Zambia Chlorhexidine Application Trial (ZamCAT)

• ClinicalTrials.gov Identifier: NCT01241318
• Recruitment Status: Completed
• First Posted: November 16, 2010
• Results First Posted: May 3, 2019
• Last Update Posted: August 31, 2020
• Sponsor: Boston University
• Collaborators: Bill and Melinda Gates Foundation; Ministry of Health, Zambia; Zambia Center for Applied Health Research and Development
• Information provided by (Responsible Party): Boston University

Tracking Information

• First Submitted Date: November 12, 2010
• First Posted Date: November 16, 2010
• Results First Submitted Date: December 9, 2016
• Results First Posted Date: May 3, 2019
• Last Update Posted Date: August 31, 2020
• Study Start Date: February 2011
• Actual Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 4, 2019)

• All-cause Neonatal Mortality [ Time Frame: 28 days post-partum ]
  All-cause neonatal mortality based on vital status at 28 days post-partum
• All-cause Neonatal Mortality Among Newborns Who Survived at Least First Day of Life [ Time Frame: 28 days post-partum ]
  All-cause mortality by day 28 of life among newborns who survive at least the first day of life

Original Primary Outcome Measures (submitted: November 12, 2010)

• All-cause neonatal mortality [ Time Frame: 2.5 years ]
  All-cause neonatal mortality based on vital status at 28 days post-partum
• All-cause neonatal mortality among newborns who survived at least first day of life [ Time Frame: 2.5 years ]
  All-cause mortality by day 28 of life among newborns who survive at least the first day of life

Current Secondary Outcome Measures (submitted: February 4, 2019)

• Incidence of Omphalitis [ Time Frame: 28 days postpartum ]
  Omphalitis, or umbilical cord infection, defined as:

  • presence of umbilical cord pus and mild, moderate or severe redness
  • moderate or severe redness without the presence of umbilical cord pus
• Place of Delivery [ Time Frame: 28 days postpartum ]
  The location where mothers gave birth (home versus a health facility) will be compared to their planned delivery location.
• Factors Influencing Delivery Location [ Time Frame: 28 days postpartum ]
  Health facility characteristics and maternal decision making factors that influence choice of delivery location (health facility vs. home delivery)
• Health Facility Characteristics [ Time Frame: 12 months after study initiation ]
  Characterization of the health services available to pregnant women, postpartum women and their offspring as assessed by comprehensive health facility and health worker surveys. This data was assessed and reported on 100 facilities (10 district hospitals and 90 health facilities).

Original Secondary Outcome Measures (submitted: November 12, 2010)

• Incidence of omphalitis [ Time Frame: 2.5 years ]
  Omphalitis, or umbilical cord infection, defined as:

  • presence of umbilical cord pus and mild, moderate or severe redness
  • moderate or severe redness without the presence of umbilical cord pus
• Place of delivery [ Time Frame: 2.5 years ]
  The location where mothers gave birth (home versus a health facility) will be compared to their planned delivery location.
• Factors influencing delivery location [ Time Frame: 2.5 years ]
  Health facility characteristics and maternal decision making factors that influence choice of delivery location (health facility vs. home delivery)
• Health facility characteristics [ Time Frame: 2.5 years ]
  Characterization of the health services available to pregnant women, postpartum women and their offspring as assessed by comprehensive health facility and health worker surveys

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Zambia Chlorhexidine Application Trial
• Official Title: Impact of Chlorhexidine Cord Cleansing for Prevention of Neonatal Mortality in Zambia
• Brief Summary: This will be a cluster-randomized controlled trial to assess whether washing the umbilical cord with a disinfectant (4% chlorhexidine) helps to reduce neonatal deaths in Zambia when compared to the current standard of care, dry cord care.

Detailed Description

The primary goals of the Zambia Chlorhexidine Application Trial (ZamCAT) are to assess whether daily 4% chlorhexidine cord cleansing is more effective than dry cord care for the prevention of neonatal deaths and omphalitis (umbilical cord infection) in Southern Province, Zambia. Secondary goals are to 1) compare where pregnant women plan to deliver and where they actually deliver, and 2) to describe the health services network available to pregnant and postpartum women in case of serious illness among the women and their newborn infants.

Clusters consisting of individual health centers and their respective catchment areas will be assigned to one of two arms. In the intervention clusters, mothers will apply 4% chlorhexidine to their infants daily until 3 days after the cord completely separates. Mothers in the control clusters will use dry cord care as per normal routine standard of care and in accordance with Zambia Ministry of Health policy.

In order to achieve the 4th Millennium Development Goal of reducing child mortality by two-thirds, simple, inexpensive, and scalable interventions are required. If the use of a 4% chlorhexidine umbilical cord wash effectively reduces neonatal mortality, this will be a low-cost intervention that can be easily translated from a research project into a program for countrywide implementation in Zambia. These results will also add to the limited evidence base about the effectiveness of interventions for reduction of neonatal mortality in sub-Saharan Africa.

• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Prevention
• Condition: Sepsis

Intervention

• Drug: Chlorhexidine gluconate (4%)
  Chlorhexidine is a topical antiseptic that has long been tested for safety and widely used in developed country hospitals, pre-surgical antiseptic technique, wound cleaning and disinfection. Mothers will be instructed to apply 10 ml of 4% chlorhexidine once a day following the infants bath every day from birth until three days after the cord completely separates from the infant's body.
  Other Name: topical antiseptic
• Procedure: Dry cord care
  Mothers will be instructed to keep their infants' umbilical cord stumps clean and dry and to not apply any foreign substances to the cord stump.

Study Arms

• Experimental: Chlorhexidine cord care
  Mothers located in health facility catchment areas assigned to this arm will apply Chlorhexidine gluconate (4%) to their infants daily until three days after the cord completely separates. Bottles of chlorhexidine is provided to women during antenatal care.
  Intervention: Drug: Chlorhexidine gluconate (4%)
• Active Comparator: Dry cord care
  Mothers in health facility catchment areas assigned to this arm will use dry cord care - keeping their babies' umbilical stumps clean and dry - as per normal routine standard of care and in accordance with Zambia Ministry of Health policy.
  Intervention: Procedure: Dry cord care

Publications *

• Mullany LC, El Arifeen S, Winch PJ, Shah R, Mannan I, Rahman SM, Rahman MR, Darmstadt GL, Ahmed S, Santosham M, Black RE, Baqui AH. Impact of 4.0% chlorhexidine cleansing of the umbilical cord on mortality and omphalitis among newborns of Sylhet, Bangladesh: design of a community-based cluster randomized trial. BMC Pediatr. 2009 Oct 21;9:67. doi: 10.1186/1471-2431-9-67.
• Mullany LC, Darmstadt GL, Khatry SK, Katz J, LeClerq SC, Shrestha S, Adhikari R, Tielsch JM. Topical applications of chlorhexidine to the umbilical cord for prevention of omphalitis and neonatal mortality in southern Nepal: a community-based, cluster-randomised trial. Lancet. 2006 Mar 18;367(9514):910-8. doi: 10.1016/S0140-6736(06)68381-5.
• Arifeen SE, Mullany LC, Shah R, Mannan I, Rahman SM, Talukder MR, Begum N, Al-Kabir A, Darmstadt GL, Santosham M, Black RE, Baqui AH. The effect of cord cleansing with chlorhexidine on neonatal mortality in rural Bangladesh: a community-based, cluster-randomised trial. Lancet. 2012 Mar 17;379(9820):1022-8. doi: 10.1016/S0140-6736(11)61848-5. Epub 2012 Feb 8.
• Soofi S, Cousens S, Imdad A, Bhutto N, Ali N, Bhutta ZA. Topical application of chlorhexidine to neonatal umbilical cords for prevention of omphalitis and neonatal mortality in a rural district of Pakistan: a community-based, cluster-randomised trial. Lancet. 2012 Mar 17;379(9820):1029-36. doi: 10.1016/S0140-6736(11)61877-1. Epub 2012 Feb 8.
• Solomon H, Henry EG, Herlihy J, Yeboah-Antwi K, Biemba G, Musokotwane K, Bhutta A, Hamer DH, Semrau KEA. Intended versus actual delivery location and factors associated with change in delivery location among pregnant women in Southern Province, Zambia: a prespecified secondary observational analysis of the ZamCAT. BMJ Open. 2022 Mar 7;12(3):e055288. doi: 10.1136/bmjopen-2021-055288.
• Park JH, Hamer DH, Mbewe R, Scott NA, Herlihy JM, Yeboah-Antwi K, Semrau KEA. Components of clean delivery kits and newborn mortality in the Zambia Chlorhexidine Application Trial (ZamCAT): An observational study. PLoS Med. 2021 May 5;18(5):e1003610. doi: 10.1371/journal.pmed.1003610. eCollection 2021 May.
• Henry EG, Semrau K, Hamer DH, Vian T, Nambao M, Mataka K, Scott NA. The influence of quality maternity waiting homes on utilization of facilities for delivery in rural Zambia. Reprod Health. 2017 May 30;14(1):68. doi: 10.1186/s12978-017-0328-z.
• Semrau KEA, Herlihy J, Grogan C, Musokotwane K, Yeboah-Antwi K, Mbewe R, Banda B, Mpamba C, Hamomba F, Pilingana P, Zulu A, Chanda-Kapata P, Biemba G, Thea DM, MacLeod WB, Simon JL, Hamer DH. Effectiveness of 4% chlorhexidine umbilical cord care on neonatal mortality in Southern Province, Zambia (ZamCAT): a cluster-randomised controlled trial. Lancet Glob Health. 2016 Nov;4(11):e827-e836. doi: 10.1016/S2214-109X(16)30215-7. Epub 2016 Sep 29.
• Hamer DH, Herlihy JM, Musokotwane K, Banda B, Mpamba C, Mwangelwa B, Pilingana P, Thea DM, Simon JL, Yeboah-Antwi K, Grogan C, Semrau KE. Engagement of the community, traditional leaders, and public health system in the design and implementation of a large community-based, cluster-randomized trial of umbilical cord care in Zambia. Am J Trop Med Hyg. 2015 Mar;92(3):666-72. doi: 10.4269/ajtmh.14-0218. Epub 2015 Feb 2.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 28, 2015): 77535
• Original Estimated Enrollment (submitted: November 12, 2010): 66300
• Actual Study Completion Date: September 2013
• Actual Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Pregnant women in the 2nd or 3rd trimester
• Age 15 years and above
• Pregnant women who plan to stay in the study area (catchment area of the health facility) for delivery and one month post partum
• Willingness to provide cord care as per the protocol of their cluster
• Willingness to provide informed consent

Exclusion Criteria:

• Pregnant women who are not willing to provide cord care as per the protocol of their cluster
• Pregnant women who are not willing to provide informed consent
• Pregnant women in the 1st trimester
• Pregnant women under age 15 years

Sex/Gender

• Sexes Eligible for Study: All
• Gender Based Eligibility: Yes
• Gender Eligibility Description: pregnant women so only women 15 and older

• Ages: 15 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Zambia

Administrative Information

• NCT Number: NCT01241318
• Other Study ID Numbers: H-29647
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Boston University
• Original Responsible Party: Dr Davidson Hamer, Professor of International Health & Medicine, Boston University Center for Global Health and Development
• Current Study Sponsor: Boston University
• Original Study Sponsor: Same as current

Collaborators

• Bill and Melinda Gates Foundation
• Ministry of Health, Zambia
• Zambia Center for Applied Health Research and Development

Investigators

• Principal Investigator: Davidson H Hamer, MD; Boston University Center for Global Health and Development
• Principal Investigator: Katherine Semrau, PhD; Boston University Center for Global Health and Development

• PRS Account: Boston University
• Verification Date: July 2020