LEVOECMO Trial Summary
Clinical Question
In adults with severe but potentially reversible cardiogenic shock on VA-ECMO, does early levosimendan improve successful ECMO weaning?
Study Design
- Multicenter, double-blind, placebo-controlled RCT across 11 French ICUs
- 205 patients were randomised within 48 hours of VA-ECMO initiation
- Levosimendan infusion 0.15 → 0.20 µg/kg/min over 24 hours vs matched placebo
- Primary outcome: Time to successful ECMO weaning within 30 days
- Key secondary outcomes: mortality (30/60d), organ-support-free days, ICU/hospital LOS, adverse events
Key Results
- Primary outcome:
- Successful weaning: 68.3% vs 68.3% (no difference) – subdistribution Hazard Ratio 1.02 (95% CI 0.74–1.39), p = 0.92
- ECMO duration: 5 vs 6 days — no difference
- Mortality:
- 30-day: 25.7% vs 22.1%
- 60-day: 27.7% vs 25.0%
- No significant differences
- Adverse events:
- Ventricular arrhythmias doubled in the Levosimendan group (17.8% vs 8.7%)
Subgroup analysis did not suggest benefit in PCCS:
- PCCS successful weaning:
- Levosimendan: 28/39 (71.8%)
- Placebo: 32/40 (80.0%)
- HR 0.73 (95% CI 0.46–1.15)
Whereas myocarditis showed a numerically favourable signal:
- Myocarditis successful weaning:
- Levosimendan: 11/12 (91.7%)
- Placebo: 10/16 (62.5%)
- HR 2.16 (95% CI 0.97–4.80)
Strengths
- Rigorous methodology: concealed randomisation, double-blind, placebo-controlled
- Standardised ECMO weaning protocol
- Competing-risk statistical approach is appropriate for ECMO studies
- High adherence to the target levosimendan dose
Limitations
- Trial underpowered due to lower-than-expected failure rate (actual 32% vs assumed 50%)
- Even so, point estimates consistently neutral
- Potential unmeasured PK alterations in ECMO patients
- Nurses preparing drugs were unblinded in phase 2 (unlikely to affect outcomes)
Interpretation
Despite decades of enthusiasm and multiple retrospective studies claiming benefit, this high-quality RCT found no advantage of levosimendan for ECMO weaning, survival, organ support, or ICU outcomes.
A clear signal of increased ventricular arrhythmias raises further concerns.
Clinical takeaway
In severe cardiogenic shock requiring VA-ECMO, levosimendan does not improve ECMO weaning or survival and increases arrhythmia risk.
Routine use for ECMO weaning is not supported by this trial.
Further questions for future study….
Should myocarditis or postcardiotomy subgroups be further studied?
What is the appropriate role of inotropes during ECMO weaning?
Reviewer: Lewis McLean
