The FEVER (Felodipine EVEnt Reduction) trial; a randomised, double-blind, placebo-controlled trial in Chinese hypertensive patients

The FEVER trial observed the difference between intense and less intense treatment of hypertension by comparing combination therapy consisting of a low diuretic dose (12.5 mg of hydrochlorothiazide) and a low calcium antagonist dose (5 mg of felodipine) with monotherapy based on a low diuretic dose (12.5 mg of hydrochlorothiazide) in Chinese hypertensive patients. The trial enrolled 9711 hypertonics (of which 4841 on hydrochlorothiazide + felodipine combination and 4870 on hydrochlorothiazide + placebo combination). Blood pressure decreased from 158.7/92.4 to 138.1/82.3 mmHg and from 158.0/92.7 to 141.6/83.9 mmHg in the combination therapy group and monotherapy group, respectively. The average difference throughout the trial was 4.2/2.1 mmHg. The primary endpoint--fatal and non-fatal stroke (CVA)--was reduced by 27% in the combination therapy group. Among secondary endpoints, the success ratio of combination therapy was expressed by 27% reduction of all cardiovascular events, 35% reduction of all cardiac events, 32% reduction of coronary events and 31% reduction of deaths. The minor difference between systolic and diastolic blood pressure of approximately 4/2 mmHg was related to a decrease in the incidence of CVA and cardiovascular events in Chinese hypertonics.     

The beta-agonist lung injury trial (BALTI): a randomized placebo-controlled clinical trial

RATIONALE: Experimental data suggest that manipulation of alveolar fluid clearance with beta-agonists can accelerate the resolution of alveolar edema and improve survival. OBJECTIVE: To determine if a sustained infusion of intravenous salbutamol (albuterol) would accelerate the resolution of alveolar edema in adult patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). METHODS: This was a single-center, double-blind, randomized controlled trial. Patients with ALI/ARDS were randomized to treatment with intravenous salbutamol (15 microg kg(-1) h(-1)) or placebo for 7 d. The primary endpoint was extravascular lung water measured by thermodilution (PiCCO) at Day 7. MEASUREMENTS AND MAIN RESULTS: Sixty-six patients were screened; of these, 40 met the inclusion criteria and were enrolled during 2001-2003. Patients in the salbutamol group had significantly lower lung water at Day 7 than the placebo group (9.2 +/- 6 vs. 13.2 +/- 3 ml kg(-1); 95% confidence interval difference, 0.2-8.3 ml kg(-1); p = 0.038). Plateau airway pressure was lower at Day 7 in the salbutamol group (23.9 +/- 3.8 cm H2O) versus placebo (29.5 +/- 7.2 cm H2O; p = 0.049). There was a trend toward lower Murray lung injury score at Day 7 in the salbutamol group (1.7 +/- 0.9) versus placebo (2.0 +/- 0.6; p = 0.2). Patients in the salbutamol group had a higher incidence of supraventricular arrhythmias (26 vs. 10%; p = 0.2). CONCLUSION: Although further research is required to confirm the efficacy and safety of intravenous salbutamol in ALI/ARDS, this trial provides the first proof of principle that, in humans with ALI/ARDS, sustained treatment with intravenous beta-agonists reduces extravascular lung water.     

The long-term effects of non-steroidal anti-inflammatory drugs in osteoarthritis of the knee: a randomized placebo-controlled trial

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat osteoarthritis (OA), though their long-term efficacy is uncertain. We report a comparison of the symptomatic responses to therapy with tiaprofenic acid, indomethacin and placebo over 5 yr. METHODS: A parallel-group, randomized, single-blind trial of patients with knee OA recruited 812 patients from 20 centres; 307 patients received tiaprofenic acid (300 mg b.d.), 202 indomethacin (25 mg t.d.s.) and 303 matching placebo for up to 5 yr. At the end of the parallel-group study, patients receiving tiaprofenic acid or placebo entered a 4-week blinded cross-over study of tiaprofenic acid or placebo, both given for 2 weeks. Assessments were at baseline, 4 weeks, then at 6-month intervals for up to 5 yr in the parallel group study and at 2-week intervals in the cross-over study. They comprised pain scores, duration of morning stiffness, patients' global assessments, paracetamol consumption, adverse reactions, withdrawals and functional outcomes. RESULTS: There were significant falls in overall pain scores in patients receiving NSAIDs compared with placebo at 4 weeks in the parallel-group phase. Thereafter there were no advantages favouring active therapy. In the cross-over phase, pain scores were significantly lower in patients receiving tiaprofenic acid than placebo. Patients who had been receiving long-term tiaprofenic acid showed significant rises in their pain scores when receiving placebo therapy and vice versa. Adverse events were reported by 61% of patients receiving tiaprofenic acid, 63% on indomethacin and 51% on placebo. Potentially severe side-effects were rare; for example, there were only three cases of gastrointestinal bleeding on NSAIDs. The pattern of withdrawal was similar in patients taking NSAIDs and placebo in the parallel-group study; at 48 weeks 53% of the patients remained on tiaprofenic acid, 50% on indomethacin and 54% on placebo. CONCLUSIONS: NSAIDs significantly reduce overall pain over 4 weeks. This short-term responsiveness is retained, and even after several years of therapy with tiaprofenic acid pain scores increased over 2 weeks when it was changed to placebo. Our results do not show long-term benefits from the use of NSAIDs in OA and the majority of patients had persisting pain and disability despite therapy.     

Felodipine in chronic stable angina: a randomized, double-blind, placebo-controlled, crossover study

To investigate the antianginal efficacy and tolerability of felodipine, a new dihydropyridine calcium antagonist, 20 patients with stable exertional angina, not completely controlled by beta-blocker monotherapy, entered a randomized, double-blind, placebo-controlled, crossover study. Patients on standard beta-blocker therapy, who had at least 3 weekly anginal episodes and a reproducible exercise test (stopped for angina and ECG signs of ischaemia) at the end of 2 weeks placebo treatment, were eligible for the study. They were randomized to one sequence of treatment: felodipine 5 mg twice daily for 2 weeks followed by placebo for a further 2 weeks, or vice versa. Beta-blocker treatment was unchanged throughout the study. A treadmill test was carried out at the end of each crossover period, 2-4 h after drug administration. The number of anginal attacks and nitroglycerin consumption was recorded on a diary card. At rest, felodipine significantly (P less than 0.05) reduced standing systolic but not diastolic blood pressure. Heart rate was not modified by the active treatment. At ischaemic threshold and at peak exercise, heart rate, systolic blood pressure and rate-pressure product remained unchanged. Exercise duration was increased by felodipine (P less than 0.01) and maximal ST change was reduced (P less than 0.01). Time to 1 mm ST depression was prolonged non-significantly by felodipine (basal 5.7 +/- 1.5, felodipine 7.4 +/- 2.0, placebo 6.6 +/- 1.5 min). The number of patients who stopped exercise due to angina and ST change was 20/20 at baseline, 16/20 with placebo and 10/20 with felodipine. Felodipine significantly reduced weekly anginal episodes (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Roflumilast in Asian patients with COPD: A randomized placebo-controlled trial

Background and objective: Roflumilast, an oral, selective phosphodiesterase 4 inhibitor, has been shown to reduce exacerbations and improve pulmonary function in patients with COPD. This study examined the efficacy, safety and tolerability of roflumilast in Asian patients with COPD. Methods: Patients with COPD were randomized 1:1 to enter a 12‐week treatment period and receive either oral roflumilast, 500 µg once daily, or placebo, following a single‐blind, 4‐week baseline period in which all patients received placebo. The primary end point was mean change in FEV₁ from baseline to each postrandomization visit during the treatment period. Other spirometric lung function measurements were evaluated as secondary end points. COPD exacerbations were monitored. Safety was assessed from clinical laboratory tests, vital signs, physical examination (including electrocardiogram) and monitoring of adverse events (AEs). Results: Of 551 patients recruited, 410 were randomized and received at least one dose of study medication (roflumilast, n = 203; placebo, n = 207). Superiority of roflumilast over placebo was demonstrated by a statistically significant difference in postbronchodilator FEV₁ (79 mL, P < 0.0001). Other spirometry end points, including prebronchodilator FEV₁, pre‐and postbronchodilator FEV₆, forced vital capacity and peak expiratory flow significantly favoured roflumilast over placebo. AEs were more common with roflumilast than with placebo, but were comparable with those reported in previous studies. Conclusions: Roflumilast, 500 µg once daily, improves pulmonary function in Asian patients with COPD. The safety and tolerability of roflumilast in this population was similar to that in a Caucasian population.     

Felodipine in addition to beta-adrenergic blockade for angina pectoris.A multicentre, randomized, placebo-controlled trial

The additional efficacy, duration of action and tolerabilityof felodipine were evaluated in patients with stable anginapectoris and a positive stress test who were already receivingtherapy with a beta-adrenergic blocker. One hundred and twenty-eightpatients were randomized to double-blind treatment with 5–10mg felodipine once daily or matching placebo, and were evaluatedby serial exercise testing during 12 weeks of treatment. Felodipine at 4 h significantly increased exercise durationassessed after 4 weeks of treatment (increase 34 ±65s vs 18±71 s in placebo-treated patients; 95% confidenceinterval 1.01–1.11; P=0.01), and after 12 weeks of treatment(increase 39 ± 103 s vs 3 ± 72 s; 95% confidenceinterval 1.01–1.16; P=0.02). The time until onset of exercise-inducedanginal pain and time until 1 mm ST depression assessed after4 weeks of treatment also increased significantly with felodipinecompared to placebo. No statistically significant changes inexercise test parameters evaluated 24 h after medication wereobserved. The addition of felodipine once daily demonstrated a sustainedimprovement in exercise duration in patients symptomatic despitetreatment with a beta-blocker evaluated 4 h after drug intake.At 24 h post dose, no statistically significant effect was observed.Felodipine is well tolerated with a low incidence of side-effectsand no adverse effect on quality of life.     

Addition of spironolactone in patients with resistant arterial hypertension (ASPIRANT): a randomized, double-blind, placebo-controlled trial

There is currently limited data on which drug should be used to improve blood pressure (BP) control in patients with resistant hypertension. This study was designed to assess the effect of the addition of 25 mg of spironolactone on BP in patients with resistant arterial hypertension. Patients with office systolic BP >140 mm Hg or diastolic BP >90 mm Hg despite treatment with at least 3 antihypertensive drugs, including a diuretic, were enrolled in this double-blind, placebo-controlled, multicenter trial. One hundred seventeen patients were randomly assigned to receive spironolactone (n=59) or a placebo (n=58) as an add-on to their antihypertensive medication, by the method of simple randomization. Analyses were done with 111 patients (55 in the spironolactone and 56 in the placebo groups). At 8 weeks, the primary end points, a difference in mean fall of BP on daytime ambulatory BP monitoring (ABPM), between the groups was -5.4 mm Hg (95%CI -10.0; -0.8) for systolic BP (P=0.024) and -1.0 mm Hg (95% CI -4.0; 2.0) for diastolic BP (P=0.358). The APBM nighttime systolic, 24-hour ABPM systolic, and office systolic BP values were significantly decreased by spironolactone (difference of -8.6, -9.8, and -6.5 mm Hg; P=0.011, 0.004, and 0.011), whereas the fall of the respective diastolic BP values was not significant (-3.0, -1.0, and -2.5 mm Hg; P=0.079, 0.405, and 0.079). The adverse events in both groups were comparable. In conclusion, spironolactone is an effective drug for lowering systolic BP in patients with resistant arterial hypertension.     

Pentoxifylline improves nonalcoholic steatohepatitis: a randomized placebo-controlled trial

The primary aim of this study was to compare the effects of pentoxifylline (PTX) versus placebo on the histological features of nonalcoholic steatohepatitis (NASH). In all, 55 adults with biopsy-confirmed NASH were randomized to receive PTX at a dose of 400 mg three times a day (n = 26) or placebo (n = 29) over 1 year. The primary efficacy endpoint was defined as improvement in histological features of NASH through reduction in steatosis, lobular inflammation, and/or hepatocellular ballooning as reflected by a decrease of ≥ 2 points in the nonalcoholic fatty liver disease (NAFLD) activity score (NAS). After 1 year, intention-to-treat analysis showed a decrease of ≥ 2 points in the NAS in 38.5% of patients on PTX versus 13.8% of those on placebo (P = 0.036). Per protocol analysis, a decrease of ≥ 2 points in the NAS from baseline was observed in 50% of the patients on PTX versus 15.4% of those on placebo (P = 0.01). The mean change in NAS score from baseline was -1.6 in the PTX group, versus -0.1 in the placebo group (P < 0.001). PTX significantly improved steatosis (mean change in score -0.9 versus -0.04 with placebo, P < 0.001) and lobular inflammation (median change -1 versus 0 with placebo, P = 0.02). No significant effects in hepatocellular ballooning were observed. PTX also improved liver fibrosis (mean change in fibrosis score was -0.2 among those on PTX versus +0.4 among those on placebo, P = 0.038). Although not statistically significant (P = 0.17), improvement in fibrosis was observed in a greater proportion (35%) of patients in the PTX group compared to placebo (15%). Adverse effects were similar in both groups. CONCLUSION: PTX improved histological features of NASH compared to placebo. PTX was well tolerated in patients with NASH.     

Infliximab plus azathioprine for steroid-dependent Crohn's disease patients: a randomized placebo-controlled trial

BACKGROUND & AIMS: The aim of this study was to evaluate the usefulness of short-term infliximab combined with azathioprine (AZA) or 6-mercaptopurine (6-MP) in steroid-dependent Crohn's disease patients. METHODS: Patients with active disease despite prednisone given for more than 6 months were eligible and were stratified as follows: the failure stratum consisted of patients receiving AZA/6-MP at a stable dose for more than 6 months, and the naive stratum consisted of patients not treated previously with AZA/6-MP. Patients were randomized to infliximab 5 mg/kg or placebo at weeks 0, 2, and 6. All patients were treated with AZA/6-MP maintained at a stable dose throughout the 52 weeks of the study. The primary end point was remission off steroids at week 24. RESULTS: Among the 113 enrolled patients (55 in the failure stratum), 57 were assigned to infliximab. At week 24, the success rate (intent-to-treat analysis) was higher in the infliximab group than in the placebo group (57% vs 29%; P = .003); at weeks 12 and 52, the corresponding rates were 75% vs 38% (P < .001) and 40% vs 22% (P = .04), respectively. In each stratum, the success rate was significantly higher in the infliximab group at weeks 12 and 24, and a trend was found at week 52. In the failure stratum, only 27% of the patients in the infliximab group were still in remission off steroids, compared with 52% in the naive stratum. Steroid resistance was less common and the cumulative dose of prednisone was lower in the infliximab group. CONCLUSIONS: Infliximab plus AZA/6-MP is more effective than AZA/6-MP alone in steroid-dependent Crohn's disease patients.     

Efficacy and safety of infliximab in patients with ankylosing spondylitis: results of a randomized, placebo-controlled trial (ASSERT)

OBJECTIVE: The signs and symptoms of ankylosing spondylitis (AS) respond inadequately to nonsteroidal antiinflammatory drugs, corticosteroids, and disease-modifying antirheumatic drugs in quite a number of patients. Tumor necrosis factor inhibitors have demonstrated success in reducing AS disease activity in a limited number of clinical trials. The objective of this multicenter, randomized, placebo-controlled study was to evaluate the efficacy and safety of infliximab in patients with AS. METHODS: Patients were randomly assigned to receive infusions of placebo or 5 mg/kg infliximab at weeks 0, 2, 6, 12, and 18. Efficacy was assessed using the ASsessment in Ankylosing Spondylitis (ASAS) International Working Group criteria, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), night pain, patient's global assessment, the Bath Ankylosing Spondylitis Functional Index (BASFI), the Bath Ankylosing Spondylitis Metrology Index (BASMI), chest expansion, the Mander enthesis index, the total swollen joint index, the C-reactive protein level, and the Short Form 36 (SF-36) health survey questionnaire. The primary end point in this study was the proportion of patients with a 20% improvement response according to the ASAS International Working Group criteria (ASAS20 responders) at week 24. RESULTS: Of the 357 patients screened, 201 were assigned to receive 5 mg/kg infliximab and 78 were assigned to receive placebo. After 24 weeks, 61.2% of patients in the infliximab group were ASAS20 responders compared with 19.2% of patients in the placebo group (P < 0.001). Clinical benefit was observed in patients receiving infliximab as early as week 2 and was maintained over the 24-week study period. Patients receiving infliximab also showed significant improvements in the BASDAI, BASFI, BASMI, chest expansion, and physical component summary score of the SF-36. Adverse events were reported by 82.2% of patients receiving infliximab and by 72.0% of patients receiving placebo; however, most adverse events in both treatment groups were mild or moderate in severity. CONCLUSION: Infliximab was well tolerated and effective in a large cohort of patients with AS during a 24-week study period.     

Orlistat in hypertensive overweight/obese patients: results of a randomized clinical trial

OBJECTIVE: To assess the effect of orlistat plus diet compared with diet alone in promoting weight loss and blood pressure reduction in hypertensive, overweight/obese patients. DESIGN: A pragmatic randomized, controlled trial. SETTING: Hypertension clinic of a university hospital. PATIENTS: Hypertensive patients aged 18-75 years with a body mass index greater than 25 kg/m(2). INTERVENTIONS: Orlistat 360 mg/day combined with a hypocaloric diet (treatment group), or a calorie-restricted diet alone (control group). MAIN OUTCOME MEASURES: Primary outcomes were reductions in weight and blood pressure. Secondary outcomes were decreases in lipid and glucose concentrations. A subgroup analysis of the main outcomes among diabetic and non-diabetic patients was also performed. RESULTS: A total of 204 patients were included in the intention-to-treat analysis. After 12 weeks the orlistat group lost, on average, 3.7 kg and the control group lost 2.0 kg in weight (P < 0.001). Systolic (SBP) and diastolic (DBP) blood pressures decreased by 15.3 and 11.4 mmHg, respectively, in the group given orlistat plus a hypocaloric diet and by 11.6 and 5.2 mmHg, respectively, in the control group given the calorie-restricted diet alone (P = 0.25 and P = 0.0004, respectively). Fasting glucose (0.82 and 0.17 mmol/l, P = 0.01) and total cholesterol (0.85 and 0.56 mmol/l, P = 0.05) were reduced to a greater extent with orlistat than with diet alone. The mean reduction in triglycerides with orlistat plus the hypocaloric diet was 0.75 mmol/l and that in the control group was 0.30 mmol/l (P = 0.28); the increases in high-density lipoprotein cholesterol were 0.05 and 0.00 mmol/l, respectively, in the two groups (P = 0.17). Treatment improved blood pressure and glucose control in the individuals with diabetes, but not in those without diabetes. CONCLUSION: In both groups there was a reduction in weight, blood pressure and metabolic parameters. The orlistat group performed better in reducing weight, DBP, glucose and cholesterol. Results show that even a small reduction in weight helps to control blood pressure and glucose. The cost-benefit of the use of orlistat should be evaluated for hypertensive obese patients.     

Effect of a long-term oral l-arginine supplementation on glucose metabolism: a randomized, double-blind, placebo-controlled trial

Aim: This study assessed the efficacy of long-term l-arginine (l-arg) therapy in preventing or delaying type 2 diabetes mellitus. Methods: A mono-centre, randomized, double-blind, parallel-group, placebo-controlled, phase III trial (l-arg trial) was conducted on 144 individuals affected by impaired glucose tolerance (IGT) and metabolic syndrome (MS). l-Arg/placebo was administered (6.4 g/day) on a background structured lifestyle intervention for 18 months plus a 12-month extended follow-up period after study drug termination. Fasting glucose levels and glucose tolerance after oral glucose tolerance test were evaluated throughout the study. Results: After 18 months, l-arg as compared with placebo did not reduce the cumulative incidence of diabetes [21.4 and 20.8%, respectively, hazard ratio (HR), 1.04; 95% confidence interval (CI), 0.58-1.86] while the cumulative probability to become normal glucose tolerant (NGT) increased (42.4 and 22.1%, respectively, HR, 2.60; 95% CI, 1.51-4.46, p < 0.001). The higher cumulative probability to become of NGT was maintained during the extended period in subjects previously treated with l-arg (HR, 3.21; 95% CI, 1.87-5.51; p < 0.001). At the end of the extended period, the cumulative incidence of diabetes in subjects previously treated with l-arg was reduced as compared with placebo (27.2 and 47.1%, respectively, HR, 0.42; 95% CI, 0.24-0.75, p < 0.05). During both periods, l-arg significantly improved insulin sensitivity and β-cell function. Conclusion: Among persons with IGT and MS, the supplementation of l-arg for 18 months does not significantly reduce the incidence of diabetes but does significantly increase regression to NGT.     

Effect of potassium supplementation on blood pressure in Chinese: a randomized, placebo-controlled trial.

OBJECTIVE: To examine the effect of potassium supplementation on blood pressure (BP) in a Chinese population who consume a habitual high sodium and low potassium diet. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Community sample from Beijing, China. PARTICIPANTS: A total of 150 men and women aged 35-64 years with an initial systolic BP 130-159 mmHg and/or diastolic BP 80-94 mmHg. INTERVENTIONS: Participants were randomly assigned to take 60 mmol potassium chloride supplement or placebo for 12 weeks. MAIN OUTCOME MEASURE(S): BP measurements were obtained at baseline, and at 6 weeks and 12 weeks during the trial, using random-zero sphygmomanometers. RESULTS: The average baseline urinary excretion of sodium and potassium was 182 mmol/24 h and 36 mmol/24 h. Baseline BP and other measured variables were similar between the potassium supplementation and placebo groups. In the active compared to the placebo treatment group, the urinary excretion of potassium was significantly increased by 20.6 mmol/24 h (P< 0.001) during 12 weeks of intervention. Compared to placebo, active treatment was associated with a significant reduction in systolic BP (-5.00 mmHg, 95% CI: -2.13 to -7.88 mmHg, P < 0.001) but not diastolic BP (-0.63 mmHg, 95% CI: -2.49 to1.23 mmHg, P = 0.51) during 12-week intervention. CONCLUSION: These data indicate that moderate potassium supplementation resulted in a substantial reduction in systolic BP. Our findings suggest that increased potassium intake may play an important role in the prevention and treatment of hypertension in China.     

Rabeprazole in nonerosive gastroesophageal reflux disease: a randomized placebo-controlled trial

OBJECTIVES: Clinical results to date suggest that antisecretory therapy may be less effective in providing symptom relief for patients with nonerosive gastroesophageal reflux disease (GERD) than for patients with erosive disease. This study was carried out to assess the efficacy and rapidity of once-daily rabeprazole (10 mg or 20 mg) in relieving symptoms in endoscopically negative patients with moderately severe GERD symptoms and to evaluate the safety of these doses over 4 wk. METHODS: This placebo-controlled, double blind study enrolled 203 men and women with moderately severe symptoms of GERD. After a 2-wk, single-blind placebo run-in phase, patients were randomized to receive 10 mg or 20 mg of rabeprazole or placebo once daily for 4 wk. RESULTS: Rabeprazole rapidly and effectively relieved heartburn, with significant improvements on day 1 of dosing. It also improved most other GERD-related symptoms, including regurgitation, belching, bloating, early satiety, and nausea. Both rabeprazole doses were significantly superior to the placebo with respect to time to the first 24-h heartburn-free interval (2.5 and 4.5 days for 10 mg and 20 mg of rabeprazole, respectively, vs 21.5 days for the placebo) and first daytime or nighttime heartburn-free interval (1.5-3 days for rabeprazole groups vs 12.5-15 days for the placebo), as well as to percentage of time patients were heartburn-free and free of antacid use. Both rabeprazole doses were well tolerated. CONCLUSIONS: Based on these findings and prior studies, rabeprazole reliably relieves GI symptoms equally well in both nonerosive GERD and erosive GERD.     

Tissue plasminogen activator: Toronto (TPAT) placebo-controlled randomized trial in acute myocardial infarction

The efficacy and safety of recombinant tissue plasminogen activator (rt-PA) administered on a dosing per weight basis was evaluated in a randomized, placebo-controlled, double-blind trial in 115 patients with acute myocardial infarction. The principal outcomes were global and regional left ventricular function in the distribution of the qualifying myocardial infarction, determined 9 days after the onset of symptoms. Global and regional ejection fraction values were significantly better for patients treated with rt-PA than for placebo-treated patients (the differences were 5.8 +/- 2.7% units [p = 0.017] and 7.1 +/- 3.1% units [p = 0.012], respectively). This benefit was also evident from visual assessment of left ventricular segmental wall motion. After adjustment for differences in important prognostic variables at baseline, the estimates of treatment effect were 4.0 +/- 2.4% units (p = 0.048) for global and 4.3 +/- 2.6% units (p = 0.047) for regional ejection fraction. Early patency of the infarct-related vessel was demonstrable in 7 (29%) of 24 placebo-treated patients and 18 (78%) of 23 rt-PA-treated patients, whereas 15 (56%) of 27 patients in the placebo group and 23 (72%) of 32 in the rt-PA group had a patent infarct-related vessel at hospital day 9. There was no significant difference in irreversible or reversible defect size as assessed by thallium scintigraphy on day 7.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.