Sepsis: selepressin not linked to reduced ventilator or vasopressor days

  • Laterre PF & al.
  • JAMA
  • 2 Oct 2019

  • International Clinical Digest
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Takeaway

  • For patients in septic shock, the vasopressor selepressin is not associated with improved patient-centred outcomes. 

Why this matters

  • Selepressin, a selective vasopressin V1a receptor agonist, is a noncatecholaminergic vasopressor.
  • It was hoped that the drug would avert vasodilatation, vascular leakage, and tissue edema.

Key results

  • After part 1, researchers halted trial for futility.
  • Selepressin vs placebo:
    • Ventilator- and vasopressor-free days: 15.0 vs 14.5;
      • Difference, 0.6 (95% CI, −1.3 to 2.4) days (P=.30).
    • 90-day all-cause mortality: 40.6% vs 39.4%;
      • Difference, 1.1% (95% CI, −6.5% to 8.8%; P=.77).
    • 30-day renal replacement therapy-free days: 18.5 vs 18.2;
      • Difference, 0.29 (95% CI, −2.1 to 2.6) days (P=.85).
    • 30-day ICU-free days: 12.6 vs 12.2;
      • Difference, 0.49 (95% CI, −1.2 to 2.2) days (P=.41).
  • Selepressin group also had higher mean arterial pressure, less cardiovascular dysfunction, and more new-onset coagulopathies.

Study design

  • Multinational, adaptive, phase 2b/3 randomized SEPSIS-ACT trial (n=828).
  • In part 1, adults with septic shock and norepinephrine requirement were randomly allocated to 1 of 3 selepressin dosing regimens vs placebo.
  • In part 2 (canceled), best-performing selepressin regimen was to be compared with placebo. 
  • Outcome: ventilator- and vasopressor-free days within 30 days.
  • Funding: Ferring Pharmaceuticals A/S.

Limitations

  • Patients had a median 8 hours of preenrollment norepinephrine.
  • Limited ability to assess subgroup/treatment interactions.