Efficacy Study of Hypothermia Plus Magnesium Sulphate(MgSO4) in the Management of Term and Near Term Babies With Hypoxic Ischemic Encephalopathy

NCT01646619 | Unknown Phase 3 DMC

• 2 other identifiers: GC 1028AHMC-GC1028A
• Study Type: interventional
• Target: 300
• Locations: 6 countries
• Sites: 7

Brief Summary

The purpose of this study is to assess whether the addition of a drug such as Magnesium sulphate while providing therapeutic hypothermia (or cooling) to babies who are asphyxiated at birth provides additional benefit to the babies' survival and outcome compared to cooling alone.

Conditions

Severe Hypoxic Ischemic Encephalopathy; Moderate Hypoxic Ischemic Encephalopathy

Keywords

Hypoxic Ischemic Encephalopathy; Therapeutic Hypothermia; Therapeutic Hypothermia plus Adjuvant Therapy; Cooling

Outcome Measures

Primary Outcomes (1)

• Combined outcome of Mortality and Severe Neurodevelopmental Disability

  Severe Neurodevelopmental Disability will be assessed at discharge from hospital and at 18-24 months of age to assess developmental delay and cerebral palsy using the Bayley Scale of Infant Development II.

  18 - 24 months of age

Secondary Outcomes (23)

• Persistent Hypotension

  Duration of hypothermia therapy( ie during the first 96 hours)

• Pulmonary Hemorrhage

  Duration of hospital stay, an expected average of up to 4 weeks

• Intracranial Hemorrhage

  Duration of hospital stay, an expected average of up to 4 weeks

• Pulmonary Hypertension

  Duration of Hypothermia therapy (ie during the first 96 hours)

• Prolonged Blood Coagulation time

  Duration of hypothermia therapy ( ie during the first 96 hours)

Study Arms (2)

Hypothermia + Magnesium Sulphate

ACTIVE COMPARATOR

Drug: Magnesium Sulphate

Hypothermia+ Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Magnesium Sulphate DRUG

10% MgSo4 (100mg/ml) given in a dose of 250mg/kg IV q 24 hrly for 3 doses(2.5ml/kg). Diluent: Dextrose 5%.

Also known as: MgSo4

Hypothermia + Magnesium Sulphate

Placebo DRUG

Normal Saline 0.9% Sodium Chloride is diluted in 5% Dextrose to be given as 2.5ml/kg IV q24 hrly for 3 doses.

Also known as: Normal Saline, 0.9% Sodium Chloride

Hypothermia+ Placebo

Eligibility Criteria

• Age: Up to 6 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• The babies will be assessed sequentially by criteria A, B and C listed below:
• A. Evidence of Perinatal Asphyxia at birth: Infants ≥35 completed weeks gestation admitted to the NICU with at least one of the following:
• Apgar score of \<5 at 10 minutes after birth
• Continued need for resuscitation, including endotracheal or mask ventilation, at 10 minutes after birth
• Acidosis within 60 minutes of birth (defined as any occurrence of umbilical cord arterial or venous pH \<7.00 or otherwise arterial or capillary pH \<7.00)
• Base Deficit (-16 mmol/L or more) in umbilical cord or any blood sample (arterial, venous or capillary) within 60 minutes of birth
• Infants that meet criteria A will be assessed for whether they meet the neurological abnormality entry criteria (B) by trained personnel:
• B. Clinical Evidence of Moderate to severe encephalopathy, consisting of altered state of consciousness (lethargy, stupor or coma) AND at least one of the following:
• hypotonia
• abnormal reflexes including oculomotor or pupillary abnormalities
• absent or weak suck
• clinical seizures
• Infants who meet criteria A \& B will be assessed by aEEG only in units where facility for Cerebral Function Monitoring (CFM) is available.
• C. (Optional) At least 30 minutes duration of amplitude integrated EEG recording that shows abnormal background aEEG activity or seizures. There must be one of the following:
• normal background with some seizure activity

You may not qualify if:

• Infants expected to be \> 6 hours of age at the time of randomization.Every effort will be made to ensure entry to the study before 3 hours of age.
• Major congenital abnormalities, such as diaphragmatic hernia requiring ventilation, or congenital abnormalities suggestive of chromosomal anomaly or other syndromes that includes brain dysgenesis.

Sponsors & Collaborators

• Sajjad Rahman: lead

Study Sites (7)

Mansoura University Children's Hospital

Al Mansurah, Egypt

RECRUITING

University Malaya Medical Center (UMMC)

Kuala Lumpur, Malaysia

RECRUITING

NICU,Women's Hospital, Hamad Medical Corporation

Doha, Baladīyat ad Dawḩah, 00000, Qatar

RECRUITING

Arrayan Hospital-Dr Sulaiman Al Habib Medical Group

Riyadh, Riyadh Region, Saudi Arabia

RECRUITING

Zekai Tahir Burak Maternity Teaching Hospital

Ankara, Turkey (Türkiye)

RECRUITING

Diyarbakir Children's Hospital

Diyarbakır, Turkey (Türkiye)

RECRUITING

Tawam Hospital

AlAin, United Arab Emirates

RECRUITING

Related Publications (15)

• Paul VK. Neonatal morbidity and mortality: report of the national neonatal and perinatal database. Indian Pediatr. 1999 Feb;36(2):167-9. No abstract available.

  PMID: 10713810 BACKGROUND

• Bhat MA, Shah ZA, Makhdoomi MS, Mufti MH. Theophylline for renal function in term neonates with perinatal asphyxia: a randomized, placebo-controlled trial. J Pediatr. 2006 Aug;149(2):180-4. doi: 10.1016/j.jpeds.2006.03.053.

  PMID: 16887430 BACKGROUND

• Paneth N. The causes of cerebral palsy. Recent evidence. Clin Invest Med. 1993 Apr;16(2):95-102.

  PMID: 8513618 BACKGROUND

• Dixon G, Badawi N, Kurinczuk JJ, Keogh JM, Silburn SR, Zubrick SR, Stanley FJ. Early developmental outcomes after newborn encephalopathy. Pediatrics. 2002 Jan;109(1):26-33. doi: 10.1542/peds.109.1.26.

  PMID: 11773538 BACKGROUND

• Edwards AD, Azzopardi DV. Hypothermic neural rescue: work continues. J Pediatr. 2010 Sep;157(3):351-2. doi: 10.1016/j.jpeds.2010.06.029. Epub 2010 Jul 24. No abstract available.

  PMID: 20659738 BACKGROUND

• Gluckman PD, Wyatt JS, Azzopardi D, Ballard R, Edwards AD, Ferriero DM, Polin RA, Robertson CM, Thoresen M, Whitelaw A, Gunn AJ. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet. 2005 Feb 19-25;365(9460):663-70. doi: 10.1016/S0140-6736(05)17946-X.

  PMID: 15721471 BACKGROUND

• Azzopardi DV, Strohm B, Edwards AD, Dyet L, Halliday HL, Juszczak E, Kapellou O, Levene M, Marlow N, Porter E, Thoresen M, Whitelaw A, Brocklehurst P; TOBY Study Group. Moderate hypothermia to treat perinatal asphyxial encephalopathy. N Engl J Med. 2009 Oct 1;361(14):1349-58. doi: 10.1056/NEJMoa0900854.

  PMID: 19797281 BACKGROUND

• Simbruner G, Mittal RA, Rohlmann F, Muche R; neo.nEURO.network Trial Participants. Systemic hypothermia after neonatal encephalopathy: outcomes of neo.nEURO.network RCT. Pediatrics. 2010 Oct;126(4):e771-8. doi: 10.1542/peds.2009-2441. Epub 2010 Sep 20.

  PMID: 20855387 BACKGROUND

• Zhou WH, Cheng GQ, Shao XM, Liu XZ, Shan RB, Zhuang DY, Zhou CL, Du LZ, Cao Y, Yang Q, Wang LS; China Study Group. Selective head cooling with mild systemic hypothermia after neonatal hypoxic-ischemic encephalopathy: a multicenter randomized controlled trial in China. J Pediatr. 2010 Sep;157(3):367-72, 372.e1-3. doi: 10.1016/j.jpeds.2010.03.030. Epub 2010 May 20.

  PMID: 20488453 BACKGROUND

• Levene MI. Cool treatment for birth asphyxia, but what's next? Arch Dis Child Fetal Neonatal Ed. 2010 May;95(3):F154-7. doi: 10.1136/adc.2009.165738. No abstract available.

  PMID: 20444808 BACKGROUND

• Jacobs S, Hunt R, Tarnow-Mordi W, Inder T, Davis P. Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD003311. doi: 10.1002/14651858.CD003311.pub2.

  PMID: 17943788 BACKGROUND

• Edwards AD, Brocklehurst P, Gunn AJ, Halliday H, Juszczak E, Levene M, Strohm B, Thoresen M, Whitelaw A, Azzopardi D. Neurological outcomes at 18 months of age after moderate hypothermia for perinatal hypoxic ischaemic encephalopathy: synthesis and meta-analysis of trial data. BMJ. 2010 Feb 9;340:c363. doi: 10.1136/bmj.c363.

  PMID: 20144981 BACKGROUND

• Rutherford M, Ramenghi LA, Edwards AD, Brocklehurst P, Halliday H, Levene M, Strohm B, Thoresen M, Whitelaw A, Azzopardi D. Assessment of brain tissue injury after moderate hypothermia in neonates with hypoxic-ischaemic encephalopathy: a nested substudy of a randomised controlled trial. Lancet Neurol. 2010 Jan;9(1):39-45. doi: 10.1016/S1474-4422(09)70295-9. Epub 2009 Nov 5.

  PMID: 19896902 BACKGROUND

• Rouse DJ, Hirtz DG, Thom E, Varner MW, Spong CY, Mercer BM, Iams JD, Wapner RJ, Sorokin Y, Alexander JM, Harper M, Thorp JM Jr, Ramin SM, Malone FD, Carpenter M, Miodovnik M, Moawad A, O'Sullivan MJ, Peaceman AM, Hankins GD, Langer O, Caritis SN, Roberts JM; Eunice Kennedy Shriver NICHD Maternal-Fetal Medicine Units Network. A randomized, controlled trial of magnesium sulfate for the prevention of cerebral palsy. N Engl J Med. 2008 Aug 28;359(9):895-905. doi: 10.1056/NEJMoa0801187.

  PMID: 18753646 BACKGROUND

• Bhat MA, Charoo BA, Bhat JI, Ahmad SM, Ali SW, Mufti MU. Magnesium sulfate in severe perinatal asphyxia: a randomized, placebo-controlled trial. Pediatrics. 2009 May;123(5):e764-9. doi: 10.1542/peds.2007-3642. Epub 2009 Apr 6.

  PMID: 19349375 BACKGROUND

MeSH Terms

Conditions

Hypoxia-Ischemia, Brain

Interventions

Magnesium Sulfate; Saline Solution; Sodium Chloride

Condition Hierarchy (Ancestors)

Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hypoxia, Brain; Vascular Diseases; Cardiovascular Diseases; Hypoxia; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Magnesium Compounds; Inorganic Chemicals; Sulfates; Sulfuric Acids; Sulfur Acids; Sulfur Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Chlorides; Hydrochloric Acid; Chlorine Compounds; Sodium Compounds

Study Officials

• Sajjad Ur Rahman, MBBS.DCH.MCPS.FCPS.FRCPCH.FNP

  Hamad Medical Corporation

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sarrah A Y Eltinay, MBBS

CONTACT

+974-44398940; magcoolcoordinator@gmail.com

Sajjad Ur Rahman, MBBS.DCH.MCPS.FCPS.FRCPCH.FNP

CONTACT

+974-44396123; Srahman4@hmc.org.qa

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Senior Consultant Perinatal Medicine

Study Record Dates

• First Submitted: July 5, 2012
• First Posted: July 20, 2012
• Study Start: May 1, 2012
• Primary Completion: December 1, 2013
• Study Completion: June 1, 2014
• Last Updated: April 4, 2013

Record last verified: 2013-04

Locations

AE (1); EG (1); MY (1); SA (1); TU (2); QA (1)