EncephalopathyPhase 3EMBRACENCT05395195
Erythropoietin for Neonatal Encephalopathy in LMIC (EMBRACE Trial)
A Phase 3 study testing Erythropoietin and Supportive neonatal intensive care in people with Encephalopathy and Erythropoietin, run by Imperial College London at 10 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 hour to 6 hours
- Conditions the study is for
- Encephalopathy, Erythropoietin, Newborn Asphyxia
- What is being tested?
- Erythropoietin and Supportive neonatal intensive care
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 504 participants
- Where
- 10 sitesin 3 countries
- Study dates
- 31 Dec 2022to 1 Dec 2026
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 hour to 6 hours
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Inborn babies born at a gestational age greater than or equal to 36 weeks, with a birth weight >=1.8 kg
- 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.
- Moderate or severe neonatal encephalopathy on modified Sarnat staging performed between 1 to 6 hours after birth.
Who cannot join
- Imminent death at the time of recruitment
- Babies born at home or those admitted after 6 hours of birth.
- Major life-threatening congenital malformations
- Head circumference <30 cm at birth
- Babies undergoing induced hypothermia
- Migrant family or parents unable/unlikely to come back for follow-up at 18 months
- Sentinel event and encephalopathy occurred only after birth
- Unable to consent in primary language of parent(s)
Trial locations and contacts
10 sites in 3 countries. Contact the study team or a site near you to ask about taking part.
10 sites in 3 countries
India7 sites, 7 recruiting
- Recruiting
Bangalore Medical College
Bangalore
Savitha Chandraih, MD
- Recruiting
Indira Gandhi Institute of Child Health
Bangalore
Niranjan
Prathik Bandiya
- Recruiting
Institute of Child Health, Madras Medical College
Chennai
Kamal Ratnam, MD
- Recruiting
Kasturba Gandhi Medical College
Chennai
Elago, MD
Therani Rajan, MD
- Recruiting
Aurangabad Medical College
Chhatrapati Sambhajinagar
Lakshmikant Deshmukh, MD
- Recruiting
Karnataka Institute of Medical Sciences
Hubli
Sudhinedra Fattepur, MD
- Recruiting
Lokmanya Tilak Municipal Medical College
Mumbai
Swati Manerkar, MD
Thaslima Kalathingal, MD
Bangladesh2 sites, 2 recruiting
- Recruiting
Bangabandhu Sheikh Mujib Medical University
Dhaka, 1000
Mohammed Shahidullah, MD, 02 9668785, shahidullahdr@gmail.com
Sanjoy Kumar Dey, MD
- Not yet recruiting
Dhaka Medical College
Dhaka
Nazma Haque, MD
Sri Lanka1 site, 1 recruiting
- Not yet recruiting
University of Kelaniya
Kelaniya
Ranmali Rodrigo, MD, ranmali_waduge@yahoo.com
About this study
Official title: Erythropoietin Monotherapy for Brain Regeneration in Neonatal Encephalopathy in Low and Middle-Income Countries
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 when used as a mono therapy in pre-clinical models (i.e without adjunct hypothermia).
Read more
The preclinical data on combined use of Eythropoeitin and hypothermia is less convincing as the mechanisms overlap. Thus, the HEAL (High dose erythropoietin for asphyxia and encephalopathy) trial, a large phase III clinical trial involving 500 babies with with encephalopathy reported that that Erythropoietin along with hypothermia is not beneficial.
In contrast, the 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.
Read the detailed description
The burden of neonatal encephalopathy is far higher in low and middle-income countries. Recently, the Hypothermia for Encephalopathy in Low and Middle-Income Countries Trial (HELIX) study concluded cooling therapy did not reduce the combined outcome of death or disability at 18 months after neonatal encephalopathy in low-income and middle-income countries. In fact, the results found that cooling therapy significantly increased death alone. This warrants exploration of the efficacy of other treatment adjuncts for these settings.
One medication with potential for monotherapy is Erythropoietin. Erythropoietin is an erythropoiesis stimulating cytokine used for the treatment of anaemia. It is a Food and Drug Administration (FDA) approved drug that is widely used for treatment of anaemia including premature babies and has extensive safety profile in newborn babies.
Erythropoietin is also produced by neurons and glia in the hippocampus, internal capsule, cortex, and midbrain in response to hypoxia. More recently, erythropoietin has been reported as having anti-apoptotic, anti-inflammatory and anti-oxidative effects, making it a prime neuroprotective candidate. It also reduces free iron accumulation which occurs due to hypoxic ischemia by inducing erythropoiesis, which promotes neurogenesis. Extensive preclinical small and large animal models have demonstrated neuroprotective and neuro reparative effects of Erythropoietin when used as monotherapy.
A number of small randomised controlled trials have been reported from low and middle-income countries. A systematic review and meta-analysis of Erythropoietin monotherapy in babies with neonatal encephalopathy in LMIC showed pooled data including a total of 348 babies from 5 clinical trials in LMIC suggest 40% relative risk reduction (Risk Ratio 0.62 (95% Confidence Intervals (CI) 0.40 to 0.98) in death or disability at 18 months with Erythropoietin, compared with placebo. None of these clinical trials have reported any serious adverse events of Erythropoietin monotherapy.
Erythropoietin dose used in these trials varied from 300U/kg to 2500U/kg, single dose to a maximum of two weeks of duration starting within 24 hours after birth. The largest of these trials, reported from China have used a low dose (500U/kg) on alternate days for two weeks. This trial recruited 153 babies with moderate or severe encephalopathy and reported that Erythropoietin significantly reduced death or disability at 18 months.
More recently, another randomised controlled trial of Erythropoietin involving 62 normothermic babies with moderate or severe neonatal encephalopathy has been reported from Government Medical College, Aurangabad in India. The investigators used an Erythropoietin dose of 500 U/kg alternate days for 10 days starting within 24 hours. Neonatal mortality was significantly lower (39%; 12/31) in the Erythropoietin group compared with the placebo group (71%; 22/31) (p=0.01). No adverse events were reported in the Erythropoietin group.
The EMBRACE trial is a phase III, multi-country, double-blinded, placebo-controlled randomised controlled trial of Erythropoietin versus sham injection (placebo) in babies with neonatal encephalopathy in low and middle-income countries. All clinical and study team except for the nurse administering the trial drug will be masked to the intervention. The investigators plan to randomise 504 babies in this trial. The dosing regimen will be IV/Sub cutaneous Erythropoietin 500unit/kg within 6 hours of birth and then daily until 8 days. In total, there will be 9 doses. Body temperature of all babies will be monitored 4 hourly for the first three days after birth and normothermia (36.0-37.5°C) will be maintained as a part of the usual care at these hospitals with an algorithm to prevent/treat hyperthermia.
Magnetic resonance biomarkers including spectroscopy and diffusion tensor imaging will be acquired between 1 to 2 weeks of age in all recruited babies. The MR scanners and sequences at each site will be harmonised prior to recruitment.
The trial will have an 18 month recruitment period, a 18 month follow-up period, and 5 months for data analysis and write up. A pilot study (external pilot) of 50 babies will be done prior to the start of the EMBRACE trial (Jan 2023 to April 2023) but these patients will not be included in the main trial. Minor updates to the trial protocol may be made after the completion of the pilot trial.
- Conditions
- Encephalopathy, Erythropoietin, Newborn Asphyxia
- Being tested
- Erythropoietin, Supportive neonatal intensive care
- Medical subject headings
- Brain Diseases, Asphyxia Neonatorum
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ErythropoietinDrug
Erythropoietin injections (500u/kg) x 9 doses
Supportive neonatal intensive careOther
Neonatal intensive care monitoring and support including ventilatory and inotropic support as clinically indicated
| Study group | Role | What they receive |
|---|---|---|
| Erythropoietin | Experimental | Intravenous or subcutaneous injections of erythropoietin (500 U/kg/dose). Total of 9 doses will be administered. First dose will be given within 6 hours of birth. Second dose between 12 to 24 hours from the first dose. Subsequent 7 doses every 24 hours from the second dose. Receives: Drug: Erythropoietin; Other: Supportive neonatal intensive care |
| Control | Sham comparator | Mock administration of injections (pretend) behind a screen by a dedicated personal Receives: Other: Supportive neonatal intensive care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of babies who die or survive with moderate or severe disability
Death or moderate or severe disability in survivors
Measured: 18 to 22 months
Secondary outcomes (11)
Number of babies who die
Mortality from all causes
Measured: Upto 22 months
Number of babies who survive without neurodisability
Survival with Bayley composite scale scores >84 in all domains, no cerebral palsy, no seizure disorder, hearing or visual defect
Measured: 18 to 22 months
Number of babies with cerebral palsy
Cerebral palsy with a Gross Motor Function Classification Score >1
Measured: 18 to 22 months
Number of babies with microcephaly
Head circumference more than 2 standard deviations below the mean
Measured: 18 to 22 months
Number of babies with gastric bleeds
Fresh blood > 5 ml from nasogastric tube
Measured: During neonatal hospitalisation (Expected average of 2 weeks)
Number of babies with persistent pulmonary hypertension
Severe hypoxemia disproportionate to the severity of lung disease with a significant pre-and post ductal saturation difference on pulse oximetry
Measured: During neonatal hospitalisation (Expected average of 2 weeks)
Number of babies with coagulopathy
Prolonged blood coagulation requiring blood products
Measured: During neonatal hospitalisation (Expected average of 2 weeks)
Number of babies with intracranial haemorrhage
Major parenchymal or intraventricular bleed on cranial ultrasound or magnetic resonance imaging.
Measured: During neonatal hospitalisation (Expected average of 2 weeks)
Number of babies with culture-proven sepsis
Isolation of a pathogenic organism from blood or cerebrospinal fluid along with clinical evidence of sepsis or elevation of C-reactive protein
Measured: During neonatal hospitalisation (Expected average of 2 weeks)
Number of babies with severe thrombocytopenia
Platelet count of less than 25 000 per μL or less than 50 000 per μL with active bleeding
Measured: During neonatal hospitalisation (Expected average of 2 weeks)
Number of babies with abnormal neurological examination at discharge
Structured neurological examination as per the NICHD NRN trial (Shankaran et al NEJM 2005) discharge exam criteria
Measured: During neonatal hospitalisation (Expected average of 2 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 May 2022
- Study start31 Dec 2022
- Primary completion1 Dec 2024 (estimated)
- Study completion1 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for EncephalopathyStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Erythropoietin (intravenous or subcutaneous)
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 504 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sudhin Thayyil, PhD, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05395195
- Sponsor's protocol ID
- 5623613
- Acronym
- EMBRACE
- Status last verified
- Mar 2024
- First submitted
- 24 May 2022
- Last updated
- 19 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Protocol, SAP, consent forms
Publications
Ivain P, Montaldo P, Khan A, Elagovan R, Burgod C, Morales MM, Pant S, Thayyil S. Erythropoietin monotherapy for neuroprotection after neonatal encephalopathy in low-to-middle income countries: a systematic review and meta-analysis. J Perinatol. 2021 Sep;41(9):2134-2140. doi: 10.1038/s41372-021-01132-4. Epub 2021 Jun 26.
PubMed 34175900Thayyil S, Pant S, Montaldo P, Shukla D, Oliveira V, Ivain P, Bassett P, Swamy R, Mendoza J, Moreno-Morales M, Lally PJ, Benakappa N, Bandiya P, Shivarudhrappa I, Somanna J, Kantharajanna UB, Rajvanshi A, Krishnappa S, Joby PK, Jayaraman K, Chandramohan R, Kamalarathnam CN, Sebastian M, Tamilselvam IA, Rajendran UD, Soundrarajan R, Kumar V, Sudarsanan H, Vadakepat P, Gopalan K, Sundaram M, Seeralar A, Vinayagam P, Sajjid M, Baburaj M, Murugan KD, Sathyanathan BP, Kumaran ES, Mondkar J, Manerkar S, Joshi AR, Dewang K, Bhisikar SM, Kalamdani P, Bichkar V, Patra S, Jiwnani K, Shahidullah M, Moni SC, Jahan I, Mannan MA, Dey SK, Nahar MN, Islam MN, Shabuj KH, Rodrigo R, Sumanasena S, Abayabandara-Herath T, Chathurangika GK, Wanigasinghe J, Sujatha R, Saraswathy S, Rahul A, Radha SJ, Sarojam MK, Krishnan V, Nair MK, Devadas S, Chandriah S, Venkateswaran H, Burgod C, Chandrasekaran M, Atreja G, Muraleedharan P, Herberg JA, Kling Chong WK, Sebire NJ, Pressler R, Ramji S, Shankaran S; HELIX consortium. Hypothermia for moderate or severe neonatal encephalopathy in low-income and middle-income countries (HELIX): a randomised controlled trial in India, Sri Lanka, and Bangladesh. Lancet Glob Health. 2021 Sep;9(9):e1273-e1285. doi: 10.1016/S2214-109X(21)00264-3. Epub 2021 Aug 3.
PubMed 34358491Garegrat R, Londhe A, Manerkar S, Fattepur S, Deshmukh L, Joshi A, Chandriah S, Kariyappa M, Devadas S, Ethirajan T, Srivasan K, Kamalarathnam C, Balachandran A, Krishnan E, Sahayaraj D, Bandiya P, Shivanna N, Burgod C, Thayyil A, Alocious A, Lanza M, Muraleedharan P, Pant S, Venkateswaran H, Morales MM, Montaldo P, Krishnan V, Kalathingal T, Joshi AR, Vare A, Patil GC, Satyanathan BP, Hapat P, Deshmukh A, Shivarudhrappa I, Annayappa MK, Baburaj M, Muradi C, Fernandes E, Thale N, Jahan I, Shahidullah M, Choudhury SM, Dey SK, Neogi SB, Banerjee R, Rameh V, Alobeidi F, Grant E, Juul SE, Wilson M, Vita E, Pressler R, Bassett P, Shankaran S, Thayyil S. Early and extended erythropoietin monotherapy after hypoxic ischaemic encephalopathy: a multicentre double-blind pilot randomised controlled trial. Arch Dis Child Fetal Neonatal Ed. 2024 Oct 18;109(6):594-601. doi: 10.1136/archdischild-2024-327107.
PubMed 38729748
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Erythropoietin Monotherapy for Brain Regeneration in Neonatal Encephalopathy in Low and Middle-Income Countries
- ClinicalTrials.gov ID
- NCT05395195
- Acronym / sponsor ID
- EMBRACE / 5623613
- Conditions
- Encephalopathy, Erythropoietin, Newborn Asphyxia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 504 participants (estimated)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Study start
- 31 Dec 2022 (actual)
- Primary completion
- 1 Dec 2024 (estimated)
- Study completion
- 1 Dec 2026 (estimated)
- First posted
- 27 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 when used as a mono therapy in pre-clinical models (i.e without adjunct hypothermia).
The preclinical data on combined use of Eythropoeitin and hypothermia is less convincing as the mechanisms overlap. Thus, the HEAL (High dose erythropoietin for asphyxia and encephalopathy) trial, a large phase III clinical trial involving 500 babies with with encephalopathy reported that that Erythropoietin along with hypothermia is not beneficial.
In contrast, the 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.
Detailed description
The burden of neonatal encephalopathy is far higher in low and middle-income countries. Recently, the Hypothermia for Encephalopathy in Low and Middle-Income Countries Trial (HELIX) study concluded cooling therapy did not reduce the combined outcome of death or disability at 18 months after neonatal encephalopathy in low-income and middle-income countries. In fact, the results found that cooling therapy significantly increased death alone. This warrants exploration of the efficacy of other treatment adjuncts for these settings.
One medication with potential for monotherapy is Erythropoietin. Erythropoietin is an erythropoiesis stimulating cytokine used for the treatment of anaemia. It is a Food and Drug Administration (FDA) approved drug that is widely used for treatment of anaemia including premature babies and has extensive safety profile in newborn babies.
Erythropoietin is also produced by neurons and glia in the hippocampus, internal capsule, cortex, and midbrain in response to hypoxia. More recently, erythropoietin has been reported as having anti-apoptotic, anti-inflammatory and anti-oxidative effects, making it a prime neuroprotective candidate. It also reduces free iron accumulation which occurs due to hypoxic ischemia by inducing erythropoiesis, which promotes neurogenesis. Extensive preclinical small and large animal models have demonstrated neuroprotective and neuro reparative effects of Erythropoietin when used as monotherapy.
A number of small randomised controlled trials have been reported from low and middle-income countries. A systematic review and meta-analysis of Erythropoietin monotherapy in babies with neonatal encephalopathy in LMIC showed pooled data including a total of 348 babies from 5 clinical trials in LMIC suggest 40% relative risk reduction (Risk Ratio 0.62 (95% Confidence Intervals (CI) 0.40 to 0.98) in death or disability at 18 months with Erythropoietin, compared with placebo. None of these clinical trials have reported any serious adverse events of Erythropoietin monotherapy.
Erythropoietin dose used in these trials varied from 300U/kg to 2500U/kg, single dose to a maximum of two weeks of duration starting within 24 hours after birth. The largest of these trials, reported from China have used a low dose (500U/kg) on alternate days for two weeks. This trial recruited 153 babies with moderate or severe encephalopathy and reported that Erythropoietin significantly reduced death or disability at 18 months.
More recently, another randomised controlled trial of Erythropoietin involving 62 normothermic babies with moderate or severe neonatal encephalopathy has been reported from Government Medical College, Aurangabad in India. The investigators used an Erythropoietin dose of 500 U/kg alternate days for 10 days starting within 24 hours. Neonatal mortality was significantly lower (39%; 12/31) in the Erythropoietin group compared with the placebo group (71%; 22/31) (p=0.01). No adverse events were reported in the Erythropoietin group.
The EMBRACE trial is a phase III, multi-country, double-blinded, placebo-controlled randomised controlled trial of Erythropoietin versus sham injection (placebo) in babies with neonatal encephalopathy in low and middle-income countries. All clinical and study team except for the nurse administering the trial drug will be masked to the intervention. The investigators plan to randomise 504 babies in this trial. The dosing regimen will be IV/Sub cutaneous Erythropoietin 500unit/kg within 6 hours of birth and then daily until 8 days. In total, there will be 9 doses. Body temperature of all babies will be monitored 4 hourly for the first three days after birth and normothermia (36.0-37.5°C) will be maintained as a part of the usual care at these hospitals with an algorithm to prevent/treat hyperthermia.
Magnetic resonance biomarkers including spectroscopy and diffusion tensor imaging will be acquired between 1 to 2 weeks of age in all recruited babies. The MR scanners and sequences at each site will be harmonised prior to recruitment.
The trial will have an 18 month recruitment period, a 18 month follow-up period, and 5 months for data analysis and write up. A pilot study (external pilot) of 50 babies will be done prior to the start of the EMBRACE trial (Jan 2023 to April 2023) but these patients will not be included in the main trial. Minor updates to the trial protocol may be made after the completion of the pilot trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Erythropoietin (intravenous or subcutaneous)
| Arm | Type | Receives |
|---|---|---|
| Erythropoietin | Experimental | Drug: Erythropoietin, Other: Supportive neonatal intensive careIntravenous or subcutaneous injections of erythropoietin (500 U/kg/dose). Total of 9 doses will be administered. First dose will be given within 6 hours of birth. Second dose between 12 to 24 hours from the first dose. Subsequent 7 doses every 24 hours from the second dose. |
| Control | Sham comparator | Other: Supportive neonatal intensive careMock administration of injections (pretend) behind a screen by a dedicated personal |
Who may qualify
- Ages
- 1 hour to 6 hours
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Inborn babies born at a gestational age greater than or equal to 36 weeks, with a birth weight >=1.8 kg
- 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.
- Moderate or severe neonatal encephalopathy on modified Sarnat staging performed between 1 to 6 hours after birth.
Key exclusion criteria (8 listed)
- Imminent death at the time of recruitment
- Babies born at home or those admitted after 6 hours of birth.
- Major life-threatening congenital malformations
- Head circumference <30 cm at birth
- Babies undergoing induced hypothermia
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ErythropoietinErythropoietin injections (500u/kg) x 9 doses | Drug | Erythropoietin |
| Supportive neonatal intensive careNeonatal intensive care monitoring and support including ventilatory and inotropic support as clinically indicated | Other | Control, Erythropoietin |
Primary outcome
Number of babies who die or survive with moderate or severe disability
Time frame: 18 to 22 months
Death or moderate or severe disability in survivors
11 secondary outcomes
Number of babies who die
Time frame: Upto 22 months
Number of babies who survive without neurodisability
Time frame: 18 to 22 months
Number of babies with cerebral palsy
Time frame: 18 to 22 months
Number of babies with microcephaly
Time frame: 18 to 22 months
Number of babies with gastric bleeds
Time frame: During neonatal hospitalisation (Expected average of 2 weeks)
Number of babies with persistent pulmonary hypertension
Time frame: During neonatal hospitalisation (Expected average of 2 weeks)
Number of babies with coagulopathy
Time frame: During neonatal hospitalisation (Expected average of 2 weeks)
Number of babies with intracranial haemorrhage
Time frame: During neonatal hospitalisation (Expected average of 2 weeks)
Number of babies with culture-proven sepsis
Time frame: During neonatal hospitalisation (Expected average of 2 weeks)
Number of babies with severe thrombocytopenia
Time frame: During neonatal hospitalisation (Expected average of 2 weeks)
Number of babies with abnormal neurological examination at discharge
Time frame: During neonatal hospitalisation (Expected average of 2 weeks)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2024.
- Background: PubMed 34175900Ivain P, Montaldo P, Khan A, Elagovan R, Burgod C, Morales MM, Pant S, Thayyil S. Erythropoietin monotherapy for neuroprotection after neonatal encephalopathy in low-to-middle income countries: a systematic review and meta-analysis. J Perinatol. 2021 Sep;41(9):2134-2140. doi: 10.1038/s41372-021-01132-4. Epub 2021 Jun 26.
- Background: PubMed 34358491Thayyil S, Pant S, Montaldo P, Shukla D, Oliveira V, Ivain P, Bassett P, Swamy R, Mendoza J, Moreno-Morales M, Lally PJ, Benakappa N, Bandiya P, Shivarudhrappa I, Somanna J, Kantharajanna UB, Rajvanshi A, Krishnappa S, Joby PK, Jayaraman K, Chandramohan R, Kamalarathnam CN, Sebastian M, Tamilselvam IA, Rajendran UD, Soundrarajan R, Kumar V, Sudarsanan H, Vadakepat P, Gopalan K, Sundaram M, Seeralar A, Vinayagam P, Sajjid M, Baburaj M, Murugan KD, Sathyanathan BP, Kumaran ES, Mondkar J, Manerkar S, Joshi AR, Dewang K, Bhisikar SM, Kalamdani P, Bichkar V, Patra S, Jiwnani K, Shahidullah M, Moni SC, Jahan I, Mannan MA, Dey SK, Nahar MN, Islam MN, Shabuj KH, Rodrigo R, Sumanasena S, Abayabandara-Herath T, Chathurangika GK, Wanigasinghe J, Sujatha R, Saraswathy S, Rahul A, Radha SJ, Sarojam MK, Krishnan V, Nair MK, Devadas S, Chandriah S, Venkateswaran H, Burgod C, Chandrasekaran M, Atreja G, Muraleedharan P, Herberg JA, Kling Chong WK, Sebire NJ, Pressler R, Ramji S, Shankaran S; HELIX consortium. Hypothermia for moderate or severe neonatal encephalopathy in low-income and middle-income countries (HELIX): a randomised controlled trial in India, Sri Lanka, and Bangladesh. Lancet Glob Health. 2021 Sep;9(9):e1273-e1285. doi: 10.1016/S2214-109X(21)00264-3. Epub 2021 Aug 3.
- Derived from this study: PubMed 38729748Garegrat R, Londhe A, Manerkar S, Fattepur S, Deshmukh L, Joshi A, Chandriah S, Kariyappa M, Devadas S, Ethirajan T, Srivasan K, Kamalarathnam C, Balachandran A, Krishnan E, Sahayaraj D, Bandiya P, Shivanna N, Burgod C, Thayyil A, Alocious A, Lanza M, Muraleedharan P, Pant S, Venkateswaran H, Morales MM, Montaldo P, Krishnan V, Kalathingal T, Joshi AR, Vare A, Patil GC, Satyanathan BP, Hapat P, Deshmukh A, Shivarudhrappa I, Annayappa MK, Baburaj M, Muradi C, Fernandes E, Thale N, Jahan I, Shahidullah M, Choudhury SM, Dey SK, Neogi SB, Banerjee R, Rameh V, Alobeidi F, Grant E, Juul SE, Wilson M, Vita E, Pressler R, Bassett P, Shankaran S, Thayyil S. Early and extended erythropoietin monotherapy after hypoxic ischaemic encephalopathy: a multicentre double-blind pilot randomised controlled trial. Arch Dis Child Fetal Neonatal Ed. 2024 Oct 18;109(6):594-601. doi: 10.1136/archdischild-2024-327107.
- Individual participant dataSharing planned: Yes. Protocol, SAP, consent forms
Related trials for Encephalopathy
Not yet recruitingObservational study
This Multicentre Study Compares aCUP-E With Standard Electrodes During aEEG Monitoring in NICU Newborns at Risk of Encephalopathy, Assessing Recording Quality, Reliability, Ease of Use and Safety.
Encephalopathy
RecruitingPhase 2
The PROTECT-HIE Pilot Trial
Hypoxic-ischemic Encephalopathy (HIE)
RecruitingPhase 2/3
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of RLS-0071 in Newborns With Moderate or Severe Hypoxic-Ischemic Encephalopathy Undergoing Therapeutic Hypothermia
Hypoxic-Ischemic Encephalopathy
Not yet recruitingPhase 3
Open-label, Single-arm Trial of Ganaxolone in CDD Patients 6 Months to Less Than 2 Years Old
CDKL5 Deficiency Disorder
Active, not recruitingPhase 2
MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis
Mucopolysaccharidosis Disorders, Hurler Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Sudhin Thayyil, PhD principal investigator
Imperial College London
10 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Erythropoietin and Supportive neonatal intensive care in people with Encephalopathy and Erythropoietin, run by Imperial College London at 10 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 19 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in India, Bangladesh, Sri Lanka. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Reema Garegrat, DM (02033132473, r.garegrat@imperial.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of babies who die or survive with moderate or severe disability (time frame: 18 to 22 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05395195, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Mar 2024.