Erythropoietin for Neonatal Encephalopathy in LMIC (EMBRACE Trial)

• Status: Not yet recruiting
• Trial end date: 2026-12-01
• Target enrollment: 0
• Participant gender: All

Summary

One million babies die, and at least 2 million survive with lifelong disabilities following neonatal encephalopathy (NE) in low and middle-income countries (LMICs), every year. Cooling therapy in the context of modern tertiary intensive care improves outcome after NE in high-income countries. However, the uptake and applicability of cooling therapy in LMICs is poor, due to the lack of intensive care and transport facilities to initiate and administer the treatment within the six-hours window after birth as well as the absence of safety and efficacy data on hypothermia for moderate or severe NE.

Erythropoietin (Epo) is a promising neuroprotectant with both acute effects (anti-inflammatory, anti-excitotoxic, antioxidant, and antiapoptotic) and regenerative effects (neurogenesis, angiogenesis, and oligodendrogenesis),which are essential for the repair of injury and normal neurodevelopment. Pooled data from 5 small randomized clinical trials (RCTs) (n=348 babies), suggests that Epo (without cooling therapy) reduce the risk of death or disability at 3 months or more after NE (Risk Ratio 0.62 (95% CI 0.40 to 0.98). Hence, a definitive trial (phase III) for rigorous evaluation of the safety and efficacy of Epo monotherapy in LMIC is now warranted.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Thayyil, Sudhin
• Treatments: Epoetin Alfa

Criteria

Inclusion Criteria:

All inborn babies born at a gestational age > 36 weeks, with a birth weight >2kg will be screened for eligibility and recruited if they meet the inclusion criteria.

Inclusion criteria (Both A and B required) A. At least one of the following: need for continued resuscitation at 5 minutes of age; 5-minute Apgar score < 6; metabolic acidosis (pH < 7.0; base deficit > 16 mmol/L) in cord or blood gas within the first hour of birth.

B. Moderate or severe neonatal encephalopathy on modified Sarnat staging performed between 1 to 3 hours after birth.

Exclusion Criteria:

(i) Imminent death at the time of recruitment (ii) Babies born at home or those admitted after 3 hours of birth. (iii) Major life-threatening congenital malformations (iv) Head circumference <30 cm at birth (v) Polycythaemia with a venous haematocrit >65% at the time of recruitment (vi) Babies undergoing therapeutic hypothermia (vii) Migrant family or parents unable/unlikely to come back for follow-up at 18 months (viii) Sentinel event and encephalopathy occurred only after birth (ix) Unable to consent in primary language of parent(s)