CTRI Number	CTRI/2018/08/015369 [Registered on: 17/08/2018] Trial Registered Retrospectively
Last Modified On:	23/04/2020
Post Graduate Thesis	No
Type of Trial	Interventional
Type of Study Modification(s)	Process of Care Changes
Study Design	Randomized, Parallel Group Trial
Public Title of Study Modification(s)	Immediate skin to skin contact of the baby with mother or the surrogate
Scientific Title of Study Modification(s)	A multi-country randomized clinical trial to evaluate the impact of continuous KMC initiated immediately after birth compared to KMC initiated after stabilization in newborns with birth weight 1.0 to less than 1.8 kg on their survival in low-resource settings
Secondary IDs if Any	Secondary ID  Registry  NIL  NIL
Details of Principal Investigator or overall Trial Coordinator (multi-center study)	Name  Dr Harish Chellani  Address  Department of Pediatrics Vardhman Mahavir Medical College & Safdarjung Hospital New Delhi South DELHI 110029 India  Phone  91-11-26730241   Fax     Email  chellaniharish@gmail.com
Details Contact Person Scientific Query	Name  Dr Sugandha Arya  Address  Department of Pediatrics Vardhman Mahavir Medical College & Safdarjung Hospital New Delhi South DELHI 110029 India  Phone  91-11-26730660   Fax     Email  sugandha_arya@hotmail.com
Details Contact Person Public Query	Name  Dr Harish Chellani  Address  Department of Pediatrics Vardhman Mahavir Medical College & Safdarjung Hospital New Delhi South DELHI 110029 India  Phone  91-11-26730241   Fax     Email  chellaniharish@gmail.com
Source of Monetary or Material Support Modification(s)	Bill & Melinda Gates Foundation, 500 Fifth Avenue North Seattle, WA 98109
Primary Sponsor	Name  World Health Organization   Address  Avenue Appia 20 CH-1211 Geneva 27 Switzerland   Type of Sponsor  Other [International public health Agency]
Details of Secondary Sponsor	Name  Address  NIL  NIL
Countries of Recruitment	Ghana India Malawi Nigeria Other
Sites of Study	No of Sites = 1   Contact Person  Name of Site  Site Address  Phone/Fax/Email  Dr Harish Chellani  Vardhman Mahavir Medical College & Safdarjung Hospital  Department of Pediatrics Vardhman Mahavir Medical College & Safdarjung Hospital New Delhi 110029 South   91-11-26730241 chellaniharish@gmail.com
Details of Ethics Committee	No of Ethics Committees= 1   Name of Committee  Approval Status  Institute Ethics Committee VMMC & Safdarjung Hospital New Delhi  Approved
Regulatory Clearance Status from DCGI	Status  Not Applicable
Health Condition / Problems Studied Modification(s)	Health Type  Condition  Patients  Newborn affected by maternal conditions that may be unrelated to present pregnancy
Intervention / Comparator Agent Modification(s)	Type  Name  Details  Intervention  Immediate KMC  continuous skin-to-skin contact/ kangaroo mother care initiated immediately after birth with mother or surrogate  Comparator Agent  KMC after stabilisation  skin-to-skin contact/ kangaroo mother care initiated after stabilisation of baby with mother or surrogate
Inclusion Criteria Modification(s)	Age From  1.00 Day(s) Age To  1.00 Day(s) Gender  Both  Details  All babies born alive in the participating hospitals, with birth weight between 1.0 to less then 1.8 kg, regardless of their gestational age, are eligible for participation in this trial with their mothers. The mother-baby pair is still eligible if the mode of delivery is caesarean section, if the babies are twins or if the mother experiences some complications during labour and delivery that are expected to resolve within 3 days.
ExclusionCriteria	Details  (i) the mother is younger than 15 years of age (ii) the mother (or her guardian in case mother is a minor aged 15-17 years) is unable or unwilling to provide consent; (iii) the mother is unlikely to be able to provide KMC for the first 3 days after birth, e.g. she has eclampsia, shock or has undergone major surgery; (iv) the baby is unable to breathe spontaneously within 1 hour of birth; (v) multiple pregnancy: triplets or more; (vi) the baby has a congenital malformation that interferes with the intervention, or the intervention interferes with the required care for the congenital malformation; (vii) the place of residence is not a part of the defined study area (the study area will be defined to make 28-day follow up home visit feasible) (viii) If for any reason the mother baby pair cannot be enrolled within 2 hours of birth of the baby.
Method of Generating Random Sequence	Computer generated randomization
Method of Concealment	Pre-numbered or coded identical Containers
Blinding/Masking	Open Label
Primary Outcome	Outcome  TimePoints  Mortality   (i) mortality between enrolment and 72 hours of age, and (ii) mortality between enrolment and 28 days of age.
Secondary Outcome Modification(s)	Outcome  TimePoints  time to stabilization, hypothermia and risk of infection during hospital stay, time to hospital discharge, exclusive breastfeeding at the end of neonatal period, maternal satisfaction with care received in the hospital, and maternal depression,Time to being fully breastfed, suspected sepsis (Early onset: less than 72 hours of age, Late onset more than 72 hours of age), Probable sepsis, early or late onset, Hypoglycemia, Death in babies not enrolled in the study up to 72 hours of age.  None
Target Sample Size	Total Sample Size="4200" Sample Size from India="1680"
Phase of Trial	N/A
Date of First Enrollment (India) Modification(s)	01/12/2017
Date of First Enrollment (Global)	01/12/2017
Estimated Duration of Trial	Years="2" Months="0" Days="0"
Recruitment Status of Trial (Global) Modification(s)	Completed
Recruitment Status of Trial (India)	Completed
Publication Details Modification(s)	Study protocol published in BMC DOI: doi.org/10.1186/s13063-020-4101-1
Brief Summary Modification(s)	Aim and hypothesis: The aim of this trial is to evaluate the safety and efficacy of continuous KMC initiated immediately after birth for neonates’ with birth weight from 1.0 to <1.8 kg compared to the current recommendation of initiating continuous KMC after stabilization. The main hypothesis is that neonates with birth weight 1.0 to <1.8 kg, who are exposed to continuous KMC initiated immediately after birth, will experience a reduced risk of death compared to neonates in whom KMC is initiated after stabilization. Methods: Study design and setting: The study will be a multi-country, multi-centre, randomized controlled trial. The study will be conducted in tertiary care hospitals in five low- and middle-income countries in Asia and Sub-Saharan Africa, namely Ghana, India, Malawi, Nigeria and Tanzania. Sample size: The sample size for comparison of risk of death in intervention and control groups (21.1% compared with 16.8%) is 2080 per group, requiring a total of about 4200 neonates. Based on the number of neonates born in the selected hospitals, enrolment can be completed in about two years. For sample size calculation, we have conservatively assumed that the intervention group will have 20% lower mortality compared with control group. Population: The study population will be neonates born within the participating hospitals with birth weight between 1.0 and <1.8 kg, regardless of their gestational age. Babies will still be eligible if they are twins, or are born through caesarean section or if their mothers had delivery complications that are expected to resolve within 3 days, so that they will be able to move to the neonatal unit within 3 days of birth to provide KMC to the neonate. Triplets or quadruplets, or babies who are unable to breathe spontaneously within the first hour after birth, or who have congenital malformations that interfere with the intervention, or babies whose mothers are not able to give consent or refuse to participate in the study,  or who  live outside a defined study area will be excluded from the study. WHO statistician had prepared a computer-generated block randomization list with variable block size, stratified by site and by birth weight. The strata by birth weight will be from 1.0 to less than 1.5kg and from 1.5 to less than 1.8kg. Intervention: The intervention has three main components (i) continuous skin-to-skin contact initiated immediately after birth with mother, aiming for at least 20 hours per day; (iii) promotion and support for early exclusive breastfeeding, and (iii) provision of health care for mother and baby with as little separation as possible.  If the mother cannot provide continuous KMC for any reason, she will be asked to choose a surrogate to provide skin-to-skin contact. The intervention group will be provided continuous KMC before stabilization in the neonatal special care unit, and continuous KMC after stabilization in the KMC ward. Comparator: Neonates randomized to the control group will receive conventional care, for which the mother and baby are separated, until the baby is clinically stable. Short sessions of KMC will be started in neonates randomized to the control group when the baby is recovering but is still in the special newborn care unit. Continuous KMC will be initiated after the baby is stable and is transferred to the KMC ward. Care in both intervention and control groups: All neonates enrolled in this study will receive the WHO minimum package of care for small babies. This care will be the same for the intervention and control groups, except that babies randomized to intervention will be given continuous KMC with mothers or surrogates in the neonatal special care unit, but babies allocated to control group will receive care in incubators, radiant warmers or cots while they are unstable. Outcomes: The primary outcomes of this study will be (i) mortality between enrolment and 72 hours of age, and (ii) mortality between enrolment and 28 days of age. Secondary outcomes will be time to stabilization, hypothermia and risk of infection during hospital stay, time to hospital discharge, exclusive breastfeeding at the end of neonatal period, maternal satisfaction with care received in the hospital, and maternal depression. We will also monitor mortality in the first 72 hours of life among all live births with birth weight between 1.0 and <1.8 kg in participating hospitals, irrespective of enrolment in the trial.