Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618001880235
Ethics application status
Approved
Date submitted
10/09/2018
Date registered
19/11/2018
Date last updated
7/04/2021
Date data sharing statement initially provided
19/11/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Effect of immediate Kangaroo Mother Care on neonatal mortality for mothers and babies
Scientific title
A multi-country randomized clinical trial to evaluate the impact of continuous Kangaroo Mother Care (KMC) initiated as soon as possible after birth, compared to KMC initiated after stabilization in newborns with birth weight 1.0 to <1.8 kg on their survival in low-resource settings.
Secondary ID [1] 295846 0
Nil known
Universal Trial Number (UTN)
U1111-1219-1230
Trial acronym
I-KMC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
low birth weight 309296 0
Condition category
Condition code
Reproductive Health and Childbirth 308169 308169 0 0
Complications of newborn

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention is Kangaroo Mother Care (KMC) for low birth weight (LBW) babies >1 kg and < 1.8 kg starting as soon as possible after birth. The intervention has three main components:
(i) promotion and support for continuous skin-to-skin contact initiated as soon as possible after birth with a mother or a surrogate, aiming for at least 20 hours per day, which is continued during entire hospital stay. Continuous KMC before stabilization will be provided in the neonatal special care unit, and continuous KMC after stabilization in the KMC ward.
(ii) promotion and support for early exclusive breastfeeding during hospital stay, and
(iii) provision of health care for mother and baby with as little separation as possible during hospital stay.

WHO manual on Kangaroo Mother Care, and specifically desgined training manuals for immediate KMC are used. Face to face counselling on KMC is provided to mothers/surrogates by KMC supporters as long as mother feels they need the counselling. Counselling includes explanation and demonstration of the method of providing skin to skin contact, the importance of KMC to the baby and ways to comfortably provide KMC. The most important factor for successful implementation of the intervention is keeping the mother comfortable. This includes among other things, taking care of her pain, comfortable bed, toilet, food and water, and a soothing environment. Breastfeeding support includes counselling on the importance of early and exclusive breastfeeding, and support for appropriate positioning and attachment. The worker also counsels the mother on how to cope with the fact that she has had a low birth weight baby.

Immediate KMC is delivered by the paediatrician/neonatologist, nurses, and KMC support workers. Immediate KMC period is from randomization to stabilization while the baby is in SNCU. Minimum period is 24 hours and extends upto the time baby is shifted out of SNCU.

In the intervention group, the mother and baby will remain in skin-to-skin contact from the time of randomization. The mother and baby will be provided health care in KMC position as much as possible. Mothers will be provided health care by obstetric staff while she is in the neonatal unit. If a mother has any complication for which she needs to be transferred to the postnatal ward, intensive care unit or operation theatre, skin-to-skin contact will be continued with a surrogate. If the baby requires a procedure or treatment that is not possible in skin-to-skin contact, the baby will be shifted to a cot or radiant warmer. skin-to-skin contact will be temporarily interrupted for the period of the procedure or treatment, and recommenced as soon as possible after that.

If both the mother and surrogate are temporarily not available to provide KMC in the SCNU, the baby will be kept in a cot, incubator or radiant warmer as required.


To monitor the compliance with intervention a daily sheet is completed by the KMC support workers in the SCNU and KMC ward. This sheet has an hourly record of duration of skin-to-skin contact with the mother or the surrogate, and the period of separation. This includes the brief KMC sessions that control group babies may receive in the SCNU. The number of times the baby is put to the breast is also recorded. At the home visit on day 29, mothers is asked if KMC was continued after discharge from hospital.
Intervention code [1] 312183 0
Treatment: Other
Comparator / control treatment
Neonates randomized to the control group will receive conventional care, for which the mother and baby are separated, UNTIL the baby is clinically stable. During this early period, control group neonates will not receive any KMC. Short sessions of KMC will be started in these neonates when the baby is recovering but is still in the newborn special care unit. Continuous KMC will only be initiated after the baby is stable and is transferred to the KMC ward, based on pre-specified criteria.
Control group
Active

Outcomes
Primary outcome [1] 307136 0
Mortality between enrolment and 72 hours of age
Timepoint [1] 307136 0
Enrolment to 72 hours of age
Primary outcome [2] 307779 0
Mortality between enrolment and 28 days of age.
Timepoint [2] 307779 0
Enrolment to 28 days of age
Secondary outcome [1] 350806 0
Exclusive breastfeeding (or exclusive breast milk feeding) at the end of the neonatal period.
(measured through a 24 hour feeding recall at a home visit)
Timepoint [1] 350806 0
On day 29 of age.
Secondary outcome [2] 352231 0
Time to being fully breastfed.
(Age at which the baby could feed fully by suckling on the breast, without requiring any feeding by cup or nasogastric tube).
Timepoint [2] 352231 0
The mode of feeding is recorded every 12 hours from birth till discharge from the hospital.
Secondary outcome [3] 352232 0
Suspected sepsis

(Sepsis will be suspected when a baby has clinical deterioration after initial improvement. This includes stopped feeding well after starting to feed, increase in respiratory distress after initial improvement, lethargy after improvement in activity, fever, or hypothermia after baby started maintaining temperature (not associated with environment hypothermia or with hypoglycemia).
Timepoint [3] 352232 0
The subjects are monitored for clinical signs of sepsis every 12 hours during hospital stay.
Secondary outcome [4] 352239 0
Probable sepsis

(If criteria for suspected sepsis are met, plus a positive laboratory screening test (high or low neutrophil percentage and count or positive C-Reactive Protein), it is considered as "probable sepsis.
Timepoint [4] 352239 0
The subjects are monitored for clinical signs of sepsis every 12 hours during hospital stay.
Secondary outcome [5] 352240 0
Hypothermia

Axillary temperature is measured by a research assistant every 6 hours using a thermometer, and the measurement is recorded in a monitoring sheet.
Timepoint [5] 352240 0
Temperature is recorded at least every 12 hours during hospital stay.

Secondary outcome [6] 352241 0
Hypoglycemia

Blood sugar will be monitored every 6 hours during the first 24 hours after birth using blood glucose test strips. This will be recorded in the hospital follow up form every 12 hours. In addition, any hypoglycemia recorded in between the routine scheduled evaluations or beyond the first 24 hours based on the clinical condition of the baby will also be noted in the hospital follow up form.
Timepoint [6] 352241 0
Glucose is measured at 6, 12, 18 and 24 hours of age, or at any time during hospital stay if needed.

Secondary outcome [7] 352242 0
Time to clinical stabilization

(The time to clinical stabilisation is considered as the age at which the baby is considered to be clinically stable. The following criteria for stability should be met for at least a continuous period of 24 hours:
(i) Respiratory rate 40-60/min
(ii) No apnoea
(iii) No need for CPAP
(iv) SpO2 on room air >90%
(v) Heart rate 80-160/min
(vi) Axillary temperature 36-37.4°C
(vii) No need for IV fluids)

Above outcomes are measured every 6 hours by research assistant and recorded in the daily monitoring sheet. Respiratory rate is assessed based on clinical assessment. Assessment of apnoea is based on the reporting by a mother or a surrogate, or based on the observation by nurses.

Need for CPAP and IV fluids are determined by clinical judgement of treating physician. SpO2 and heart rate are assessed by pulse oximeters, and auxiliary temperature is by thermometers.
Timepoint [7] 352242 0
Clinical signs and health care recorded every 12 hours during hospital stay
Secondary outcome [8] 352244 0
Maternal satisfaction with health care in the hospital

Maternal satisfaction with health care received by the mother and baby is assessed by a questionnaire designed specifically for this study.
Timepoint [8] 352244 0
Questionnaire is given to the mother after transfer to KMC ward, and around the time of discharge from the hospital. This questionnaire assesses the satisfaction with health care received by the mother and baby.
Secondary outcome [9] 352245 0
Maternal depression
Timepoint [9] 352245 0
Patient Health Questionnaire 9 (PHQ-9) is administered to mothers at the day 29 home visit. A score of 15 points or more is considered as maternal depression.

Eligibility
Key inclusion criteria
All mothers and their newborn babies born alive in the participating hospitals, with birth weight between 1.0 kg to less then 1.8 kg, regardless of their gestational age.
Minimum age
0 Hours
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Among those who meet inclusion criteria, the following will be excluded:
(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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
The random allocation is concealed in serially numbered, opaque, sealed envelopes prepared at WHO and sent to sites.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer-generated block randomization list with variable block size, stratified by site and by birth weight, prepared at WHO. The birth weight strata will be (1) 1.0 to <1.5kg, and (2) 1.5 to <1.8kg.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
The primary analysis will be executed by intention to treat. Even if the KMC is discontinued because of clinical conditions of the mother, the neonate will not be excluded. Effect size will be estimated with comparison of intervention and comparison group mortality risks. The two primary outcomes are complementary, so adjustment for type I error is not needed. Results will be reported using CONSORT statement. A detailed analysis plan will be developed and published as part of the methods paper before the end of data collection.

Baseline characteristics will be presented by group to describe the study population and to check the success of randomization. Descriptors will be summarized as means and standard deviations for continuous variables; and frequencies and percentages for categorical variables. In case there are important differences in some of the baseline characteristics, results adjusted for these characteristics will be presented.

Effect sizes and their 95% confidence intervals will be calculated for the primary outcomes. Significance tests with 5% significance level will be performed and p values will be reported. If loss to follow up for primary outcomes is below 2.5% for mortality, we will calculate risk ratios and their confidence intervals. If loss to follow up for primary outcomes is greater than 2.5%, Hazards Ratios and their confidence intervals will be calculated. If important differences in baseline characteristics between intervention and control groups are identified, multiple logistic regression or Cox proportional hazards models will be used to adjust for confounding.

Subgroup analysis will be conducted for the two mortality outcomes by: (1) birth weight categories, 1.0 to <1.2, 1.2 to <1.5 and 1.5 to <1.8 kg, (2) gestational age at birth categories,<31, 31 to <34, 34 to <37 weeks, and (3) singleton or multiple births (4) small for gestational age or not (5) by mode of delivery i.e. normal vaginal delivery or cesarean section. Statistical tests of interaction will be used to interpret if the effect sizes in the categories are different or similar.

A secondary analysis stratified by compliance to Immediate KMC over 72 hours of age will be done. This analysis will report on efficacy of the intervention by average duration of skin-to-skin contact, classified as >20 hours/day; 10-19 hours/day; and <10 hours/day. In this secondary analysis, reverse causality may be an important issue because severely ill newborns may receive less or no skin-to-skin contact.

To reduce the possibility of reverse causality, in a sub-analysis we will exclude the babies who show signs of severe illness in the first 6 hours of life.

Recruitment
Recruitment status
Stopped early
Data analysis
Data analysis is complete
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
The DSMB recommended stopping further enrolment in the trial because of clear benefit in neonatal mortality reduction.
Date of first participant enrolment
Anticipated
Actual
1/12/2017
Date of last participant enrolment
Anticipated
31/08/2020
Actual
20/01/2020
Date of last data collection
Anticipated
30/09/2020
Actual
19/02/2020
Sample size
Target
4200
Accrual to date
Final
3211
Recruitment outside Australia
Country [1] 20787 0
Ghana
State/province [1] 20787 0
Kumasi
Country [2] 20788 0
India
State/province [2] 20788 0
New Delhi
Country [3] 20789 0
Nigeria
State/province [3] 20789 0
Ile-Ife
Country [4] 20790 0
Malawi
State/province [4] 20790 0
Blantyre
Country [5] 20791 0
Tanzania, United Republic Of
State/province [5] 20791 0
Dar es Salaam

Funding & Sponsors
Funding source category [1] 300444 0
Charities/Societies/Foundations
Name [1] 300444 0
Bill and Melinda Gates Foundation
Country [1] 300444 0
United States of America
Primary sponsor type
Other
Name
World Health Organization
Address
Avenue Appia 20 , CH 1211, Geneva 27, Switzerland
Country
Switzerland
Secondary sponsor category [1] 299905 0
None
Name [1] 299905 0
Address [1] 299905 0
Country [1] 299905 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301244 0
WHO Ethical Review Committee
Ethics committee address [1] 301244 0
Ethics committee country [1] 301244 0
Switzerland
Date submitted for ethics approval [1] 301244 0
13/04/2017
Approval date [1] 301244 0
06/10/2017
Ethics approval number [1] 301244 0
ERC0002901

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 2990 2990 0 0
/AnzctrAttachments/375825-1_Information_sheet_at_ANC_04Oct2017.docx (Participant information/consent)
Attachments [2] 2991 2991 0 0
/AnzctrAttachments/375825-2.1_CONSENT_FORM_04Oct2017_revised.doc (Participant information/consent)
Attachments [3] 2992 2992 0 0
/AnzctrAttachments/375825-2.2_VERBAL_CONFIRMATION_OF_CONSENT_AFTER_BIRTH_04Oct2017_revised.doc (Participant information/consent)
Attachments [4] 2993 2993 0 0
/AnzctrAttachments/375825-2.3_CONSENT_FORM_AFTER_BIRTH_04Oct2017_revised.doc (Participant information/consent)
Attachments [5] 2994 2994 0 0
/AnzctrAttachments/375825-2.4_CONFIRMATION_OF_CONSENT_24 HOURS AFTER BIRTH_04Oct2017_revised.doc (Participant information/consent)
Attachments [6] 3042 3042 0 0
/AnzctrAttachments/375825-Approval_protocol_version_3.0_6_Oct_2018.pdf (Ethics approval)
Attachments [7] 3114 3114 0 0
/AnzctrAttachments/375825(v26-09-2018-21-50-14)-Amendment 4 (Nigeria, Ghana, Tanzania, India Malawi)_iKMC STUDY PROTOCOL Version 3.4pdf.pdf (Protocol)

Contacts
Principal investigator
Name 86358 0
Dr Rajiv Bahl (WHO Study Coordinator)
Address 86358 0
Department of Maternal, Newborn, Child and Adolescent Health
World Health Orgnaization
Avenue Appia 20, CH 1211, Geneva 27
Switzerland
Country 86358 0
Switzerland
Phone 86358 0
+41227913766
Fax 86358 0
Email 86358 0
[email protected]
Contact person for public queries
Name 86359 0
Sachiyo Yoshida
Address 86359 0
Technical officer,
Department of Maternal, Newborn, Child and Adolescent Health
World Health Orgnaization
Avenue Appia 20, CH 1211, Geneva 27
Switzerland
Country 86359 0
Switzerland
Phone 86359 0
+41227911054
Fax 86359 0
Email 86359 0
[email protected]
Contact person for scientific queries
Name 86360 0
Suman Rao
Address 86360 0
Prof & Head
Dept. of Neonatology
St. John's Medical College Hospital
Sarjapur Road, Koramangala
Bangalore 560034
Country 86360 0
India
Phone 86360 0
+91 9019569652
Fax 86360 0
Email 86360 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Following information will be collected.
• Baseline characteristics including maternal and family characteristics
• Mother’s risk factors for giving birth to a small baby
• Information about birth, mother’s severe illness at the time of birth, baby’s clinical condition at birth and after birth
• Medical care provided to baby in both intervention and control group in hospital
• Timing and duratio
When will data be available (start and end dates)?
Data collection will end in 2020. Data underlying the published research result may be made available after 12-month from the end of data collection.
Available to whom?
Data will be available on request from WHO at the publication of the results of the study. Since this project is funded by the Bill and Melinda Gates Foundation, published research result will be disseminated through open access policy.
Available for what types of analyses?
Data will be available for various secondary analysis.
How or where can data be obtained?
Data underlying the published research result will be available on request from WHO.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseImpact of continuous Kangaroo Mother Care initiated immediately after birth (iKMC) on survival of newborns with birth weight between 1.0 to < 1.8 kg: Study protocol for a randomized controlled trial.2020https://dx.doi.org/10.1186/s13063-020-4101-1
EmbaseImmediate "kangaroo mother care" and survival of infants with low birth weight.2021https://dx.doi.org/10.1056/NEJMoa2026486
EmbaseEvaluation of the impact of continuous Kangaroo Mother Care (KMC) initiated immediately after birth compared to KMC initiated after stabilization in newborns with birth weight 1.0 to < 1.8 kg on neurodevelopmental outcomes: Protocol for a follow-up study.2023https://dx.doi.org/10.1186/s13063-023-07192-5
N.B. These documents automatically identified may not have been verified by the study sponsor.