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At least 451 records · Page 25Linked to original sources
PubMed1999

Adenosine as an adjunct to thrombolytic therapy for acute myocardial infarction: results of a multicenter, randomized, placebo-controlled trial: the Acute Myocardial Infarction STudy of ADenosine (AMISTAD) trial.

OBJECTIVES: The Acute Myocardial Infarction STudy of ADenosine (AMISTAD) trial was designed to test the hypothesis that adenosine as an adjunct to thrombolysis would reduce myocardial infarct size. BACKGROUND: Reperfusion therapy for acute myocardial infarction (MI) has been shown to reduce mortality, but reperfusion itself also may have deleterious effects. METHODS: The AMISTAD trial was a prospective, open-label trial of thrombolysis with randomization to adenosine or placebo in 236 patients within 6 h of infarction onset. The primary end point was infarct size as determined by Tc-99 m sestamibi single-photon emission computed tomography (SPECT) imaging 6+/-1 days after enrollment based on multivariable regression modeling to adjust for covariates. Secondary end points were myocardial salvage index and a composite of in-hospital clinical outcomes (death, reinfarction, shock, congestive heart failure or stroke). RESULTS: In all, 236 patients were enrolled. Final infarct size was assessed in 197 (83%) patients. There was a 33% relative reduction in infarct size (p = 0.03) with adenosine. There was a 67% relative reduction in infarct size in patients with anterior infarction (15% in the adenosine group vs. 45.5% in the placebo group) but no reduction in patients with infarcts located elsewhere (11.5% for both groups). Patients randomized to adenosine tended to reach the composite clinical end point more often than those assigned to placebo (22% vs. 16%; odds ratio, 1.43; 95% confidence interval, 0.71 to 2.89). CONCLUSIONS: Many agents thought to attenuate reperfusion injury have been unsuccessful in clinical investigation. In this study, adenosine resulted in a significant reduction in infarct size. These data support the need for a large clinical outcome trial.

Adenosine↗
PubMed2026

Urate-lowering effects of losartan: a meta-analysis of randomised controlled trials and target trial emulation.

Common in hypertensive patients, hyperuricaemia is often exacerbated by guideline-recommended antihypertensive therapies such as thiazide diuretics. Losartan is known as an angiotensin II receptor type 1 antagonist with a uricosuric effect, but the magnitude of its efficacy in lowering urate has not been quantified versus a placebo-reference. We sought to quantify the urate-lowering effect of losartan versus placebo using two complementary approaches. We first conducted a meta-analysis of randomised controlled trials (RCTs) to quantify the effect of losartan on serum urate levels versus placebo. We then applied a target trial emulation framework in the UK Biobank as a secondary source of data and a replication experiment. The meta-analysis of six prospective randomised controlled trials (RCTs), including 1119 losartan-treated patients and 1093 controls, demonstrated that losartan reduced serum urate levels by approximately 0.29 mg/dL relative to placebo (95% CI: -0.46 to -0.12, p = 0.0009). In the target trial emulation, 23 losartan-treated individuals showed a reduction in serum urate of approximately 0.35 mg/dL (95% CI: -0.66 to -0.03, p = 0.03) when compared with 92 matched controls, and after accounting for 12 potential confounders including established urate-lowering therapies. Our results provide evidence for a modest yet consistent urate-lowering potential of losartan. This modest biochemical effect (~0.3 mg/dL) may be an attractive option to mitigate the diuretic-induced urate elevation. Thus, losartan can be considered as a favourable antihypertensive choice for patients managed with diuretics or those who are at risk of hyperuricaemia/gout.

Losartan↗
PubMed2002

A randomized placebo-controlled trial of adefovir dipivoxil in advanced HIV infection: the ADHOC trial.

OBJECTIVES: To assess the efficacy and safety of adefovir dipivoxil (ADV) added to stable background antiretroviral therapy (ART) in HIV-infected individuals with advanced HIV disease. METHODS: ADHOC was a randomized, double-blind, placebo-controlled, international multicentre trial. Three hundred and one individuals with CD4 cell counts < 100 cells/microL or < 200 cells/microL with nadir < 50 cells/microL were allocated to receive either 120 mg ADV (subsequently 60 mg) (n = 161) or matching placebo (n = 140) once daily. RESULTS: Over a median follow-up of 76 weeks, 23 (14%) and 18 (13%) participants assigned ADV and placebo, respectively, developed a new AIDS event or died (hazard ratio = 1.23, 95% confidence interval 0.66-2.29, P= 0.51). There was a lower incidence of new or recurrent herpes events in the ADV group (P = 0.009). The mean increase in CD4 cell count from baseline to week 24 was 23.0 and 24.4 cells/ micro L in ADV and placebo groups, respectively (P = 0.89), and the mean decrease in RNA was 0.32 and 0.35 log10 copies/mL at week 24 (P = 0.87) in a subset of participants. There was greater weight loss in the ADV group during the trial (P = 0.007). One hundred and twenty-four participants (41%) had stable background ART in the 8 weeks prior to and the 24 weeks after randomization. There was no significant imbalance in background ART regimens between the two treatment groups. Ninety-seven serious adverse events (SAEs) occurred, 65 and 32 in the ADV and placebo groups, respectively, with significantly shorter time to first SAE in the ADV group (P = 0.002). A total of 33 participants developed proximal renal tubular dysfunction during the trial, all but one in the ADV group. CONCLUSIONS: Due to the early termination of recruitment, ADHOC was unable to assess the original objective of clinical disease progression. Adding ADV to background antiretroviral therapy in advanced HIV disease did not provide immunological or virological improvement compared with placebo. Furthermore, at the doses used in this trial, ADV was associated with a significantly higher incidence of SAEs.

Adenine↗
PubMed2001

Antiepileptogenesis and seizure prevention trials with antiepileptic drugs: meta-analysis of controlled trials.

PURPOSE: To synthesize evidence concerning the effect of antiepileptic drugs (AEDs) for seizure prevention and to contrast their effectiveness for provoked versus unprovoked seizures. METHODS: Medline, Embase, and The Cochrane Clinical Trials Register were the primary sources of trials, but all trials found were included. Minimal requirements: seizure-prevention outcome given as fraction of cases; AED or control assigned by random or quasi-random mechanism. Single abstracter. Aggregate relative risk and heterogeneity evaluated using Mantel-Haenszel analyses; random effects model used if heterogeneity was significant. RESULTS: Forty-seven trials evaluated seven drugs or combinations for preventing seizures associated with fever, alcohol, malaria, perinatal asphyxia, contrast media, tumors, craniotomy, and traumatic brain injury. Effective: Phenobarbital for recurrence of febrile seizures [relative risk (RR), 0.51; 95% confidence interval (CI), 0.32-0.82) and cerebral malaria (RR, 0.36; CI, 0.23-0.56). Diazepam for contrast media-associated seizures (RR, 0.10; CI, 0.01-0.79). Phenytoin for provoked seizures after craniotomy or traumatic brain injury (craniotomy: RR, 0.42; CI, 0.25-0.71; TBI: RR, 0.33; CI, 0.19-0.59). Carbamazepine for provoked seizures after traumatic brain injury (RR, 0.39; CI, 0.17-0.92). Lorazepam for alcohol-related seizures (RR, 0.12; CI, 0.04-0.40). More than 25% reduction ruled out valproate for unprovoked seizures after traumatic brain injury (RR, 1.28; CI, 0.76-2.16), and carbamazepine for unprovoked seizures after craniotomy (RR, 1.30; CI, 0.75-2.25). CONCLUSIONS: Effective or promising results predominate for provoked (acute, symptomatic) seizures. For unprovoked (epileptic) seizures, no drug has been shown to be effective, and some have had a clinically important effect ruled out.

Anticonvulsants↗
PubMed2002

Variation in surgical and anaesthetic technique and associations with operative risk in the European carotid surgery trial: implications for trials of ancillary techniques.

OBJECTIVES: several ancillary surgical techniques, such as shunting and patching, are used in association with carotid endarterectomy. However, the balance of risks and benefits of these techniques is uncertain because of the lack of large randomised controlled trials (RCTs). To assess the potential for further trials, we studied the variation in use of these techniques by surgeon and by country in the European Carotid Surgery Trial (ECST). METHODS: use of each ancillary technique was assessed by surgeon and by country. For each technique, the relationships between the use of the technique and baseline patient characteristics, use of other techniques, and the 30-day operative risk of stroke and death were determined. RESULTS: there was considerable variation between surgeons in the use of ancillary operative techniques both within (p<0.001 for shunting and patching), and between countries (p<0.001 for shunting and patching). Some surgeons used techniques selectively, and so the characteristics of patients differed depending on which techniques were used. Use of each technique was also significantly associated with the use of other techniques. Multiple regression analysis, taking into account all these factors, found no statistically significant associations between operative risk and the use of shunting, patching, intra-operative EEG monitoring, or type of anaesthetic. The only surgical technique significantly associated with an increased operative risk was not using intra-operative anticoagulation (hazard ratio=2.33, 95% CI=1.4-4.2). Other factors associated with an increased risk were an operation time of less than 1 h, or greater than 1.5 h, and the surgeons' subjective assessment that the operation was difficult. CONCLUSIONS: in the ECST, operative risk was more closely related to patient characteristics, length of surgery, and the surgeons' perception of the difficulty of the operation, than to the use of particular ancillary operative techniques. The considerable variation between surgeons, and between countries, in the use of ancillary techniques is in keeping with the lack of convincing data from RCTs, and suggests that there should be sufficient uncertainty to make large pragmatic trials possible.

Aged↗
PubMed1981

Clinical trials for communication aids? A study provoked by the clinical trials of SPLINK.

It is evident that evaluation of communication aids in a functional situation is a necessary part of their development, because of various psychological, social and practical factors related to their acceptability. This is indicated by many unexpected findings in the trial results of one such aid "SPLINK", presented here. This was a multicentre trial with 127 subjects aged between 7 - 82, all of whom had such severe communication problems that spontaneous conversation was limited. The results show that a substantial number of these speech handicapped would benefit from using this aid in various ways and that in some cases it can greatly improve their quality of life. The importance of selection of the aid for the patient and the necessity of expertise on part of the therapist is highlighted by the fact that 80% of users in a previous single centre trial benefitted as compared with 54% in this trial. There are strong indications that attitudes of speech therapists to communication aids range from strongly positive to totally negative; it is vital that they should at least be open-minded as their approach is crucial to outcome.

Adult↗
PubMed2001

Five year follow up of vertically HIV infected children in a randomised double blind controlled trial of immediate versus deferred zidovudine: the PENTA 1 trial.

A total of 195 children were randomised to zidovudine (immediate) or matching placebo (deferred) in a multicentre double blind trial in vertically HIV infected children with early disease (the PENTA 1 trial). Median follow up in the blinded phase was 1.9 years. Thereafter, individual children were unblinded following the results of adult trials showing a benefit of combination antiretroviral therapy (ART) over monotherapy, but follow up continued and is reported here until December 1998 (total follow up 4.6 years). Median time to starting ART in the deferred group was 2.7 years; 19% of deferred children had not started ART by 1999. Throughout follow up, the percentage of time spent on no ART, monotherapy, dual, and triple ART was 21%, 44%, 29%, and 6% respectively for immediate and 62%, 12%, 18%, and 8% for deferred groups. During the blinded phase eight (7.8%) immediate and 12 (13.3%) deferred children developed AIDS or died (log rank p = 0.24); overall 21 immediate and 20 deferred children progressed. In an analysis including all children regardless of original allocation, the risk of progression to AIDS or death, adjusting for age and time since trial entry was significantly lower during 1997-98 (2.4 per 100 child years) than during 1992-96 (6.6 per 100 child years), most likely a result of increased use of combination ART.

Adolescent↗
PubMed2026

Multi-centre randomised controlled feasibility trial with embedded process evaluation of a samba percussion intervention for people living with Parkinson's disease: a protocol for the Sparky Samba trial.

INTRODUCTION: Parkinson's disease (PD) is the second most common neurodegenerative disorder, its principal symptom being deterioration of motor function. Current treatment options are limited to symptom management but there is evidence that physical activity can provide motor benefits. More recently there is evidence to suggest that rhythmic auditory stimulation may improve gait and balance in PD. Sparky Samba is a community initiative in South Wales, UK, founded by a person living with PD. Sessions incorporate the following samba rhythms from a trained facilitator and are held weekly in a community setting. METHODS: The Sparky Samba trial is a multi-site, non-blinded, randomised controlled feasibility trial of Sparky Samba compared with activity as usual. A total of 60 people with PD will be randomised 1:1 to take part in a local Sparky Samba group for 12 weeks or continue their normal activities for the same length of time. The primary outcome is feasibility defined by recruitment, retention, data completeness and intervention adherence. Secondary outcomes relating to motor function, cognition, well-being and self-efficacy will also be assessed at baseline and at 12 weeks. Additionally, we will conduct a process evaluation to understand contextual mechanisms surrounding Sparky Samba. This will be achieved through qualitative interviews and structured participant questionnaires following individual trial completion and through structured questionnaires with intervention delivery staff, supplemented with qualitative interviews. ANALYSIS: Feasibility outcomes will be assessed according to pre-defined criteria. For secondary outcomes, means and standard deviations (or medians and IQRs) will be calculated by arm, alongside 95% CIs for change from baseline to 12-week follow-up. Qualitative data will be subject to thematic analysis using NVivo software. ETHICS AND DISSEMINATION: This study received a favourable ethical opinion from the North of Scotland Research Ethics Committee in April 2025 (REC reference 25/NS/0037). Study results will be disseminated through the peer-review literature, the ISRCTN registry and directly to participants, which will be facilitated by the study's public and patient involvement steering group. TRIAL REGISTRATION NUMBER: ISRCTN11861663.

Humans↗
PubMed2000

Recruitment of patients with lung cancer into a randomised clinical trial: experience at two centres. On behalf of the Big Lung Trial Steering Committee.

BACKGROUND: The entry of patients into randomised clinical trials (RCTs) in lung cancer is low. A study was undertaken to assess the reasons why patients with non-small cell lung cancer did not enter a trial involving randomisation to receive or not receive three courses of cisplatin based chemotherapy in addition to primary treatment by surgery, radiotherapy, or best supportive care. METHODS: The study was carried out in two large London institutions with a special interest in recruiting patients to lung cancer trials. Patients recently diagnosed as having non-small cell lung cancer were prospectively identified and followed to see whether they entered the RCT and, if not, to identify the main reasons why. RESULTS: Six hundred and eighty eight patients newly diagnosed with non-small cell lung cancer were identified between November 1995 and July 1998; 274 (39.8%) were deemed ineligible for the RCT for clinical reasons, most frequently their general condition rendering them unfit for chemotherapy. Another 161 (23.4%) were ineligible for logistical reasons-for example, they were discharged to centres not participating in the RCT or they were not considered for the trial at an appropriate time in their management. Of 253 potentially eligible patients, only 63 (24.9% of those eligible) agreed to enter the RCT and four entered another study. Of those who did not enter, 77 (41.4%) declined without stating a reason, 61 (32.8%) did not want chemotherapy, and only eight (4.3%) expressed a wish to have chemotherapy. CONCLUSIONS: Despite considerable time and effort, the proportion of patients recruited was small (9.2%). Many seen were ineligible but, of 253 potentially eligible patients, 186 (73.5%) refused to enter the RCT.

Adult↗
PubMedDate not supplied

Design of ESPRIT: an international randomized trial for secondary prevention after non-disabling cerebral ischaemia of arterial origin. European/Australian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT) group.

The ESPRIT trial addresses the problem that aspirin, the standard therapy for secondary prevention of vascular complications after a transient ischaemic attack (TIA) or ischaemic stroke of arterial origin, reduces the risk of serious vascular events by only about 13%. Anticoagulants may be an alternative, as these have proved highly efficacious in trials after myocardial infarction and after cerebral ischaemia with atrial fibrillation. After cerebral ischaemia of presumed arterial origin, high-intensity anticoagulation (INR 3.0-4.5) is not safe, but the value of anticoagulation with an INR between 2.0 and 3.0 is still unknown. Secondly, a recent, large trial showed that the combination of aspirin and dipyridamole prevents more major vascular events than aspirin alone, but several earlier trials did not find such an advantage. In ESPRIT, patients with a TIA or minor ischaemic stroke (Rankin grade </=3) will be randomized between oral anticoagulation (INR 2.0-3.0), the combination of dipyridamole (400 mg daily) plus aspirin (in any dose between 30 and 325 mg daily) and aspirin only. Primary outcome is the composite event 'death from all vascular causes, non-fatal stroke, non-fatal myocardial infarction or major bleeding complication', whichever occurs first. Outcome assessment will be blinded. The recruitment of a total of 4,500 patients from more than 10 countries is planned; the mean follow-up will be 3 years.

Anticoagulants↗
PubMed1977

Open trial and double-blind clinical trial of the antidepressant Ro 8-1998 in comparison with imipramine.

Based on the results of an open trial with Ro 8-1998 (chemic name: N,N-dimethyl-3-(1-methyl-5H-dibenzo(a,d)cycloheptene-5-ylidene)-propylamine N-oxide hydrochloride) in 11 endogenous depressed outpatients a double-blind trial with imipramine was proposed. Therapeutic efficacy and side effects of Ro 8-1998 and imipramine were compared in a double-blind trial with 30 patients who were newly hospitalized. Most of them suffered from endogenous depression. On days 0, 5, 10, 15 and 20 the patients were examined and the symptoms were documented with the AMP system, the Hamilton scale for depression, a behaviour rating and the "global depression rating Zurich". Ro 8-1998 caused a decrease of systolic blood pressure, an increase of heart frequency and urea. Twelve out of 15 patients showed a decrease of white blood cells. In four patients the number of white blood cells dropped below 4,000. Statistical analyses proved both substances to be potent antidepressants. The therapeutic efficacy of Ro 8-1998 was at least equal to that of imipramine. Further trials with bigger groups of patients are necessary to show whether the trend towards a better antidepressant efficacy of Ro 8-1998 can be reproduced.

Adult↗
PubMed1997

Generalisability of results from randomised drug trials. A trial on antimanic treatment.

BACKGROUND: Exemplified by a randomised trial on antimanic treatment, this paper addresses the question of whether selection of patients for drug trials may limit the applicability of study results from the randomised patients to a wider population. METHOD: During two-year period, all consecutively admitted patients from a defined catchment area were screened for inclusion criteria concerning age, diagnosis and severity of illness. The subsequently excluded subgroups of patients were compared with the randomised patients by multivariate data analysis. RESULTS: One hundred and sixty-four patients met the inclusion criteria. However, after exclusion for various reasons, only 27 (17%) patients remained for randomisation. The randomised patients and the excluded patients differed substantially. CONCLUSIONS: The generalisability of trial results is limited. Reports of randomised drug trials should carefully describe the screening procedure for inclusion and, when possible, present relevant comparisons-between the randomised patients and the various subgroups of excluded patients.

Adolescent↗
PubMed1999

Phase II trial of N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine.HCl and doxorubicin chemotherapy in metastatic breast cancer: A National Cancer Institute of Canada clinical trials group study.

PURPOSE: This multicenter phase II trial investigated the efficacy and toxicity of a combination of the novel intracellular histamine antagonist, N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine.HCl (DPPE), and doxorubicin in patients with anthracycline-naïve metastatic breast cancer. Preclinical models and early single institutional studies suggested DPPE could potentiate the cytotoxicity of doxorubicin. PATIENTS AND METHODS: Forty-two women, 32 to 77 years old (median, 59 years), with anthracycline-naïve metastatic breast cancer were treated. Patients may have had one previous regimen of nonanthracycline chemotherapy, either in the adjuvant or metastatic disease treatment setting. DPPE (6 mg/kg) was administered as an 80 minute intravenous infusion with doxorubicin (60 mg/m(2)) given intravenously over the last 20 minutes of the DPPE infusion. Patients were premedicated with an antiemetic and sedating regimen. The DPPE/doxorubicin treatment was given every 21 days for a maximum of seven cycles. RESULTS: All 42 patients were assessable. Overall, toxicity was comparable to that expected with doxorubicin alone, with the exception of DPPE-related motion sickness, mild hallucinations, and cerebellar signs at the time of the infusion. These CNS side effects were manageable in an ambulatory care setting, improved with subsequent cycles of treatment, and did not usually require hospitalization. Four patients developed febrile neutropenia. Thirty-five patients received four or more cycles of chemotherapy. The overall response rate was 52.5% (95% confidence interval, 36% to 68%), with 9.5% complete responses (n = 4), 43% partial responses (n = 18), and 38% of patients with stable disease (n = 16). CONCLUSION: The antitumour effects of DPPE/doxorubicin the 52.5% response rate seems encouraging, particularly in consideration of the fact that a recently reported randomized National Cancer Institute of Canada Clinical Trials Group trial using single-agent doxorubicin 60 mg/m(2) in one of the treatment arms achieved a 31% response rate. Thus, a randomized phase III trial of doxorubicin versus doxorubicin plus DPPE is being conducted in this clinical setting.

Adult↗
PubMed2001

Randomized trial of procarbazine, lomustine, and vincristine in the adjuvant treatment of high-grade astrocytoma: a Medical Research Council trial.

PURPOSE: Meta-analyses of the published literature suggest a survival benefit to adjuvant chemotherapy for high-grade astrocytoma, which individual small trials have been unable to demonstrate reliably. The Medical Research Council Brain Tumour Working Party initiated the largest randomized trial of adjuvant chemotherapy for glioma in an attempt to provide a definitive answer. PATIENTS AND METHODS: After surgery, patients aged < or = 70 years, with World Health Organization grade 3 or 4 astrocytoma, were randomized to radiotherapy alone (RT) or RT plus procarbazine, lomustine, and vincristine (PCV) chemotherapy (RT-PCV) given at 6-week intervals to a maximum of 12 courses (procarbazine 100 mg/m2 days 1 to 10, lomustine 100 mg/m2 day 1, and vincristine 1.5 mg/m2 (max 2 mg) day 1). A neuropathology panel independently reviewed all cases. To reliably detect a 10% increase in 2-year survival (from 15% to 25%), 600 patients were required. RESULTS: Between September 1988 and May 1997, 15 United Kingdom centers randomized 674 patients (RT = 339 patients; RT-PCV = 335 patients). With a median follow-up for survivors of 3 years, 617 patients have died, (RT = 310 patients; RT-PCV = 307 patients). Median survival was 9.5 months for RT and 10 months for RT-PCV (hazard ratio = 0.95; 95% confidence interval, 0.81 to 1.11; log-rank P = .50). Tests for interaction revealed no significant differences in treatment effect according to tumor grade, age, performance status, or extent of neurosurgery. CONCLUSION: This trial shows no benefit to PCV chemotherapy, and current data exclude an increase in median survival of more than 10 weeks and in a 1- or 2-year survival rate of more than 7% to 8%. This suggests that no-chemotherapy control arms remain ethical in randomized trials in high-grade astrocytoma.

Adult↗
PubMed2001

Dietary supplement use in the Prostate Cancer Prevention Trial: implications for prevention trials.

Nutrients included in commonly used dietary supplements, such as vitamins C and E, may affect cancer risk. To better understand how supplement use may affect the interpretation of cancer prevention trials, we examined dietary supplement use among participants in the Prostate Cancer Prevention Trial, a double-blind, placebo-controlled trial of the drug finasteride (Proscar) for the primary prevention of prostate cancer. Of 15,387 men who completed food frequency questionnaires and dietary supplement questionnaires, 44.3% used a multivitamin, 35% used single supplements of vitamin C or E, and 10-15% used antioxidant mixtures or single supplements of vitamins A and D, zinc, or beta-carotene at least three times per week. The strongest correlates of supplement use were higher education and lower body mass index (p < 0.001), and whites and Asians were more likely to use multivitamins and single supplements of vitamins C and E than were blacks and Hispanics. Supplement users obtained 87% of their total daily vitamin E intake, 61-64% of vitamins A, C, and D, and about half of beta-carotene, folate, and zinc from supplements. Because supplements, especially antioxidants, may confer independent cancer-preventive effects, analytic models of study findings should include exposure measurement of dietary supplements with appropriate tests for interaction. Our results can be generalized to similar chemoprevention trials.

Aged↗
PubMed1994

The Hypertension in the Very Elderly Trial (HYVET). Rationale, methodology and comparison with previous trials.

The Hypertension in the Very Elderly Trial (HYVET) is a multicentre, open, randomised, controlled trial. The aim of this trial is to investigate the effect of active treatment on stroke incidence in hypertensive patients over the age of 80 years. Secondary end-points include total cardiovascular mortality and morbidity. Entry criteria include a sustained sitting systolic blood pressure of 160 to 219mm Hg plus a sustained sitting diastolic pressure of 95 to 109mm Hg. Also required is a standing systolic blood pressure of at least 140mm Hg. Patients must give their informed consent, and be free of congestive heart failure requiring treatment, gout, renal failure or a recent cerebral haemorrhage. Patients are to be randomised to 3 groups-(i) no treatment; (ii) treatment with a diuretic [bendroflumethiazide (bendrofluazide)]; or (iii) treatment with an angiotensin converting enzyme (ACE) inhibitor (lisinopril). Starting dosage for bendroflumethiazide and lisinopril is 2.5 mg/day. In order to achieve goal sitting systolic and diastolic blood pressures (< 150/80 mm Hg), a doubling of the dosage is allowed. Furthermore, slow release diltiazem (120 mg/day increasing to 240 mg/day if required) may be added to the medication of the actively treated groups. These drugs have been chosen as inexpensive and appropriate representatives of their therapeutic classes. 700 patients in each group (a total of 2100) will be sufficient to detect a 40% difference in cerebrovascular events between no treatment and active treatment (alpha = 0.01, 1-beta = 0.90). These numbers will also detect a difference in total mortality of 25% and in cardiovascular mortality of 35%. The pilot phase of the trial has been started with support from the British Heart Foundation. Centres which are interested in taking part should contact C.J. Bulpitt or any of the other authors.

Aged↗
PubMed1992

Results of the Cancer Research Campaign Adjuvant Trial for Perioperative Cyclophosphamide and Long-Term Tamoxifen in Early Breast Cancer reported at the tenth year of follow-up. Cancer Research Campaign Breast Cancer Trials Group.

Over 2,000 patients with early breast cancer were recruited into a trial between 1980 and 1985. This trial was of a factorial 2 x 2 design to investigate the benefits of a short course of perioperative cyclophosphamide or tamoxifen 20 mg daily for 2 years. At the tenth year of follow-up no significant benefit is noted for perioperative cyclophosphamide, however the main effect analysis for adjuvant tamoxifen demonstrates a significant improvement in disease-free survival which increases with time during the follow-up period. These results are in keeping with the World Overview of Trials of Adjuvant Tamoxifen. However, this study is unique, having a large number of node negative patients and over 500 premenopausal women in a comparison of tamoxifen and control. The relative risk reductions for the node negative patients for disease-free survival are greater than for the node positive patients. This might suggest that the absolute benefit for adjuvant tamoxifen is similar in both groups of patients, bearing in mind the increased risk of relapse with the node positive patients. No trend for interaction emerges according to age or menopausal status suggesting an identical benefit for premenopausal women. Of particular interest is the development of contralateral breast cancer. The initial overall effect which emerged at the third year of follow-up ceases to be apparent. However, subgroup analysis according to menopausal status suggests a trend for interaction with a reduction in the risk of contralateral breast cancer in the postmenopausal women and an increase in the risk of contralateral breast cancer in premenopausal women. Plausible mechanisms exist to explain this difference in outcome and these data need to be checked against other large trials of adjuvant tamoxifen at a time when we are considering the chemoprophylaxis of breast cancer in high risk premenopausal women.

Breast Neoplasms↗
PubMed2000

Acute thromboscintigraphy with (99m)Tc-apcitide: results of the phase 3 multicenter clinical trial comparing 99mTc-apcitide scintigraphy with contrast venography for imaging acute DVT. Multicenter Trial Investigators.

UNLABELLED: (99m)Tc-apcitide (formerly known as (99m)Tc-P280) is a radiolabeled peptide that binds with high affinity and specificity to the glycoprotein IIb/IIIa receptors expressed on the activated platelets that are involved in acute thrombosis. The purpose of the phase 3 multicenter clinical trials was to compare (99m)Tc-apcitide scintigraphy with contrast venography for imaging acute deep venous thrombosis (DVT). METHODS: A total of 280 patients were enrolled in 2 clinical trials conducted in North America and Europe. Patients were to be within 10 d of onset of signs and symptoms of acute DVT or within 10 d of surgery associated with a high risk of DVT. (99m)Tc-apcitide scintigraphy and contrast venography were to be performed within 36 h. Planar scintigraphic images were obtained at 10, 60, and 120-180 min after injection. (99m)Tc-apcitide scintigrams and contrast venograms were read with masking and also by the institutional investigators. RESULTS: Of a total of 243 patients who were evaluable, 61.7% were receiving heparin at the time of imaging. Masked reading of (99m)Tc-apcitide scintigraphy, compared with masked reading of contrast venography, had a sensitivity, specificity, and agreement of 73.4%, 67.5%, and 69.1%, respectively, which met the prospectively defined target efficacy endpoint in both trials. Institutional reading of (99m)Tc-apcitide scintigraphy, compared with institutional reading of contrast venography, had a sensitivity, specificity, and agreement of 75.5%, 72.8%, and 74.0%, respectively. However, the entire trial population included patients with a history of DVT who may have had old, nonacute venous thrombi that could confound the venography results. Therefore, data from patients having no history of DVT or pulmonary embolism and who presented within 3 d of onset of signs and symptoms (n = 63), i.e., patients for whom a venogram would be expected to be positive only if acute DVT were present, also were analyzed as a subset. In these patients, institutional reading of (99m)Tc-apcitide scintigraphy, compared with institutional reading of contrast venography, had a sensitivity, specificity, and agreement of 90.6%, 83.9%, and 87.3%, respectively. CONCLUSION: (99m)Tc-apcitide scintigraphy is a new diagnostic modality that is highly sensitive for imaging acute DVT.

Acute Disease↗