Trial Files Turns Two: Top 5 Trials Over the Past 2 Years
Restrictive or Liberal Transfusion Strategy in Myocardial Infarction and Anemia
Carson JL et al. NEJM (November 2023)
Bottom Line: This phase 3 interventional trial compared a liberal transfusion strategy (hemoglobin cutoff, <10 g/dL) to a restrictive transfusion strategy (hemoglobin cutoff, 7 or 8 g/dL) in 3504 patients with acute myocardial infarction and a hemoglobin level of less than 10 g/dL. The primary outcome was a composite of myocardial infarction or death at 30 days. The mean (±SD) number of red-cell units transfused was 0.7±1.6 in the restrictive-strategy group compared to 2.5±2.3 in the liberal-strategy group. The mean hemoglobin level was 1.3 to 1.6 g/dL lower in the restrictive-strategy group than in the liberal-strategy group on days 1 to 3 after randomization. A primary outcome event occurred in 295 of 1749 patients (16.9%) in the restrictive strategy group and in 255 of 1755 patients (14.5%) in the liberal strategy group (risk ratio modelled with multiple imputation for incomplete follow-up, 1.15; 95% confidence interval [CI], 0.99 to 1.34; P=0.07). Safety outcomes showed no significant difference in death or myocardial infarction between the two groups. The conclusion is that a liberal transfusion strategy did not significantly reduce the risk of recurrent myocardial infarction or death at 30 days, but potential harms of a restrictive transfusion strategy cannot be excluded.
Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes
Perkovic V et al. NEJM (May 2024)
Bottom line: This randomized controlled trial, with a median follow-up of 3.4 years, evaluated the efficacy and safety of subcutaneous semaglutide at a dose of 1.0 mg weekly in patients with type 2 diabetes and chronic kidney disease. The primary outcome was major kidney disease events, a composite of the onset of kidney failure (dialysis, transplantation, or an eGFR of <15 ml per minute per 1.73 m2), at least a 50% reduction in the eGFR from baseline, or death from kidney-related or cardiovascular causes. The results showed a 24% lower risk in the semaglutide group compared to the placebo group (331 vs. 410 first events; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.88; P=0.0003). Secondary outcomes, including the mean annual eGFR slope, risk of major cardiovascular events, and risk of death from any cause, also favoured semaglutide. Serious adverse events were reported in a lower percentage of participants in the semaglutide group. In conclusion, semaglutide reduced the risk of clinically important kidney outcomes and death from cardiovascular causes in this patient population.
Once-Weekly Semaglutide in Persons with Obesity and Knee Osteoarthritis
Bliddal H et al. NEJM (October 2024)
Bottom Line: This 68-week, double-blind, randomized, placebo-controlled trial evaluated the effects of once-weekly subcutaneous semaglutide (2.4 mg) on weight and pain in participants with obesity and knee osteoarthritis. A total of 407 participants were enrolled and the primary outcomes were percentage change in body weight and change in WOMAC pain score at week 68. Results showed a -13.7% change in body weight and -41.7 points change in WOMAC pain score in the semaglutide group compared to -3.2% and -27.5 points in the placebo group, respectively. Participants in the semaglutide group also had a greater improvement in SF-36 physical-function score. The incidence of serious adverse events was similar in both groups. Treatment with semaglutide resulted in significantly greater reductions in body weight and pain related to knee osteoarthritis compared to placebo.
Antibiotic Treatment for 7 versus 14 Days in Patients with Bloodstream Infections
The BALANCE Investigators. NEJM (November 2024)
Bottom Line: This multicenter, noninferiority trial included 3608 hospitalized patients with bloodstream infection who were randomly assigned to receive either 7 or 14 days of antibiotic treatment. Antibiotic selection, dosing, and route were at the discretion of the treating team. The primary outcome was death from any cause by 90 days after diagnosis, with a noninferiority margin of 4 percentage points. The results showed that 14.5% of patients receiving 7-day treatment died by 90 days, compared to 16.1% of patients receiving 14-day treatment (difference, −1.6 percentage points [95.7% confidence interval {CI}, −4.0 to 0.8]), demonstrating noninferiority of the shorter treatment duration. The study also found that patients were treated for longer than the assigned duration in 23.1% of the 7-day group and 10.7% of the 14-day group. These findings were consistent across secondary clinical outcomes and subgroups defined according to patient, pathogen, and syndrome characteristics. The conclusion is that 7-day antibiotic treatment is noninferior to 14-day treatment for hospitalized patients with bloodstream infection.
Finerenone in Heart Failure with Mildly Reduced or Preserved Ejection Fraction (FINEARTS-HF)
Solomon SD et al NEJM (September 2025)
Bottom Line: This international, double-blind trial evaluated the efficacy and safety of finerenone, a nonsteroidal mineralocorticoid receptor antagonist, in patients with heart failure and mildly reduced or preserved ejection fraction. A total of 6001 patients were randomly assigned to receive either finerenone or placebo in addition to usual therapy. The primary outcome was a composite of total worsening heart failure events and death from cardiovascular causes over a median follow-up of 32 months. Finerenone resulted in a significantly lower rate of primary outcome events compared to placebo (rate ratio, 0.84; 95% CI, 0.74 to 0.95; P = 0.007). The safety outcomes showed an increased risk of hyperkalemia and a reduced risk of hypokalemia with finerenone. In conclusion, finerenone showed efficacy in reducing the rate of primary outcome events in patients with heart failure and mildly reduced or preserved ejection fraction.
Trial Files Issue #2025-13
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