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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2013 by Hamad Medical Corporation
Sponsor:
Information provided by (Responsible Party):
Sajjad Rahman, Hamad Medical Corporation
ClinicalTrials.gov Identifier:
NCT01646619
First received: July 5, 2012
Last updated: April 3, 2013
Last verified: April 2013
  Purpose

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.


Condition Intervention Phase
Severe Hypoxic Ischemic Encephalopathy
Moderate Hypoxic Ischemic Encephalopathy
Drug: Magnesium Sulphate
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Multicenter Randomized Controlled Trial of Therapeutic Hypothermia Plus Magnesium Sulphate (MgSO4) Versus Therapeutic Hypothermia Plus Placebo in the Management of Term and Near Term Babies With Hypoxic Ischemic Encephalopathy

Resource links provided by NLM:


Further study details as provided by Hamad Medical Corporation:

Primary Outcome Measures:
  • Combined outcome of Mortality and Severe Neurodevelopmental Disability [ Time Frame: 18 - 24 months of age ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Persistent Hypotension [ Time Frame: Duration of hypothermia therapy( ie during the first 96 hours) ] [ Designated as safety issue: Yes ]
    The development of persistently low blood pressure despite adequate measures to maintain normal blood pressure will be assessed and recorded throughout the hypothermia therapy.

  • Pulmonary Hemorrhage [ Time Frame: Duration of hospital stay, an expected average of up to 4 weeks ] [ Designated as safety issue: No ]
    The development of Pulmonary hemorrhage at any stage during the patient's hospital stay will be recorded.

  • Intracranial Hemorrhage [ Time Frame: Duration of hospital stay, an expected average of up to 4 weeks ] [ Designated as safety issue: No ]
    The development of Intracranial Hemorrhage at any stage during the patient's hospital stay will be recorded by serial head ultrasounds on day 1 , day 3 and as required.

  • Pulmonary Hypertension [ Time Frame: Duration of Hypothermia therapy (ie during the first 96 hours) ] [ Designated as safety issue: No ]
    The development of pulmonary hypertension at any stage during the patient's hospital stay will be recorded.

  • Prolonged Blood Coagulation time [ Time Frame: Duration of hypothermia therapy ( ie during the first 96 hours) ] [ Designated as safety issue: No ]
    The development of abnormal coagulation profile during hypothermia therapy will be recorded.

  • Culture Proven sepsis [ Time Frame: Duration of hospital stay, an expected average of up to 4 weeks ] [ Designated as safety issue: No ]
    The development of sepsis with a positive blood culture during the patient's hospital stay will be recorded.

  • Necrotizing enterocolitis [ Time Frame: Duration of hospital stay, an expected average of up to 4 weeks ] [ Designated as safety issue: No ]
    The development of necrotizing enterocolitis during the patient's hospital stay will be recorded.

  • Cardiac Arrhythmias [ Time Frame: Duration of hypothermia therapy (ie during the first 96 hours) ] [ Designated as safety issue: No ]
    The development ofcardiac arrythmia during hypothermia therapy will be recorded.

  • Thrombocytopenia [ Time Frame: Duration of hypothermia therapy (ie during the first 96 hours) ] [ Designated as safety issue: No ]
    The development of low platelet count (<20,000) during hypothermia therapy will be recorded

  • Major venous thrombosis [ Time Frame: Duration of hospital stay, an expected average of up to 4 weeks ] [ Designated as safety issue: No ]
    The development of major venous thrombosis or a major vein thrombus during the patient's hospital stay will be recorded.

  • Renal Failure [ Time Frame: Duration of hospital stay, an expected average of up to 4 weeks ] [ Designated as safety issue: No ]
    The development of renal failure during the patient's hospital stay will be recorded

  • Abnormal liver funcion tests (elevated liver enzymes) [ Time Frame: Duration of hospital stay, an expected average of up to 4 weeks ] [ Designated as safety issue: No ]
    The devlopment of raised liver enzymes during the patient's hospital stay will be recorded.

  • Pneumonia [ Time Frame: Duration of hospital stay, an expected average of up to 4 weeks ] [ Designated as safety issue: No ]
    The development of pneumonia during the patient's hospital stay will be assessed and recorded.

  • Pulmonary air leak syndrome [ Time Frame: Duration of hospital stay, an expected average of up to 4 weeks ] [ Designated as safety issue: No ]
    The development of pulmonary air leak syndrome during the patient's hospital stay will be recorded.

  • Prolonged vs shortened hospital stay [ Time Frame: First day of NICU admission till the day of discharge, an expected average of up to 4 weeks ] [ Designated as safety issue: No ]
    The entire duration of hopital stay will be assessed

  • Neurodevelopment score [ Time Frame: On the day of discharge from hospital, an expected average of 4 weeks after admission ] [ Designated as safety issue: No ]
    A developmental paediatrician blinded to the study groups will assess the patient's neurodevlopment on the day of his or her discharge.

  • Abnormal aEEG [ Time Frame: Before randomization and during hypothermia therapy (0 hours till 96 hours) ] [ Designated as safety issue: No ]
    The aEEG is used to measure the severity of Hypoxic Ischemic Encephalopathy (moderate or severe).

  • Presence of multiple handicaps [ Time Frame: 18-24 months of age ] [ Designated as safety issue: No ]
    Multiple handicaps (( defined as the presence of any two of the following in an infant at the age of 18-24 months: neuromotor disability (level 3-5 on GMF Classification), mental delay (Bayley MDI score <70),epilepsy, cortical visual impairment, sensorineural hearing loss)).

  • Bayley Psychomotor Development Score less than 70 [ Time Frame: 18-24 months of age ] [ Designated as safety issue: No ]
  • Sensorineural hearing loss equal to, or more than, 40 dB [ Time Frame: 18-24 months of age ] [ Designated as safety issue: No ]
  • Epilepsy [ Time Frame: 18-24 months of age ] [ Designated as safety issue: No ]
    Epilepsy is defined as recurrent seizures beyond the neonatal period, requiring anticonvulsant therapy at the time of assessment

  • Microcephaly [ Time Frame: 18-24 months of age ] [ Designated as safety issue: No ]
    Defined as Head circumference more than 2 standard deviations below the mean

  • Result of EEG or MRI [ Time Frame: within the first 14 days of life ] [ Designated as safety issue: No ]
    To moniter any abnormal EEG patterns and any evidence of Ischemic/Hemorrhagic lesions on MRI


Estimated Enrollment: 300
Study Start Date: May 2012
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Hypothermia + Magnesium Sulphate Drug: Magnesium Sulphate

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

Diluent: Dextrose 5%.

Other Name: MgSo4
Placebo Comparator: Hypothermia+ Placebo Drug: Placebo
Normal Saline 0.9% Sodium Chloride is diluted in 5% Dextrose to be given as 2.5ml/kg IV q24 hrly for 3 doses.
Other Names:
  • Normal Saline
  • 0.9% Sodium Chloride

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 6 Hours
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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:

  1. Apgar score of <5 at 10 minutes after birth
  2. Continued need for resuscitation, including endotracheal or mask ventilation, at 10 minutes after birth
  3. 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)
  4. 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:

  1. hypotonia
  2. abnormal reflexes including oculomotor or pupillary abnormalities
  3. absent or weak suck
  4. 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:

  1. normal background with some seizure activity
  2. continuous seizure activity
  3. moderately abnormal activity: Only Lower border below 5 mV. upper border remains above 10mV
  4. Severely Abnormal activity (suppressed activity): Both Lower border below 5 mV and upper border below 10mV

Exclusion Criteria:

  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01646619

Contacts
Contact: Sarrah A Y Eltinay, MBBS +974-44398940 magcoolcoordinator@gmail.com
Contact: Sajjad Ur Rahman, MBBS.DCH.MCPS.FCPS.FRCPCH.FNP +974-44396123 Srahman4@hmc.org.qa

Locations
Egypt
Mansoura University Children's Hospital Recruiting
Mansoura, Egypt
Contact: Islam A Noor, MD    +20103893026    islamnoor79@yahoo.com   
Contact: Prof. Mohammed T Khashaba    +20502317925    khashabamohamed@hotmail.com   
Principal Investigator: Mohamed T Khashaba         
Malaysia
University Malaya Medical Center (UMMC) Recruiting
Kuala Lumpur, Malaysia
Contact: Lucy CS Lum, Prof    60379492065    lumcs@ummc.edu.my   
Contact: Hasimah B Zainol, Nursing    03-79492428/ 016-6217549    hasimah@ummc.edu.my   
Principal Investigator: Lucy CS Lum, Professor         
Qatar
NICU,Women's Hospital, Hamad Medical Corporation Recruiting
Doha, Qatar, 00000
Contact: Sarrah A Eltinay, MBBS    +974-44398940    magcoolcoordinator@gmail.com   
Contact: Sajjad Ur Rahman, MBBS,DCH,MCPS,FCPS,FRCPCH,FNP    +974-44396123    magcoolstudy@hotmail.com   
Sub-Investigator: Samawal Lutfi, MD, CABP, NPM (Dalhousie)         
Sub-Investigator: Hussain Parappil, MBBS,MD,DCH,FRCPCH         
Saudi Arabia
Arrayan Hospital-Dr Sulaiman Al Habib Medical Group Recruiting
Riyadh, Saudi Arabia
Contact: Jassim Anabrees, MD,MRCPCH    +96614904000 ext 9690    jasim1800@yahoo.com   
Principal Investigator: Jassim Anabress, MD         
Turkey
Zekai Tahir Burak Maternity Teaching Hospital Recruiting
Ankara, Turkey
Contact: Fuat E Canpolat, MD    +905326315185    femrecan@gmail.com   
Contact: Prof. Ugur Dilmen    +903123065267    ugurdilmen@gmail.com   
Principal Investigator: Fuat E Canpolat, MD         
Diyarbakir Children's Hospital Recruiting
Diyarbakir, Turkey
Contact: Melek Akar, MD    904122245751507    Melek_akar@yahoo.com.tr   
Contact: Heybet Tuzun, Pharm       drheybet@hotmail.com   
Principal Investigator: Melek Akar, MD         
Sub-Investigator: Heybet Tuzun, Pharm         
United Arab Emirates
Tawam Hospital Recruiting
AlAin, United Arab Emirates
Contact: Aiman Rahmani, MD    97137072181    arahmani@tawamhospital.ae   
Contact: Fares Chedid, MD    971504474661    fchedid@tawamhospital.ae   
Principal Investigator: Aiman Rahmani, MD         
Sub-Investigator: Fares Chedid, MD         
Sub-Investigator: Moghis Rehman, MD         
Sponsors and Collaborators
Sajjad Rahman
Investigators
Principal Investigator: Sajjad Ur Rahman, MBBS.DCH.MCPS.FCPS.FRCPCH.FNP Hamad Medical Corporation
  More Information

Additional Information:
Publications:

Responsible Party: Sajjad Rahman, Senior Consultant Perinatal Medicine, Hamad Medical Corporation
ClinicalTrials.gov Identifier: NCT01646619     History of Changes
Other Study ID Numbers: GC 1028A, HMC-GC1028A
Study First Received: July 5, 2012
Last Updated: April 3, 2013
Health Authority: Qatar: Hamad Medical Corporation

Keywords provided by Hamad Medical Corporation:
Hypoxic Ischemic Encephalopathy
Therapeutic Hypothermia
Therapeutic Hypothermia plus Adjuvant Therapy
Cooling

Additional relevant MeSH terms:
Brain Diseases
Brain Ischemia
Hypothermia
Hypoxia-Ischemia, Brain
Ischemia
Body Temperature Changes
Cardiovascular Diseases
Central Nervous System Diseases
Cerebrovascular Disorders
Hypoxia, Brain
Nervous System Diseases
Pathologic Processes
Signs and Symptoms
Vascular Diseases
Magnesium Sulfate
Analgesics
Anesthetics
Anti-Arrhythmia Agents
Anticonvulsants
Calcium Channel Blockers
Cardiovascular Agents
Central Nervous System Agents
Central Nervous System Depressants
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Sensory System Agents

ClinicalTrials.gov processed this record on November 23, 2014