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Randomized Controlled Trial
. 2024 Oct 18;109(6):594-601.
doi: 10.1136/archdischild-2024-327107.

Early and extended erythropoietin monotherapy after hypoxic ischaemic encephalopathy: a multicentre double-blind pilot randomised controlled trial

Reema Garegrat  1 , Atul Londhe  2 , Swati Manerkar  3 , Sudhindrashayana Fattepur  4 , Laxmikant Deshmukh  2 , Amol Joshi  2 , Savitha Chandriah  5 , Mallesh Kariyappa  6 , Sahana Devadas  6 , Theranirajan Ethirajan  7 , Kalaivani Srivasan  7 , Chinnathambi Kamalarathnam  7 , Anitha Balachandran  7 , Elango Krishnan  7 , Deepthy Sahayaraj  7 , Prathik Bandiya  8 , Niranjan Shivanna  9 , Constance Burgod  10 , Ashwini Thayyil  11 , Annie Alocious  10 , Marianna Lanza  10 , Pallavi Muraleedharan  10 , Stuti Pant  10 , Harini Venkateswaran  12 , Maria Moreno Morales  10 , Paolo Montaldo  10 , Vaisakh Krishnan  10 , Thaslima Kalathingal  13 , Anagha Rajeev Joshi  13 , Ajay Vare  2 , G C Patil  14 , Babu Peter Satyanathan  7 , Pavan Hapat  12 , Abhishek Deshmukh  12 , Indramma Shivarudhrappa  12 , Manjesh Kurupalya Annayappa  5 , Mythili Baburaj  12 , Christina Muradi  12 , Esprance Fernandes  12 , Nishad Thale  12 , Ismat Jahan  15 , Mohammed Shahidullah  15 , Sadeka Moni Choudhury  15 , Sanjoy Kumer Dey  15 , Sutapa B Neogi  16 , Rupsa Banerjee  16 , Vanessa Rameh  17 , Farah Alobeidi  18 , Ellen Grant  17 , Sandra E Juul  19 , Martin Wilson  20 , Enrico De Vita  21 , Ronit Pressler  11 , Paul Bassett  22 , Seetha Shankaran  23 , Sudhin Thayyil  10
Affiliations
Randomized Controlled Trial

Early and extended erythropoietin monotherapy after hypoxic ischaemic encephalopathy: a multicentre double-blind pilot randomised controlled trial

Reema Garegrat et al. Arch Dis Child Fetal Neonatal Ed. .

Abstract

Objective: To examine the feasibility of early and extended erythropoietin monotherapy after hypoxic ischaemic encephalopathy (HIE).

Design: Double-blind pilot randomised controlled trial.

Setting: Eight neonatal units in South Asia.

Patients: Neonates (≥36 weeks) with moderate or severe HIE admitted between 31 December 2022 and 3 May 2023.

Interventions: Erythropoietin (500 U/kg daily) or to the placebo (sham injections using a screen) within 6 hours of birth and continued for 9 days. MRI at 2 weeks of age.

Main outcomes and measures: Feasibility of randomisation, drug administration and assessment of brain injury using MRI.

Results: Of the 154 neonates screened, 56 were eligible; 6 declined consent and 50 were recruited; 43 (86%) were inborn. Mean (SD) age at first dose was 4.4 (1.2) hours in erythropoietin and 4.1 (1.0) hours in placebo. Overall mortality at hospital discharge occurred in 5 (19%) vs 11 (46%) (p=0.06), and 3 (13%) vs 9 (40.9%) (p=0.04) among those with moderate encephalopathy in the erythropoietin and placebo groups. Moderate or severe injury to basal ganglia, white matter and cortex occurred in 5 (25%) vs 5 (38.5%); 14 (70%) vs 11 (85%); and 6 (30%) vs 2 (15.4%) in the erythropoietin and placebo group, respectively. Sinus venous thrombosis was seen in two (10%) neonates in the erythropoietin group and none in the control group.

Conclusions: Brain injury and mortality after moderate or severe HIE are high in South Asia. Evaluation of erythropoietin monotherapy using MRI to examine treatment effects is feasible in these settings.

Trial registration number: NCT05395195.

Keywords: Global Health; Intensive Care Units, Neonatal; Magnetic Resonance Imaging; Neonatology; Neurology.

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Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1
Figure 1. Flow chart.
Figure 2
Figure 2. (A) Evolution of encephalopathy in erythropoietin (Epo) and placebo groups (Plc). (B) Survival up to 6 months among the Epo (blue) and the Plc (red) groups.
Figure 3
Figure 3. Neonate A: T1-weighted axial (A1, A2) and sagittal (A3) images and T2-weighted (A4, A5) axial MRIs of the brain at 10 days of age in a term infant with moderate HIE who received erythropoietin. White arrows indicate extensive thrombosis in sagittal sinus, right transverse sinus and cortical veins. Repeat MRI at 6 months showed normal T1-weighted axial (AR1, AR2) and sagittal MR scans (AR3), MR venography (AR4) and T2-weighted axial scan (AR5). Neonate B: T1-weighted axial (B1, B2) and sagittal (B3) and maximal intensity projection (B4) and T2-weighted axial (B5) MRIs of the brain at 20 days of age in a term infant with moderate HIE who received erythropoietin. White arrows denote expansion with T1 shortening and loss of the normal flow void at the level of the transverse sinuses (right greater than left) and inferior aspect of the torcula. Red arrows indicate punctate white matter injury. HIE, hypoxic ischaemic encephalopathy.
See this image and copyright information in PMC

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