AI Article Synopsis
- Reltecimod, a drug that mimics the CD 28 T-lymphocyte receptor, was tested in a phase 2 clinical trial to see if early administration improves outcomes in patients with severe necrotizing soft tissue infections (NSTI).
- The study involved a randomized trial with 290 patients, comparing reltecimod to a placebo, and found significant improvements in organ dysfunction resolution and clinical outcomes for those receiving reltecimod, particularly in the per protocol analysis.
- However, while reltecimod showed better results in certain endpoints, it did not achieve statistical significance for the primary outcome when analyzing the entire population that was randomized.
Article Abstract
Background And Objective: Reltecimod, a CD 28 T-lymphocyte receptor mimetic, inhibits T-cell stimulation by an array of bacterial pathogens. A previous phase 2 trial demonstrated improved resolution of organ dysfunction after NSTI. We hypothesized that early administration of reltecimod would improve outcome in severe NSTI.
Methods: Randomized, double-blind, placebo-controlled trial of single dose reltecimod (0.5 mg/kg) administered within 6 hours of NSTI diagnosis at 65 of 93 study sites. Inclusion: surgical confirmation of NSTI and organ dysfunction [modified Sequential Organ Failure Assessment Score (mSOFA) score ≥3]. Primary analysis was modified Intent-to-Treat (mITT), responder analysis using a previously validated composite endpoint, necrotizing infection clinical composite endpoint, defined as: alive at day 28, ≤3 debridements, no amputation beyond first operation, and day 14 mSOFA ≤1 with ≥3 point reduction (organ dysfunction resolution). A prespecified, per protocol (PP) analysis excluded 17 patients with major protocol violations before unblinding.
Results: Two hundred ninety patients were enrolled, mITT (Reltecimod 142, Placebo 148): mean age 55 ± 15 years, 60% male, 42.4% diabetic, 28.6% perineal infection, screening mSOFA mean 5.5 ± 2.4. Twenty-eight-day mortality was 15% in both groups. mITT necrotizing infection clinical composite endpoint success was 48.6% reltecimod versus 39.9% placebo, P = 0.135 and PP was 54.3% reltecimod versus 40.3% placebo, P = 0.021. Resolution of organ dysfunction was 65.1% reltecimod versus 52.6% placebo, P = 0.041, mITT and 70.9% versus 53.4%, P = 0.005, PP.
Conclusion: Early administration of reltecimod in severe NSTI resulted in a significant improvement in the primary composite endpoint in the PP population but not in the mITT population. Reltecimod was associated with improved resolution of organ dysfunction and hospital discharge status.
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| http://dx.doi.org/10.1097/SLA.0000000000004102 | DOI Listing |
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