Impact of Chlorhexidine Cleansing on Bacteria Colonizing the Umbilical Cord of Infants in Bangladesh

• Sponsor: Johns Hopkins Bloomberg School of Public Health (Other)
• Overall Status: Completed
• CT.gov ID: NCT00719329
• Collaborator: Dhaka Shishu Hospital (Other), Shimantik, Bangladesh (Other), Thrasher Research Fund (Other)
• Enrollment: 1,931
• Locations: 3
• Arms: 3
• Duration (Months): 13
• Patients Per Site: 643.7
• Patients Per Site Per Month: 49.5

Study Details

Study Description

Brief Summary

Background: In developing countries, many babies are born at home and the umbilical cord commonly becomes infected during the first week after birth, and can be deadly. Cleansing of the cord with a low-cost antiseptic like chlorhexidine may reduce the risk of these infections. Little is known, however, about the frequency of chlorhexidine cleansing needed to impact upon the overall presence of bacteria on the stump, or regarding the changes in bacteria during the first week of life when most cord infections occur.

Objectives: We will describe the profile of bacteria colonizing the umbilical cord stump of infants in rural Bangladesh and examine the role of topical chlorhexidine in altering colonization and progress of infection. We will compare the overall and bacteria-specific rate of colonization of the cord stump between infants receiving chlorhexidine cleansing of their cord through the first day or first week of life. We will also quantify the relationship between colonization of the cord stump with specific pathogens and the presence and severity of signs of umbilical cord infection (pus, redness, swelling) among these newborns.

Potential Impact: More information is needed on the impact of single versus repeated applications of chlorhexidine to the cord stump, as the number of cleansing may substantially influence the feasibility of widespread scale-up in many populations. The data generated from this proposed study will guide the most appropriate design of this simple intervention and will help inform specific treatment protocols for effective management of infants with signs of umbilical cord infections.

Condition or Disease	Intervention/Treatment	Phase
Infection	Drug: Chlorhexidine 4.0%; Behavioral: Dry Cord Care	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 1931 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Bacterial Colonization of the Neonatal Umbilical Cord and Impact of 4.0% Chlorhexidine Cleansing on the Bacteriological Profile of the Umbilical Cord of Newborns in Sylhet District, Bangladesh
• Study Start Date: Aug 1, 2008
• Actual Primary Completion Date: Sep 1, 2009
• Actual Study Completion Date: Sep 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A Chlorhexidine cleansing of the cord for seven days	Drug: Chlorhexidine 4.0%; Solution (4.0%, 7.1% CHX-D)
Experimental: B Chlorhexidine cleansing of the cord for 1 day	Drug: Chlorhexidine 4.0%; Solution (4.0%, 7.1% CHX-D)
Placebo Comparator: C Dry cord care, as recommended by WHO	Behavioral: Dry Cord Care; Educational messages regarding clean cord care

Outcome Measures

Primary Outcome Measures

1. Colonization at Day 1 Swab [First week of life]

   Was the swab collected on the day 1 visit (usually within 24 hours of birth) positive for any organism? If so, this is defined as positive.

2. Colonization at Day 3 Swab [First Week of Life]

   Were any organisms found on the swab collected on at Day 03

3. Colonization at Day 7 Swab [First Week of Life]

   Were any organisms found on the swab collected on the day 07 visit?

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 7 Days
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Enrolled in parent chlorhexidine cleansing trial

Exclusion Criteria:

• Not enrolled in parent trial

• First visited after 48 hours of life

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Johns Hopkins Bloomberg School of Public Health	Baltimore	Maryland	United States	21205
2	Projahnmo	Sylhet City	Sylhet	Bangladesh
3	Dhaka Shishu Hospital	Dhaka		Bangladesh

Sponsors and Collaborators

• Johns Hopkins Bloomberg School of Public Health
• Dhaka Shishu Hospital
• Shimantik, Bangladesh
• Thrasher Research Fund

Investigators

• Study Director: Luke C Mullany, PhD, Johns Hopkins Bloomberg School of Public Health

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Luke C. Mullany, Associate Professor, Johns Hopkins Bloomberg School of Public Health
• ClinicalTrials.gov Identifier: NCT00719329
• Other Study ID Numbers: THRASHER-02827-0
• First Posted: Jul 21, 2008
• Last Update Posted: Apr 20, 2012
• Last Verified: Mar 1, 2012

• Keywords provided by Luke C. Mullany, Associate Professor, Johns Hopkins Bloomberg School of Public Health: chlorhexidine; umbilical cord
• Additional relevant MeSH terms: Chlorhexidine

Study Results

Participant Flow

Recruitment Details	All babies recruited between September 2008 and September 2009
Pre-assignment Detail	Babies were allocated based on their cluster allocation (i.e. location of birth) in the parent trial

Arm/Group Title	CHX Cleansing - 7 Days	CHX Cleansing - 1 Day	Dry Cord Care
Arm/Group Description	Chlorhexidine cleansing of the cord for seven days	Chlorhexidine cleansing of the cord for 1 day	Dry cord care, as recommended by WHO
Period Title: Overall Study
STARTED	705	571	647
Day 1 Swab	705	569	646
Day 3 Swab	614	501	578
Day 7 Swab	593	467	561
COMPLETED	705	569	646
NOT COMPLETED	0	2	1

Baseline Characteristics

Arm/Group Title	CHX Cleansing - 7 Days	CHX Cleansing - 1 Day	Dry Cord Care	Total
Arm/Group Description	Chlorhexidine cleansing of the cord for seven days	Chlorhexidine cleansing of the cord for 1 day	Dry cord care, as recommended by WHO	Total of all reporting groups
Overall Participants	705	571	647	1923
Age, Customized (Number) [Number]
[0, 6) Hours	464 65.8%	350 61.3%	425 65.7%	1239 64.4%
[6, 12) Hours	114 16.2%	104 18.2%	106 16.4%	324 16.8%
[12, 24) Hours	84 11.9%	72 12.6%	86 13.3%	242 12.6%
>=24 Hours	43 6.1%	45 7.9%	30 4.6%	118 6.1%
Sex: Female, Male (Count of Participants)
Female	339 48.1%	292 51.1%	316 48.8%	947 49.2%
Male	366 51.9%	279 48.9%	331 51.2%	976 50.8%

Outcome Measures

1. Primary Outcome

Title	Colonization at Day 1 Swab
Description	Was the swab collected on the day 1 visit (usually within 24 hours of birth) positive for any organism? If so, this is defined as positive.
Time Frame	First week of life

Outcome Measure Data

Analysis Population Description

Intention to Treat

Arm/Group Title	CHX Cleansing - 7 Days	CHX Cleansing - 1 Day	Dry Cord Care
Arm/Group Description	Babies in this group were born in clusters allocated to 7 days of chlorhexidine cleansing to the cord	Babies in this group were born in clusters allocated to 1 days of chlorhexidine cleansing to the cord	Babies in this group were born in clusters allocated to 0 days of chlorhexidine cleansing to the cord
Measure Participants	705	569	646
Positive - one or more organisms found	466 66.1%	396 69.4%	605 93.5%
Negative - no organisms found	239 33.9%	173 30.3%	41 6.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CHX Cleansing - 1 Day, Dry Cord Care
	Comments	Comparison of colonization prevalence, relative to dry cord care group
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Prevalence Rate Ratio
	Estimated Value	0.75
	Confidence Interval	(2-Sided) 95%; 0.70 to 0.81
	Parameter Dispersion	Type: Value:
	Estimation Comments	Prevalence Rate Ratio - Comparing Single CHX Cleansing to Dry Cord Care

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	CHX Cleansing - 7 Days, Dry Cord Care
	Comments	Comparison of colonization prevalence, relative to dry cord care group
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Prevalence Rate Ratio
	Estimated Value	0.71
	Confidence Interval	(2-Sided) 95%; 0.66 to 0.77
	Parameter Dispersion	Type: Value:
	Estimation Comments	Prevalence Rate Ratio - Comparing Multiple CHX Cleansing to Dry Cord Care

2. Primary Outcome

Title	Colonization at Day 3 Swab
Description	Were any organisms found on the swab collected on at Day 03
Time Frame	First Week of Life

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	CHX Cleansing - 7 Days	CHX Cleansing - 1 Day	Dry Cord Care
Arm/Group Description	Babies in this group were born in clusters allocated to 7 days of chlorhexidine cleansing of the cord	Babies in this group were born in clusters allocated to 1 days of chlorhexidine cleansing of the cord	Babies in this group were born in clusters allocated to 0 days of chlorhexidine cleansing of the cord
Measure Participants	614	501	578
Positive for any organisms	363 51.5%	381 66.7%	563 87%
Negative for any organisms	251 35.6%	120 21%	15 2.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CHX Cleansing - 1 Day, Dry Cord Care
	Comments	Comparison of colonization prevalence, relative to dry cord care group
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Prevalence Rate Ratio
	Estimated Value	0.78
	Confidence Interval	(2-Sided) 95%; 0.74 to 0.82
	Parameter Dispersion	Type: Value:
	Estimation Comments	Prevalence Ratio Ratio - Comparing Single Cleansing to Dry Cord Care

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	CHX Cleansing - 7 Days, Dry Cord Care
	Comments	Comparison of colonization prevalence, relative to dry cord care group
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Prevalence Rate Ratio
	Estimated Value	0.61
	Confidence Interval	(2-Sided) 95%; 0.57 to 0.65
	Parameter Dispersion	Type: Value:
	Estimation Comments	Prevalence Rate Ratio - Comparing Multiple Cleansing to Dry Cord Care

3. Primary Outcome

Title	Colonization at Day 7 Swab
Description	Were any organisms found on the swab collected on the day 07 visit?
Time Frame	First Week of Life

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	CHX Cleansing - 7 Days	CHX Cleansing - 1 Day	Dry Cord Care
Arm/Group Description	Babies in this group were born in clusters allocated to 7 days of chlorhexidine cleansing of the cord	Babies in this group were born in clusters allocated to 1 days of chlorhexidine cleansing of the cord	Babies in this group were born in clusters allocated to 0 days of chlorhexidine cleansing of the cord
Measure Participants	593	467	561
Positive for any organisms	328 46.5%	415 72.7%	540 83.5%
Negative for any organisms	265 37.6%	52 9.1%	21 3.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CHX Cleansing - 1 Day, Dry Cord Care
	Comments	Comparison of colonization prevalence, relative to dry cord care group
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Prevalence Rate Ratio
	Estimated Value	0.92
	Confidence Interval	(2-Sided) 95%; 0.89 to 0.96
	Parameter Dispersion	Type: Value:
	Estimation Comments	Prevalence Rate Ratio - Comparing Single Cleansing to Dry Cord Care

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	CHX Cleansing - 7 Days, Dry Cord Care
	Comments	Comparison of colonization prevalence, relative to dry cord care group
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Prevalence Rate Ratio
	Estimated Value	0.57
	Confidence Interval	(2-Sided) 95%; 0.53 to 0.63
	Parameter Dispersion	Type: Value:
	Estimation Comments	Prevalence Ratio Ratio - Comparing Multiple Cleansing to Dry Cord Care

Adverse Events

Arm/Group Title	CHX Cleansing - 7 Days		CHX Cleansing - 1 Day		Dry Cord Care
Arm/Group Description	Chlorhexidine cleansing of the cord for seven days		Chlorhexidine cleansing of the cord for 1 day		Dry cord care, as recommended by WHO
All Cause Mortality
	CHX Cleansing - 7 Days		CHX Cleansing - 1 Day		Dry Cord Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	CHX Cleansing - 7 Days		CHX Cleansing - 1 Day		Dry Cord Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/705 (0%)		0/571 (0%)		0/647 (0%)
Other (Not Including Serious) Adverse Events
	CHX Cleansing - 7 Days		CHX Cleansing - 1 Day		Dry Cord Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/705 (0%)		0/571 (0%)		0/647 (0%)

Limitations/Caveats

Not all possible swab data were available for each baby due to staff leave/holiday, unplanned work stoppage, child/mother absent/moved/died, swab collected but not processed - these reasons did not differ between the groups

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.