004

The HORIZON Recurrent Fracture Trial: design of a clinical trial in the prevention of subsequent fractures after low trauma hip fracture repair.

OBJECTIVE: To present the novel design of a trial testing the safety and efficacy of a yearly bisphosponate, zoledronic acid, in preventing new clinical fractures in patients with recent low trauma hip fracture repair. RESEARCH DESIGN AND METHODS: Randomized, placebo-controlled, triple-blind study. One hundred and fifteen clinical centers worldwide are recruiting approximately 1714 subjects aged 50 years and over (no upper age limit, median age of enrolled subjects to date 79 years) who have undergone surgical repair of a low trauma hip fracture in the preceding 90 days. Patients will be assigned at random to an intervention group (5 mg zoledronic acid intravenously yearly) or a control group (placebo infusion yearly). Both groups receive a loading dose of Vitamin D2 or D3 IM or orally, followed by 800-1200 IU Vitamin D and 1000-1500 mg elemental calcium orally on a daily basis. Concomitant therapy with calcitonin, hormone replacement therapy, selective estrogen receptor modulators, tibolone, and external hip protectors are allowed. MAIN OUTCOME MEASURES: The primary endpoint is subsequent skeletal fractures as adjudicated by a clinical endpoints committee blinded to intervention status. Secondary outcomes include delayed hip fracture healing, changes in bone mineral density, and health resource utilization. Subjects will be recruited over a 3-4 year period and will be followed until 211 primary endpoints are accrued and adjudicated. CONCLUSIONS: This randomized clinical trial is novel among osteoporosis therapies as it (1). targets hip fracture patients, a previously understudied group, and (2). uses only clinically evident fractures as the primary outcome. Ethical and practical considerations in studying this frail population are discussed.

Bone Density↗
PubMed2000

Effect of pregnancy on microvascular complications in the diabetes control and complications trial. The Diabetes Control and Complications Trial Research Group.

OBJECTIVE: To assess the effect of pregnancy on the development and progression of retinopathy and microalbuminuria in type 1 diabetes. RESEARCH DESIGN AND METHODS: We conducted longitudinal analyses of the Diabetes Control and Complications Trial (DCCT), a multicenter controlled clinical trial that compared intensive treatment with conventional diabetes therapy and studied 180 women who had 270 pregnancies and 500 women who did not become pregnant during an average of 6.5 years of follow-up. Women assigned to the conventional treatment group were changed to intensive therapy if they were planning pregnancy or as soon as possible after conception. Fundus photography was performed every 6 months, and the urinary albumin excretion rate (AER) was measured annually. RESULTS: Compared with nonpregnant women, pregnant women had a 1.63-fold greater risk of any worsening of retinopathy from before to during pregnancy (P < 0.05) in the intensive treatment group; the risk was 2.48-fold greater for pregnant vs. not pregnant women in the conventional group (P < 0.001). In the conventional group, the odds of > or =3-step progression from the baseline retinopathy level was >2.9-fold among pregnant vs. not pregnant women (P = 0.003). The odds ratio (OR) peaked during the second trimester (OR = 4.26, P = 0.001) and persisted as long as 12 months postpregnancy (OR = 2.87, P = 0.005). The level of AER during pregnancy in the intensive group, but not in the conventional group, was significantly elevated from the level at baseline, albeit in the normal range. Although individual patients had transient worsening of retinopathy during pregnancy, even to the proliferative level, at the end of the DCCT, mean levels of retinopathy and albuminuria in subjects who had become pregnant were similar to those in subjects who had not become pregnant within each treatment group. CONCLUSIONS: Pregnancy in type 1 diabetes induces a transient increase in the risk of retinopathy; increased ophthalmologic surveillance is needed during pregnancy and the first year postpartum. The long-term risk of progression of early retinopathy and albumin excretion, however, does not appear to be increased by pregnancy.

Adolescent↗
PubMed1997

Phase I/II trial with fozivudine tidoxil (BM 21.1290): a 7 day randomized, placebo-controlled dose-escalating trial.

BACKGROUND AND OBJECTIVES: A Phase I dose-escalating trial with single doses of fozivudine tidoxil (BM21.1290; FZD), in vitro, and experimental in vivo data indicated that further investigations with this compound were warranted. Advantages of fozivudine tidoxil are the direct delivery of zidovudine monophosphate intracellularly and high concentrations in lymphatic tissues. Our objectives were to evaluate safety, tolerability and efficacy of fozivudine tidoxil in human immunodeficiency virus (HIV)-infected patients. PATIENTS AND METHODS: In a Phase I/II dose-escalating trial, three doses of fozivudine tidoxil (400, 800 or 1200 mg/day) were administered for 1 week. The study was randomized and placebo controlled. Inclusion criteria were HIV infection, CD4 count > 100 cells/mm3 and informed consent. The exclusion criteria were active opportunistic infection and prior antiretroviral treatment. RESULTS: The tolerability of fozivudine tidoxil was excellent in all dose groups. No treatment discontinuations were necessary. Steady-state pharmacokinetics did show slightly higher concentrations as compared with levels after the first dose (20%). Viral load reduction was most pronounced in the 1200 mg/day dose group (-0.64 log). No viral load reduction was seen in the placebo group. CONCLUSIONS: The zidovudine conjugate fozivudine tidoxil is safe and well tolerated at the three doses tested. Based on the differences in molecular weights, the 1200 mg dose is roughly equivalent to 400 mg zidovudine.

Adult↗
PubMed1976

[Activity profile of carpipramine. Results of an open trial and a double-blind trial versus doxepin].

During an uncontrolled trial 46 depressed patients (39 endogenous depressions, 5 schizoaffective psychoses and 2 paranoic schizophrenics with depressive syndromes) were treated for 43 days on the average with 3 X 100 mg 1-[3-(10,11-dihydro-5H-dibenz[b,f]-azepin-5-yl)-propyl]-4-piperidino-piperidine-4-carboxamide-dihydrochloride-monohydrate (carpipramine) daily. The clinical impression of the improvement and the results of the Hamilton-Scale for depressions (19 patients, 24 items) showed a clear antidepressive effect of carpipramine. During a double-blind trial 14 patients were treated with carpipramine and 16 with doxepine for 30 days. Most patients suffered from endogenous depressions with paranoic symptoms or from schizophrenia with depressive syndromes. Statistical analysis of the Hamilton-Scale for depressions and the AMP-System showed the antidepressive and antipsychotic effect of carpipramine. Analysis of covariance showed no significant difference between carpipramine and doxepine. Altogether we treated 60 depressive patients with carpipramine. 26 patients improved very well and 11 moderately, that means 37 patients out of 60 reacted positively to therapy with carpipramine. One endogenous depression and a schizoaffective psychosis changed into a manic phase. A provocation of schizophrenic symptoms was not noticed. Carpipramine was very well tolerated and can be classified as a non-sedative antidepressant with an antipsychotic effect.

Anti-Anxiety Agents↗
PubMed1997

MSL-109 adjuvant therapy for cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome: the Monoclonal Antibody Cytomegalovirus Retinitis Trial. The Studies of Ocular Complications of AIDS Research Group. AIDS Clinical Trials Group.

OBJECTIVE: To evaluate the efficacy and safety of an intravenous human monoclonal antibody to cytomegalovirus (CMV), MSL-109, as adjuvant treatment for CMV retinitis. METHODS: Two hundred nine patients with acquired immunodeficiency syndrome and active CMV retinitis were enrolled in a multicenter, phase 2/3, randomized, placebo-controlled clinical trial. Patients received adjuvant treatment with MSL-109, 60 mg intravenously every 2 weeks, or placebo. Randomization was stratified on the basis of whether patients had untreated or relapsed retinitis. Primary drug therapy for CMV retinitis was determined by the treating physician. RESULTS: The rates of retinitis progression, as evaluated in a masked fashion, were 3.04/person-year in the MSL-109-treated group and 3.05/person-year in the placebo-treated group (P=.98; Wald test); the median times to progression were 67 days in the MSL-109-treated group and 65 days in the placebo-treated group. No differences between the 2 groups were noted in the rates of increase in retinal area involved by CMV, visual field loss, or visual acuity outcomes. The mortality rate in the MSL-109-treated group was 0.68/person-year, and in the placebo-treated group, 0.31/person-year (P=.01). The mortality difference was not explained by differences in baseline variables or in concurrent antiretroviral therapy. Among patients with newly diagnosed retinitis, mortality rates were similar (MSL-109, 0.41/person-year; placebo, 0.42/person-year; P=.95), whereas among patients with relapsed retinitis the MSL-109-treated group had a greater mortality rate (MSL-109, 0.83/person-year; placebo, 0.24/person-year; P=.003). However, the mortality rate in the placebo-treated patients with relapsed CMV retinitis was lower than that in the placebo-treated patients with newly diagnosed CMV retinitis and lower than that in other trials of patients with relapsed CMV retinitis. CONCLUSIONS: Intravenous MSL-109, 60 mg every 2 weeks, appeared to be ineffective adjuvant therapy for CMV retinitis. The mortality rate was higher in the MSL-109-treated group, but the reasons for this difference remain uncertain.

AIDS-Related Opportunistic Infections↗
PubMed2000

Nucleoside analogs plus ritonavir in stable antiretroviral therapy-experienced HIV-infected children: a randomized controlled trial. Pediatric AIDS Clinical Trials Group 338 Study Team.

CONTEXT: Although protease inhibitors are used routinely in adults with human immunodeficiency virus (HIV) infection, the role of these drugs in the treatment of clinically stable HIV-infected children is not clear. OBJECTIVE: To evaluate the safety, tolerance, and virologic response produced by a change in antiretroviral therapy in HIV-infected children who were clinically and immunologically stable while receiving previous therapy. DESIGN: The Pediatric AIDS Clinical Trials Group 338, a multicenter, phase 2, randomized, open-label controlled trial conducted from February 6 to April 30, 1997 (patient entry period); patients were followed up for 48 weeks. SETTING: Pediatric HIV research clinics in the United States and Puerto Rico. PATIENTS: Two hundred ninety-seven antiretroviral-experienced, protease inhibitor-naive, clinically stable HIV-infected children aged 2 to 17 years. INTERVENTIONS: Children were randomized to receive zidovudine, 160 mg/m2 3 times per day, plus lamivudine, 4 mg/kg 2 times per day (n = 100); the same regimen plus ritonavir, 350 mg/m2 2 times per day (n = 100); or ritonavir, 350 mg/m2 2 times per day, and stavudine, 4 mg/kg 2 times per day (n = 97). MAIN OUTCOME MEASURE: Plasma HIV-1 RNA levels at study weeks 12 and 48, compared among the 3 treatment groups. RESULTS: At study week 12, 12% of patients in the zidovudine-lamivudine group had undetectable plasma HIV RNA levels (<400 copies/mL) compared with 52% and 54% of patients in the 2- and 3-drug ritonavir-containing groups, respectively (P<.001). Through study week 48, 70% of children continued receiving their ritonavir-containing regimen. At study week 48, 42% of children receiving ritonavir plus 2 nucleosides compared with 27% of those receiving ritonavir and a single nucleoside had undetectable HIV RNA levels (P = .04); however, similar proportions in each group continuing initial therapy had HIV RNA levels of less than 10000 copies/mL (58% vs 48%, respectively; P = .19). CONCLUSIONS: In our study, change in antiretroviral therapy to a ritonavir-containing regimen was associated with superior virologic response at study week 12 compared with change to a dual nucleoside analog regimen. More children receiving ritonavir in combination with 2 compared with 1 nucleoside analog had undetectable HIV RNA levels at study week 48.

Adolescent↗
PubMed2001

Platelet glycoprotein IIb/IIIa integrin blockade with eptifibatide in coronary stent intervention: the ESPRIT trial: a randomized controlled trial.

CONTEXT: The Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy (ESPRIT) trial showed the efficacy of adjunctive, double-bolus eptifibatide therapy in reducing ischemic complications of nonurgent coronary stent implantation at 48 hours and at 30 days. OBJECTIVE: To determine whether the beneficial effects of eptifibatide persist at 6 months after treatment. DESIGN: Follow-up study of a randomized, double-blind, placebo-controlled, crossover-permitted trial conducted from June 1999 through February 2000. SETTING: Ninety-two tertiary care centers in the United States and Canada. PARTICIPANTS: A total of 2064 patients scheduled to undergo nonurgent percutaneous coronary intervention with stent implantation. INTERVENTION: Patients were randomly assigned to receive placebo or eptifibatide (two 180-microg/kg boluses 10 minutes apart and continuous infusion of 2.0 microg/kg per minute), started immediately before stent implantation and continued for 18 to 24 hours. Complete follow-up data were available for 988 (95.0%) of 1040 patients given eptifibatide and 977 (95.4%) of 1024 patients given placebo. MAIN OUTCOME MEASURES: Composite rates of death or myocardial infarction (MI); death, MI, or target vessel revascularization; and their individual components 6 months after enrollment, compared between the 2 groups. RESULTS: By 6 months, the composite end point of death or MI had occurred in 7.5% of eptifibatide-treated patients and in 11.5% of placebo-treated patients (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.47-0.84; P =.002). The composite of death, MI, or target vessel revascularization was 14.2% in eptifibatide-treated patients vs 18.3% in placebo-treated patients (HR, 0.75; 95% CI, 0.60-0.93; P =.008). Most of this benefit accrued early (<48 hours after initiation of therapy) and was maintained through 6 months. Six-month mortality in the eptifibatide group was 0.8% vs 1.4% in the placebo group (HR, 0.56; 95% CI, 0.24-1.34; P =.19) and target vessel revascularization occurred in 8.6% of the eptifibatide group vs 9.4% of the placebo group (HR, 0.91; 95% CI, 0.68-1.22; P =.51). CONCLUSION: Adjunctive eptifibatide therapy during coronary stent implantation provides benefit through 6-month follow-up.

Aged↗
PubMedDate not supplied

Promotion of Breastfeeding Intervention Trial (PROBIT): a randomized trial in the Republic of Belarus.

CONTEXT: Current evidence that breastfeeding is beneficial for infant and child health is based exclusively on observational studies. Potential sources of bias in such studies have led to doubts about the magnitude of these health benefits in industrialized countries. OBJECTIVE: To assess the effects of breastfeeding promotion on breastfeeding duration and exclusivity and gastrointestinal and respiratory infection and atopic eczema among infants. DESIGN: The Promotion of Breastfeeding Intervention Trial (PROBIT), a cluster-randomized trial conducted June 1996-December 1997 with a 1-year follow-up. SETTING: Thirty-one maternity hospitals and polyclinics in the Republic of Belarus. PARTICIPANTS: A total of 17 046 mother-infant pairs consisting of full-term singleton infants weighing at least 2500 g and their healthy mothers who intended to breastfeed, 16491 (96.7%) of which completed the entire 12 months of follow-up. INTERVENTIONS: Sites were randomly assigned to receive an experimental intervention (n = 16) modeled on the Baby-Friendly Hospital Initiative of the World Health Organization and United Nations Children's Fund, which emphasizes health care worker assistance with initiating and maintaining breastfeeding and lactation and postnatal breastfeeding support, or a control intervention (n = 15) of continuing usual infant feeding practices and policies. MAIN OUTCOME MEASURES: Duration of any breastfeeding, prevalence of predominant and exclusive breastfeeding at 3 and 6 months of life and occurrence of 1 or more episodes of gastrointestinal tract infection, 2 or more episodes of respiratory tract infection, and atopic eczema during the first 12 months of life, compared between the intervention and control groups. RESULTS: Infants from the intervention sites were significantly more likely than control infants to be breastfed to any degree at 12 months (19.7% vs 11.4%; adjusted odds ratio [OR], 0.47; 95% confidence interval [CI], 0.32-0.69), were more likely to be exclusively breastfed at 3 months (43.3% vs 6.4%; P<.001) and at 6 months (7.9% vs 0.6%; P =.01), and had a significant reduction in the risk of 1 or more gastrointestinal tract infections (9.1% vs 13.2%; adjusted OR, 0.60; 95% CI, 0.40-0.91) and of atopic eczema (3.3% vs 6.3%; adjusted OR, 0.54; 95% CI, 0.31-0.95), but no significant reduction in respiratory tract infection (intervention group, 39.2%; control group, 39.4%; adjusted OR, 0.87; 95% CI, 0.59-1.28). CONCLUSIONS: Our experimental intervention increased the duration and degree (exclusivity) of breastfeeding and decreased the risk of gastrointestinal tract infection and atopic eczema in the first year of life. These results provide a solid scientific underpinning for future interventions to promote breastfeeding.

Adult↗
PubMed2001

Effects of physical activity counseling in primary care: the Activity Counseling Trial: a randomized controlled trial.

CONTEXT: Physical activity is important for health, yet few studies have examined the effectiveness of physical activity patient counseling in primary care. OBJECTIVE: To compare the effects of 2 physical activity counseling interventions with current recommended care and with each other in a primary care setting. DESIGN: The Activity Counseling Trial, a randomized controlled trial with recruitment in 1995-1997, with 24 months of follow-up. SETTING: Eleven primary care facilities affiliated with 3 US clinical research centers. PARTICIPANTS: Volunteer sample of 395 female and 479 male inactive primary care patients aged 35 to 75 years without clinical cardiovascular disease. INTERVENTIONS: Participants were randomly assigned to 1 of 3 groups: advice (n = 292), which included physician advice and written educational materials (recommended care); assistance (n = 293), which included all the components received by the advice group plus interactive mail and behavioral counseling at physician visits; or counseling (n = 289), which included the assistance and advice group components plus regular telephone counseling and behavioral classes. MAIN OUTCOME MEASURES: Cardiorespiratory fitness, measured by maximal oxygen uptake (VO(2)max), and self-reported total physical activity, measured by a 7-day Physical Activity Recall, compared among the 3 groups and analyzed separately for men and women at 24 months. RESULTS: At 24 months, 91.4% of the sample had completed physical activity and 77.6% had completed cardiorespiratory fitness measurements. For women at 24 months, VO(2)max was significantly higher in the assistance group than in the advice group (mean difference, 80.7 mL/min; 99.2% confidence interval [CI], 8.1-153.2 mL/min) and in the counseling group than in the advice group (mean difference, 73.9 mL/min; 99.2% CI, 0.9-147.0 mL/min), with no difference between the counseling and assistance groups and no significant differences in reported total physical activity. For men, there were no significant between-group differences in cardiorespiratory fitness or total physical activity. CONCLUSIONS: Two patient counseling interventions differing in type and number of contacts were equally effective in women in improving cardiorespiratory fitness over 2 years compared with recommended care. In men, neither of the 2 counseling interventions was more effective than recommended care.

Adult↗
PubMed1990

Adjuvant portal liver infusion in colorectal cancer with 5-fluorouracil/heparin versus urokinase versus control. Results of a prospective randomized clinical trial (colorectal adenocarcinoma trial I).

This prospectively randomized clinical trial was carried out in four Dutch hospitals to reduce the development of metachronous liver metastases and to get a better survival in patients with colorectal malignancies after surgically radical en bloc resection of the primary tumor and the regional lymph nodes. Three hundred seventeen patients were randomized to participate in three trial arms. One group of patients was treated by surgery alone (control group); in the other patients a catheter was placed in the dilated umbilical vein and advanced until the tip was lying in the left branch of the portal vein. Fifty percent of these patients got immediate postoperative portal infusion with 1 g 5-fluorouracil (5-FU) and 5000 U heparin daily for 7 days; the others received portal vein infusion with urokinase 10.000 U/hour for 24 hours only. Three hundred four patients were eligible. Overall hospital mortality was 3.6% (11 patients) and was not influenced by adjuvant treatment. After a median follow-up of 44 months 66 patients have died with relapse and 21 as a result of other causes. The chance of developing liver metastases and other distant metastases after portal infusion with 5-FU/heparin was one third of the chance in the control group (P less than 0.001). Only an insignificant reduction of the average death rate in the 5-FU/heparin group was found. In the urokinase group no significant effect in reducing metastases or in survival was noted. Before recommending cytotoxic portal infusion as an adjuvant treatment in patients with colorectal cancer, detailed analysis of other ongoing portal infusion studies has to be awaited and careful calculations have to be made regarding how many patients really can be saved by this treatment.

Adenocarcinoma↗
PubMed1993

A randomized phase II trial of amonafide or trimetrexate in patients with advanced non-small cell lung cancer. A trial of the North Central Cancer Treatment Group.

BACKGROUND: In an effort to identify new active chemotherapeutic agents against non-small cell lung cancer (NSCLC), the authors conducted a randomized Phase II trial to evaluate the efficacy of amonafide or trimetrexate in patients with Stage IV disease. METHODS: This was a multicenter Cooperative Oncology Group trial. All patients had advanced NSCLC and were previously untreated with chemotherapy. Patients were randomized to treatment after enrollment. Amonafide was administered as a 24-hour continuous infusion (1600 mg/m2) every 21 days. Trimetrexate (150 mg/m2) was administered intravenously over 30 minutes every 2 weeks. The primary endpoints of the study were clinical response and toxic effects. All patients were observed for survival. RESULTS: Thirty-five patients received amonafide and were assessable. There were no complete responses and two partial responses (6%). Thirty-seven patients were treated with trimetrexate. There were no complete responses and five (14%) partial responses. Myelosuppression was the primary toxic effect observed with amonafide treatment. Trimetrexate was associated infrequently with clinically significant side effects. CONCLUSIONS: Amonafide is inactive against NSCLC, and no additional studies with this agent are planned. Trimetrexate has some activity against NSCLC, but its role in the future therapy of this disease is questionable.

Adenine↗
PubMed1979

A clinical trial of endolymphatic therapy in malignant melanoma: interim report of the progress of the Medical Research Council trial.

This report presents the interim results of the MRC trial on the treatment of Stage I melanoma of the lower limb by endolymphatic therapy. Over a 10-year period a group of 146 patients has been entered into the trial. Although total recurrence rates were not significantly affected by endolymphatic therapy, recurrence in the lymph nodes was largely prevented. More patients in the standard treatment group needed the more major procedure of block dissection. The survival rates for the endolymphatic and standard treatment groups did not differ significantly.

Adolescent↗
PubMed1985

Baseline rest electrocardiographic abnormalities, antihypertensive treatment, and mortality in the Multiple Risk Factor Intervention Trial. Multiple Risk Factor Intervention Trial Research Group.

The overall results of the Multiple Risk Factor Intervention Trial (MRFIT) showed a nonsignificant 7% lower coronary artery disease (CAD) mortality rate in the special-intervention (SI) as compared to the usual-care (UC) group. The initial results also suggested that the SI program was more effective than UC in the community in reducing the CAD mortality rate in nonhypertensive persons than in hypertensive persons, and that the SI program used was more effective in reducing CAD deaths among men without than men with electrocardiographic (ECG) abnormalities at rest. Furthermore, an unfavorable mortality trend in hypertensive SI men with ECG abnormalities at rest compared with UC men was noted (adjusted relative risk of 1.67). Further analyses in baseline-defined subgroups indicated that (1) the most common ECG abnormalities at rest were high R waves and ST-T changes, (2) the CAD mortality differential (SI/UC) was similar in the subgroup with these abnormalities and in the subgroup with other abnormalities at rest, (3) the apparent excess CAD mortality among hypertensive SI men with ECG abnormalities at rest was manifested chiefly as sudden death within 1 hour, and (4) the association between ECG abnormalities at rest and the CAD mortality rate among hypertensive men was independent of the baseline level of blood pressure or of the findings on the exercise electrocardiogram. However, CAD mortality in those with abnormalities on the electrocardiogram both at rest and during exercise was lower in the SI than the UC group. A possible explanation for the difference in outcome in the baseline-defined subgroup was an unexpectedly low UC mortality rate. However, within-group analysis revealed an interaction between ECG abnormalities at rest and diuretic treatment in the SI group, with the risk of CAD death for men prescribed diuretic drugs relative to men not prescribed diuretic drugs estimated as 3.34 among men with baseline ECG abnormalities at rest and as 0.95 among men without such abnormalities. No such effect was found in the UC group, in which men generally were prescribed lower doses of hydrochlorothiazide and chlorthalidone than SI men. However, analyses do not suggest an effect of diuretic dose or of hypokalemia on the CAD mortality rate in treated SI participants. Although subgroup analyses must be interpreted with caution, particularly those that go beyond the randomized clinical trial design by the MRFIT, these findings pose hypotheses for investigation by other researchers in systemic hypertension and may have implications for therapy.

Antihypertensive Agents↗
PubMed1985

Exercise electrocardiogram and coronary heart disease mortality in the Multiple Risk Factor Intervention Trial. Multiple Risk Factor Intervention Trial Research Group.

The Multiple Risk Factor Intervention Trial (MRFIT), a coronary heart disease (CAD) primary prevention trial, examined the effect on the CAD mortality rate of a special intervention (SI) program to reduce blood cholesterol level, diastolic blood pressure and cigarette smoking in 35- to 57-year-old men. Half of the 12,866 participants were randomly assigned to usual care (UC) in the community. During 6 to 8 years of follow-up, the CAD mortality rate was 7% lower in the SI than in the UC group, a nonsignificant difference. An a priori subgroup hypothesis proposed that men with a normal electrocardiographic response to a heart-rate-limited exercise test would experience particular benefit from intervention. An abnormal response, defined as an ST-depression integral measured by computer greater than a pre-determined voltage-time cutpoint, was observed in 12.5% of the men at baseline, and was associated with a 3-fold elevation in risk of CAD death within the UC group. In the subgroup with a normal exercise electrocardiographic response, there was no significant SI-UC difference in the CAD mortality rate (16.0 and 13.8 per 1,000, respectively, for SI and UC men). In contrast, there was a 57% lower rate among men in the SI group with an abnormal test result compared with men in the UC group (22.2 vs 51.8 per 1,000). The relative risks (SI/UC) in these 2 strata were significantly different (p = 0.002). These findings suggest that men with elevated risk factors who have an abnormal exercise test response may benefit substantially from risk factor reduction.

Adult↗
PubMed1989

Platelet function during long-term treatment with ketanserin of claudicating patients with peripheral atherosclerosis. A multi-center, double-blind, placebo-controlled trial. The PACK Trial Group.

In a multi-center, double-blind, placebo-controlled trial in claudicating patients with peripheral atherosclerosis, the effects of 1 year of treatment with ketanserin (20 mg t.i.d. for 1 month, 40 mg t.i.d. thereafter; n = 63 patients) or placebo (n = 84 patients) on platelet function (aggregation in P.R.P. by 5-HT 5 x 10(-6) M, ADP 1 to 5 x 10(-6) M, collagen 2 micrograms/ml; platelet 5-HT content; plasma beta TG- and PF4-levels; serum TXB2) were analyzed. Before treatment, claudicating patients (n = 173) displayed an higher reactivity of platelets to 5-HT and signs of platelet activation/release in vivo (higher plasma beta TG-PF4, lower platelet 5-HT content and decreased platelet aggregation by ADP, collagen) in comparison with healthy controls (n = 50). After 1 year of treatment with ketanserin, but not with placebo, platelet aggregation induced by 5-HT (slope -41.1%) and platelet 5-HT content (-23.7%) were significantly reduced. PF4 and beta TG were significantly higher than their pre-medication values in the two trial groups. The other platelet function tests were not significantly modified by the treatment. Only the small subgroup of patients with initially elevated plasma beta TG levels (greater than 20 ng/ml) also scrutinized for hidden NSAID consumption or technical bias (exclusion of data with serum TXB2 less than or equal to 10000 pg/100 microliters and/or plasma PF4 greater than 10 ng/ml) had significantly lower plasma beta TG levels (-22.7%) than the pre-medication values after treatment with ketanserin, but not with placebo. The present study confirms that ketanserin affects some platelet functions, during long-term administration in claudicating patients with atherosclerosis.

Calcium↗
PubMed1996

Design of clinical trials for drug combinations: cytomegalovirus retinitis--foscarnet and ganciclovir. The CMV retinitis retreatment trial.

The Cytomegalovirus Retinitis Retreatment Trial was a multicenter clinical trial designed to evaluate three treatments for the treatment of relapsed CMV retinitis; (1) foscarnet; (2) 'high-dose' ganciclovir, and (3) combination foscarnet and ganciclovir. Two hundred seventy-nine patients were enrolled and randomly assigned to one of these three regimens. Patients were followed monthly for 6 months and every 3 months thereafter. Outcomes of interest included: (1) mortality; (2) retinitis progression; (3) change in retinal area affected by CMV; (4) loss of visual field; (5) loss of visual acuity; (6) quality of life; and (7) treatment side effects.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Lack of blood pressure effect with calcium and magnesium supplementation in adults with high-normal blood pressure. Results from Phase I of the Trials of Hypertension Prevention (TOHP). Trials of Hypertension Prevention (TOHP) Collaborative Research Group.

Phase I of the Trials of Hypertension Prevention (TOHP) was a randomized, multicenter investigation that included double-blind, placebo-controlled testing of calcium and magnesium supplementation among 698 healthy adults (10.5% blacks and 31% women) aged 30 to 54 years with high-normal diastolic blood pressure (DBP) (80 to 89 mm Hg). Very high compliance (94 to 96% by pill counts) with daily doses of 1 g of calcium (carbonate), 360 mg of magnesium (diglycine), or placebos was corroborated for the active supplements by significant net increases in all urine and serum compliance measures in white men and for urine compliance measures in white women. Overall, neither calcium nor magnesium produced significant changes in blood pressure at 3 and 6 months. Analyses stratified by baseline intakes of calcium, magnesium, sodium, or initial blood pressures also showed no effect of supplementation. These analyses suggested that calcium supplementation may have resulted in a DBP decrease in white women and that response modifiers in this subgroup might have included lower initial urinary calcium levels, urinary sodium levels, or lower body mass index. However, overall analyses indicated that calcium and magnesium supplements are unlikely to lower blood pressure in adults with high-normal DBP. The subgroup analyses, useful to formulate hypotheses, raise the possibility of a benefit to white women, which requires testing in future trials.

Administration, Oral↗