Sepsis
Conditions
Keywords
neonate, omphalitis, neonatal mortality, maternal health, umbilical cord infection
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.
Interventions
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.
PROCEDUREDry 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.
Sponsors
Bill and Melinda Gates Foundation
Ministry of Health, Zambia
Zambia Center for Applied Health Research and Development
Boston University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
15 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| All-cause Neonatal Mortality | 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 | 28 days post-partum | All-cause mortality by day 28 of life among newborns who survive at least the first day of life |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Omphalitis | 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 | 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 | 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 | 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). |
Countries
Zambia
Participant flow
Recruitment details
In the 90 clusters (i.e. government-run health facilities), pregnant women who met eligibility criteria attending antenatal care were offered enrollment. Recruitment started February 15, 2011 and ended January 30, 2013.
Pre-assignment details
Mothers were enrolled in the study while pregnant and infants were enrolled after delivery; thus the total protocol enrollment is women + infants. Study reporting is completed at the woman level and thus the total enrolled is listed at the woman level in the outcomes tables.
Participants by arm
| Arm | Count |
|---|---|
| Chlorhexidine Cord Care Mothers located in health facility catchment areas assigned to this arm will apply chlorhexidine to their infants daily until three days after the cord completely separates.
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. | 19,629 |
| 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.
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. | 20,050 |
| Total | 39,679 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 2 | 4 |
| Overall Study | Lost to Follow-up | 740 | 455 |
| Overall Study | Withdrawal by Subject | 175 | 46 |
| Overall Study | Withdrew/Lost to Follow after delivery | 60 | 38 |
| Overall Study | Woman: false pregnancies | 27 | 15 |
| Overall Study | Woman: miscarriage/abortion | 46 | 38 |
| Overall Study | Woman: Stillborn infant | 129 | 146 |
Baseline characteristics
| Characteristic | Chlorhexidine Cord Care | Dry Cord Care | Total |
|---|---|---|---|
| Age, Customized 20-35 years | 12772 participants | 13122 participants | 25894 participants |
| Age, Customized <20 years | 4671 participants | 4580 participants | 9251 participants |
| Age, Customized >35 years | 2012 participants | 2194 participants | 4206 participants |
| Age, Customized Missing (not recorded) | 174 participants | 154 participants | 328 participants |
| Gestational Age at enrollment | 28.0 weeks STANDARD_DEVIATION 7.2 | 28.4 weeks STANDARD_DEVIATION 7.2 | 28.3 weeks STANDARD_DEVIATION 7.2 |
| Gravida | 3.5 deliveries STANDARD_DEVIATION 2.3 | 3.6 deliveries STANDARD_DEVIATION 2.4 | 3.6 deliveries STANDARD_DEVIATION 2.4 |
| Household water source Community tap | 1919 participants | 1761 participants | 3680 participants |
| Household water source Community well or river | 13241 participants | 13768 participants | 27009 participants |
| Household water source Household tap | 1861 participants | 1715 participants | 3576 participants |
| Household water source Missing (Not recorded) | 190 participants | 175 participants | 365 participants |
| Household water source No answer from Mother | 56 participants | 62 participants | 118 participants |
| Household water source Other | 67 participants | 166 participants | 233 participants |
| Household water source Other water source on own property | 2295 participants | 2403 participants | 4698 participants |
| Marital Status Cohabiting | 109 participants | 89 participants | 198 participants |
| Marital Status Married | 16107 participants | 16499 participants | 32606 participants |
| Marital Status Missing (not recorded) | 168 participants | 142 participants | 310 participants |
| Marital Status Separated, divorced or widowed | 224 participants | 187 participants | 411 participants |
| Marital Status Single | 3021 participants | 3133 participants | 6154 participants |
| Maternal Education Do not know | 3 participants | 10 participants | 13 participants |
| Maternal Education Junior Secondary | 5422 participants | 5499 participants | 10921 participants |
| Maternal Education Lower Primary | 2293 participants | 2563 participants | 4856 participants |
| Maternal Education Missing (not recorded) | 169 participants | 146 participants | 315 participants |
| Maternal Education No eduction | 1936 participants | 1958 participants | 3894 participants |
| Maternal Education Upper Primary | 7731 participants | 7874 participants | 15605 participants |
| Maternal Education >Upper Secondary | 180 participants | 160 participants | 340 participants |
| Maternal Education Upper Secondary | 1895 participants | 1840 participants | 3735 participants |
| Maternal literacy A bit | 8835 participants | 9516 participants | 18351 participants |
| Maternal literacy Missing (not recorded) | 188 participants | 147 participants | 335 participants |
| Maternal literacy No response from mother | 77 participants | 61 participants | 138 participants |
| Maternal literacy Not at all | 5037 participants | 5491 participants | 10528 participants |
| Maternal literacy Very well | 5492 participants | 4835 participants | 10327 participants |
| Parity | 2.4 pregnancies STANDARD_DEVIATION 2.3 | 2.5 pregnancies STANDARD_DEVIATION 2.4 | 2.5 pregnancies STANDARD_DEVIATION 2.4 |
| Race/Ethnicity, Customized Bemba | 413 participants | 433 participants | 846 participants |
| Race/Ethnicity, Customized Ila | 105 participants | 121 participants | 226 participants |
| Race/Ethnicity, Customized Lozi | 786 participants | 795 participants | 1581 participants |
| Race/Ethnicity, Customized Missing (not recorded) | 168 participants | 138 participants | 306 participants |
| Race/Ethnicity, Customized Nyanja | 525 participants | 432 participants | 957 participants |
| Race/Ethnicity, Customized Other | 629 participants | 481 participants | 1110 participants |
| Race/Ethnicity, Customized Tonga | 17003 participants | 17650 participants | 34653 participants |
| Region of Enrollment Zambia | 19629 participants | 20050 participants | 39679 participants |
| Sex: Female, Male Female | 19629 Participants | 20050 Participants | 39679 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Slept under mosquito bednet the previous night Missing (not recorded) | 227 participants | 192 participants | 419 participants |
| Slept under mosquito bednet the previous night No | 8310 participants | 8075 participants | 16385 participants |
| Slept under mosquito bednet the previous night Yes | 11092 participants | 11783 participants | 22875 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 282 / 18,510 | 263 / 19,346 |
| other Total, other adverse events | 9 / 18,510 | 0 / 19,346 |
| serious Total, serious adverse events | 0 / 18,510 | 0 / 19,346 |
Outcome results
Primary
All-cause Neonatal Mortality
All-cause neonatal mortality based on vital status at 28 days post-partum
Time frame: 28 days post-partum
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Chlorhexidine Cord Care | All-cause Neonatal Mortality | Neonatal mortality | 282 participants |
| Chlorhexidine Cord Care | All-cause Neonatal Mortality | Survived to day 28 | 18168 participants |
| Dry Cord Care | All-cause Neonatal Mortality | Survived to day 28 | 19045 participants |
| Dry Cord Care | All-cause Neonatal Mortality | Neonatal mortality | 263 participants |
95% CI: [0.88, 1.44]
Primary
All-cause Neonatal Mortality Among Newborns Who Survived at Least First Day of Life
All-cause mortality by day 28 of life among newborns who survive at least the first day of life
Time frame: 28 days post-partum
Population: All liveborn neonates who survived the first 24 hours after delivery
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Chlorhexidine Cord Care | All-cause Neonatal Mortality Among Newborns Who Survived at Least First Day of Life | Neonatal mortality | 200 neonates who survived first 24 hours |
| Chlorhexidine Cord Care | All-cause Neonatal Mortality Among Newborns Who Survived at Least First Day of Life | Survived to day 28 | 18224 neonates who survived first 24 hours |
| Dry Cord Care | All-cause Neonatal Mortality Among Newborns Who Survived at Least First Day of Life | Neonatal mortality | 186 neonates who survived first 24 hours |
| Dry Cord Care | All-cause Neonatal Mortality Among Newborns Who Survived at Least First Day of Life | Survived to day 28 | 19080 neonates who survived first 24 hours |
95% CI: [0.86, 1.47]
Secondary
Factors Influencing Delivery Location
Health facility characteristics and maternal decision making factors that influence choice of delivery location (health facility vs. home delivery)
Time frame: 28 days postpartum
Population: Women enrolled in the ZamCAT study and delivery location known. Please note these are different denominators reported as this analysis is not based on intervention randomization, but rather an analysis focused on women's location of childbirth. Therefore, the number of women included in this analysis is based on a subset of all women enrolled.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Chlorhexidine Cord Care | Factors Influencing Delivery Location | Family/Social Expectations | 1255 Participants |
| Chlorhexidine Cord Care | Factors Influencing Delivery Location | Same Location as Prior Delivery | 3198 Participants |
| Chlorhexidine Cord Care | Factors Influencing Delivery Location | Need for Skilled Attendance12991 | 12991 Participants |
| Chlorhexidine Cord Care | Factors Influencing Delivery Location | Financial Constraints | 1823 Participants |
| Chlorhexidine Cord Care | Factors Influencing Delivery Location | Physical Distance | 6345 Participants |
| Chlorhexidine Cord Care | Factors Influencing Delivery Location | Relationship with Provider | 572 Participants |
| Chlorhexidine Cord Care | Factors Influencing Delivery Location | Safety for Mother/Baby | 14129 Participants |
| Chlorhexidine Cord Care | Factors Influencing Delivery Location | Other | 1480 Participants |
| Chlorhexidine Cord Care | Factors Influencing Delivery Location | Missing | 1364 Participants |
| Dry Cord Care | Factors Influencing Delivery Location | Missing | 770 Participants |
| Dry Cord Care | Factors Influencing Delivery Location | Relationship with Provider | 429 Participants |
| Dry Cord Care | Factors Influencing Delivery Location | Same Location as Prior Delivery | 2082 Participants |
| Dry Cord Care | Factors Influencing Delivery Location | Family/Social Expectations | 990 Participants |
| Dry Cord Care | Factors Influencing Delivery Location | Need for Skilled Attendance12991 | 5693 Participants |
| Dry Cord Care | Factors Influencing Delivery Location | Other | 803 Participants |
| Dry Cord Care | Factors Influencing Delivery Location | Financial Constraints | 1249 Participants |
| Dry Cord Care | Factors Influencing Delivery Location | Safety for Mother/Baby | 5911 Participants |
| Dry Cord Care | Factors Influencing Delivery Location | Physical Distance | 3930 Participants |
Secondary
Health Facility Characteristics
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).
Time frame: 12 months after study initiation
Population: Health facilities
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Chlorhexidine Cord Care | Health Facility Characteristics | Basic emergency obstetrical and newborn care | 6 Health facilities |
| Chlorhexidine Cord Care | Health Facility Characteristics | No basic emergency obstetrical and newborn care | 94 Health facilities |
Secondary
Incidence of Omphalitis
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
Time frame: 28 days postpartum
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Chlorhexidine Cord Care | Incidence of Omphalitis | Omphalitis | 82 neonates |
| Chlorhexidine Cord Care | Incidence of Omphalitis | No omphalitis | 18428 neonates |
| Dry Cord Care | Incidence of Omphalitis | Omphalitis | 118 neonates |
| Dry Cord Care | Incidence of Omphalitis | No omphalitis | 19228 neonates |
95% CI: [0.47, 1.13]
Secondary
Place of Delivery
The location where mothers gave birth (home versus a health facility) will be compared to their planned delivery location.
Time frame: 28 days postpartum
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Chlorhexidine Cord Care | Place of Delivery | Home Delivery | 6509 Participants |
| Chlorhexidine Cord Care | Place of Delivery | Facility Delivery | 11456 Participants |
| Chlorhexidine Cord Care | Place of Delivery | Other | 190 Participants |
| Chlorhexidine Cord Care | Place of Delivery | Missing | 355 Participants |
| Dry Cord Care | Place of Delivery | Missing | 332 Participants |
| Dry Cord Care | Place of Delivery | Home Delivery | 6682 Participants |
| Dry Cord Care | Place of Delivery | Other | 128 Participants |
| Dry Cord Care | Place of Delivery | Facility Delivery | 12204 Participants |