Single-dose Postpartum Vitamin A Supplementation of Mothers and Neonates (ZVITAMBO)
|First Received Date ICMJE||September 12, 2005|
|Last Updated Date||April 9, 2013|
|Start Date ICMJE||November 1997|
|Primary Completion Date||May 2001 (final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
|Original Primary Outcome Measures ICMJE
|Change History||Complete list of historical versions of study NCT00198718 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Single-dose Postpartum Vitamin A Supplementation of Mothers and Neonates|
|Official Title ICMJE||Vitamin A Supplementation of Breast Feeding Mothers and Their Neonates at Delivery: Impact on Mother to Child Transmission of HIV During Lactation, HIV Infection Among Women During the Postpartum Year, and Infant Mortality.|
The ZVITAMBO PROJECT is testing whether giving mothers and infants a single large dose of vitamin A during the immediate post partum period will reduce:
Random subsamples of maternal and infant blood were evaluated for anemia and iron status to determine the effect of vitamin A on hematopoiesis and serum and breast milk retinol (mothers) and modified relative dose response test (infants) to determine the effect of vitamin A on vitamin A status.
A subsample of maternal and infant blood samples were evaluated for the presence of HLA-E, HLA-G, and TAP polymorphisms and their relation to prevalent HIV infection in mothers and risk of mother to child transmission.
The Zimbabwe Vitamin A for Mothers and Babies (ZVITAMBO) project was a placebo-controlled randomized trial, which enrolled 14,110 mothers and their infants within 96 hours of delivery from one of 14 hospitals and clinics in greater Harare between November 25, 1997 and January 29, 2000. Mother-baby pairs were eligible if neither had an acutely life threatening condition, the baby was a singleton with birth weight >1500 g, and the mother planned to stay in Harare after delivery. Written informed consent was obtained from the mother. Socio-economic and demographic characteristics were collected by interview and obstetric details of the pregnancy and delivery were transcribed from hospital records. Gestational age was estimated. Infant birth weight was measured using an electronic scale. Infant length, infant head circumference, and maternal arm circumference were measured. Arm circumference was measured as an indicator of maternal nutritional status rather than Body Mass Index because it is less influenced by fluid fluctuations during the immediate post partum period. Addresses were recorded for the mother's urban and rural residences (it is common for urban Zimbabweans to travel frequently to extended family rural homesteads), her place of work, her husband's place of work, and that of relative who would always know her whereabouts.
At recruitment, study nurses collected plasma and serum from mothers and babies. Maternal plasma was stored at room temperature (~20° C) and other samples in a cool box (~ 10-15° C) before being transferred to the laboratory within 2 hr of collection.
Mother-baby pairs were randomized to one of four treatment groups: mother received 400,000 IU vitamin A (as retinyl palmitate) and baby received 50,000 IU vitamin A (Aa group); mother received 400,000 IU vitamin A and baby received placebo (Ap group); mother received placebo and baby received 50,000 IU vitamin A (Pa group); and both mother and baby received placebo (Pp group). Treatment and placebo capsules appeared identical and both contained a soy oil base with vitamin E as a preservative (50 IU per maternal capsule; 10 IU per infant capsule) (Tishcon Corporation, Westbury, NY, USA).
A separate team at Johns Hopkins University prepared the study capsule packets. Study identification numbers were randomly allocated to the treatment groups by computer in blocks of 12. The numbers were printed on adhesive labels and affixed to amber-colored zip-lock plastic bags that were packed with the assigned capsules. Capsule packets were prepared separately for each of the four treatment groups, and then merged into numeric order before shipping to Zimbabwe where series of packets were distributed to each recruitment site. As each mother-baby pair was recruited, the capsules in the next sequential bag were administered, and the associated study number assigned to the pair. Lists linking the study number to the treatment were kept in sealed envelopes and encrypted computer files that were not accessible to the Zimbabwe-based study team.
Pairs were followed at 6 wk, 3 mo, and then 3 monthly up to 24 months at one of three study clinics. Home visits were attempted for defaulting pairs to either their urban or rural home anywhere within the Zimbabwe borders. We initially planned to follow all HIV-positive mothers and their infants and a ~50% random sample of HIV-negative mothers and their infants for 24 months. However, in June 2000, economic conditions necessitated discontinuing the second year of follow up. This meant that 24%, 48% and 100% of the pairs were reassigned to 24 months, >18 month, and >12 month follow up, respectively. Follow up visits included assessment of recent illness, sick clinic visits, and hospitalizations by the mother or infant; anthropometric measures, infant dietary history, maternal sexual and reproductive health practices, and blood and breast milk sampling. Free clinical care included treatment of acute infections with appropriate antimicrobial drugs, referral to government treatment facilities for suspect tuberculosis, counseling and antibiotic treatment for mastitis, and oral rehydration solution education for diarrhea. HIV-related and psychosocial counseling was available throughout the study.
For mothers and infants who died, cause of death was determined from medical records for infants who died in a hospital or from review of verbal autopsy information by a study pediatrician (infants) or study obstetrician (mothers), who were masked to treatment group, for infants dying at home. Multiple causes of death were permitted and were not ranked hierarchically, in keeping with the recommendations of an expert group convened by the World Health Organization.
Maternal plasma were tested for HIV at baseline by two ELISA tests run in parallel, and by Western Blot when duplicate pairs of ELISA test results were discordant. Mothers who tested negative at baseline were retested for HIV at every blood sampling. Quality control was monitored by use of kits controls, inclusion of an internal QC sample on every plate, and participation in the quality assurance program for HIV testing of the Zimbabwe Ministry of Health. Serum retinol concentration was measured in a subsample of mothers and babies by HPLC; quality control was monitored by inclusion of standards provided by the National Institute of Standards and Technology (Gaithersburg, MD, USA) and participation in their quality assurance program Hemoglobin was measured for women enrolled from October 1, 1998 to the end of the study (about 60% of the total sample) by HemoCue (Mission Viejo, CA). Among mothers who were HIV-positive at recruitment, CD4 cells were enumerated within 48 hours of phlebotomy (Facscount, Becton Dickinson International, Erembodegem, Belgium), and viral load was measured in a subsample (Roche Amplicor HIV-1 Monitor test version 1.5, Roche Diagnostics, Alameda, CA, USA).
Plasma and cell pellets were archived from HIV-exposed infants at all visits. After follow-up was completed, the last available specimen from each infant was tested (plasma by GeneScreen ELISA for samples collected ≥18 months; or cell pellets by Amplicor HIV -1 DNA test version 1.5 (Roche Diagnostic Systems) for samples collected <18 months). If this sample was HIV-negative, the infant was classified as negative; if it was HIV-positive, samples collected at younger ages were tested to determine timing of infection.
Education and counseling about infant feeding in the context of HIV was updated throughout the trial. When the trial began, information about HIV transmission through breastfeeding was scanty. In June 1998, new infant feeding guidelines were published by UNAIDS/UNICEF/WHO stating that HIV-positive mothers should be fully informed about the risks and benefits of infant feeding alternatives and empowered to make their best personal choice. In response, we modified our procedures to provide 24-hour turn-around time for maternal HIV test results. Study nurses were trained to counsel HIV-positive women about feeding options and kitchens were established for teaching safe replacement feeding. Additional funding was obtained to conduct formative research to inform a more effective program to educate mothers about infant feeding in the context of HIV. This program included group education, incorporating infant feeding issues into individual counseling, and integrating mother to child HIV transmission issues into on-going work-site education programs targeting men, which were being run by other organizations in Harare. The program was fully implemented within the trial by November 1st 1999. It emphasized exclusive breastfeeding for HIV-positive mothers who chose to breastfeed, optimal breastfeeding techniques to avoid cracked nipples, milk stasis, and mastitis; prompt treatment of breast problems; and safe sex practices especially during the breastfeeding period. These four 'safer breastfeeding' practices were also promoted among all status-unknown and HIV negative women. Known HIV-positive women were counseled to stop breastfeeding early.
All laboratory analyses and data management was conducted in Harare. The protocol and interim analyses were reviewed by an external data safety and monitoring committee.
The study protocol was approved by the Medical Research Council of Zimbabwe, The Medicines Control Authority of Zimbabwe, The Johns Hopkins Bloomberg School of Public Health Committee on Human Research, and the Montreal General Hospital Ethics Committee.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 2|
|Study Design ICMJE||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Intervention ICMJE||Drug: Vitamin A (retinyl palmitate)|
|Study Arm (s)||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Active, not recruiting|
|Estimated Completion Date||May 2015|
|Primary Completion Date||May 2001 (final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
|Ages||18 Years and older|
|Accepts Healthy Volunteers||Yes|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Location Countries ICMJE||Not Provided|
|NCT Number ICMJE||NCT00198718|
|Other Study ID Numbers ICMJE||(CIDA) (R/C Project 690/M3688)|
|Has Data Monitoring Committee||Not Provided|
|Responsible Party||Jean Humphrey, Johns Hopkins Bloomberg School of Public Health|
|Study Sponsor ICMJE||Johns Hopkins Bloomberg School of Public Health|
|Information Provided By||Johns Hopkins Bloomberg School of Public Health|
|Verification Date||April 2013|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP