Probiotic Prophylaxis of Hirschprung's Disease Associated Enterocolitis (HAEC)

• ClinicalTrials.gov Identifier: NCT00630838
• Recruitment Status: Completed
• First Posted: March 7, 2008
• Results First Posted: July 19, 2016
• Last Update Posted: July 19, 2016
• Sponsor: University of Michigan
• Information provided by (Responsible Party): Daniel H. Teitelbaum, University of Michigan

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Prevention
• Condition: Hirschsprung Disease
• Interventions: Drug: VSL#3; Drug: Placebo
• Enrollment: 62

Participant Flow

Recruitment Details	All participants scheduled for endorectal pullthrough who were consented were randomized, but 1 died following the surgery prior to any study specific placebo usage.
Pre-assignment Details

Arm/Group Title	VSL#3 Probiotic	Placebo
Arm/Group Description	VSL#3 probiotic VSL#3 : Dosing will be based on patient weight. For those infants greater or equal to 5 kg, one gram (360 billion bacteria or 4 sachets) of VSL#3 will be administered into 3 ounces of either expressed breast milk or formula daily. For patients under 5 kg, 0.5 gm (180 billion bacteria or 2 sachets) daily in the same amount of formula or breast milk. E.2.6. Time of start of probiotics: Probiotic vs. placebo will begin once the infant has reached full oral feeding.	Dosing will be based on patient weight. For those infants greater or equal to 5 kg, one gram (4 sachets) of placebo will be administered into 3 ounces of either expressed breast milk or formula daily. For patients under 5 kg, 0.5 gm (2 sachets) daily in the same amount of formula or breast milk Initiation: within one week of pullthrough Duration: 3 months Placebo : Dosing will be based on patient weight. For those infants greater or equal to 5 kg, one gram (4 sachets) of placebo will be administered into 3 ounces of either expressed breast milk or formula daily. For patients under 5 kg, 0.5 gm (2 sachets) daily in the same amount of formula or breast milk Initiation: within one week of pullthrough Duration: 3 months
Period Title: Overall Study
Started	32	30
Completed	32	28
Not Completed	0	2
Reason Not Completed
Death	0	1
Lost to Follow-up	0	1

Baseline Characteristics

Arm/Group Title		VSL#3 Probiotic	Placebo	Total
Arm/Group Description		VSL#3 probiotic VSL#3 : Dosing will be based on patient weight. For those infants greater or equal to 5 kg, one gram (360 billion bacteria or 4 sachets) of VSL#3 will be administered into 3 ounces of either expressed breast milk or formula daily. For patients under 5 kg, 0.5 gm (180 billion bacteria or 2 sachets) daily in the same amount of formula or breast milk. E.2.6. Time of start of probiotics: Probiotic vs. placebo will begin once the infant has reached full oral feeding.	Dosing will be based on patient weight. For those infants greater or equal to 5 kg, one gram (4 sachets) of placebo will be administered into 3 ounces of either expressed breast milk or formula daily. For patients under 5 kg, 0.5 gm (2 sachets) daily in the same amount of formula or breast milk Initiation: within one week of pullthrough Duration: 3 months Placebo : Dosing will be based on patient weight. For those infants greater or equal to 5 kg, one gram (4 sachets) of placebo will be administered into 3 ounces of either expressed breast milk or formula daily. For patients under 5 kg, 0.5 gm (2 sachets) daily in the same amount of formula or breast milk Initiation: within one week of pullthrough Duration: 3 months	Total of all reporting groups
Overall Number of Baseline Participants		32	30	62
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	32 participants	30 participants	62 participants
	<=18 years	32 100.0%	30 100.0%	62 100.0%
	Between 18 and 65 years	0 0.0%	0 0.0%	0 0.0%
	>=65 years	0 0.0%	0 0.0%	0 0.0%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Months
	Number Analyzed	32 participants	30 participants	62 participants
		32 (7.6)	28 (4.9)	30 (5.6)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	32 participants	30 participants	62 participants
	Female	14 43.8%	5 16.7%	19 30.6%
	Male	18 56.3%	25 83.3%	43 69.4%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants	Number Analyzed	32 participants	30 participants	62 participants
United States		10	10	20
Egypt		22	20	42

Outcome Measures

1. Primary Outcome

Title	Number of Patients Diagnosed With Hirschsprung-associated Enterocolitis (HAEC).
Description	The primary outcome measure is reporting the number of participants diagnosed with Hirschsprung-associated enterocolitis (HAEC) after pullthrough procedure.
Time Frame	6 months post-pullthrough

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	VSL#3 Probiotic	Placebo
Arm/Group Description:	VSL#3: Dosing will be based on patient weight. For those infants greater or equal to 5 kg, one gram (360 billion bacteria or 4 sachets) of VSL#3 will be administered into 3 ounces of either expressed breast milk or formula daily. For patients under 5 kg, 0.5 gm (180 billion bacteria or 2 sachets) daily in the same amount of formula or breast milk. E.2.6. Time of start of probiotics: Probiotic vs. placebo will begin once the infant has reached full oral feeding.	Dosing will be based on patient weight. For those infants greater or equal to 5 kg, one gram (4 sachets) of placebo will be administered into 3 ounces of either expressed breast milk or formula daily. For patients under 5 kg, 0.5 gm (2 sachets) daily in the same amount of formula or breast milk Initiation: within one week of pullthrough Duration: 3 months Placebo: Dosing will be based on patient weight. For those infants greater or equal to 5 kg, one gram (4 sachets) of placebo will be administered into 3 ounces of either expressed breast milk or formula daily. For patients under 5 kg, 0.5 gm (2 sachets) daily in the same amount of formula or breast milk Initiation: within one week of pullthrough Duration: 3 months
Overall Number of Participants Analyzed	32	28
Measure Type: Number; Unit of Measure: participants
	10	7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	VSL#3 Probiotic, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	=0.897
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]

2. Primary Outcome

Title	Severity of Clinical Episodes of HAEC
Description	The severity of clinical episodes of HAEC will be stratified into three grades (mild, moderate, or severe). Grades of severity reported are based on first episodes.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	VSL#3 Probiotic	Placebo
Arm/Group Description:	VSL#3 : Dosing will be based on patient weight. For those infants greater or equal to 5 kg, one gram (360 billion bacteria or 4 sachets) of VSL#3 will be administered into 3 ounces of either expressed breast milk or formula daily. For patients under 5 kg, 0.5 gm (180 billion bacteria or 2 sachets) daily in the same amount of formula or breast milk. E.2.6. Time of start of probiotics: Probiotic vs. placebo will begin once the infant has reached full oral feeding.	Dosing will be based on patient weight. For those infants greater or equal to 5 kg, one gram (4 sachets) of placebo will be administered into 3 ounces of either expressed breast milk or formula daily. For patients under 5 kg, 0.5 gm (2 sachets) daily in the same amount of formula or breast milk Initiation: within one week of pullthrough Duration: 3 months Placebo : Dosing will be based on patient weight. For those infants greater or equal to 5 kg, one gram (4 sachets) of placebo will be administered into 3 ounces of either expressed breast milk or formula daily. For patients under 5 kg, 0.5 gm (2 sachets) daily in the same amount of formula or breast milk Initiation: within one week of pullthrough Duration: 3 months
Overall Number of Participants Analyzed	32	28
Measure Type: Number; Unit of Measure: participants
HAEC Severity, Mild	3	6
HAEC Severity, Moderate	6	0
HAEC Severity, Severe	1	1

Adverse Events

Time Frame	6 months
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	VSL#3 Probiotic	Placebo
Arm/Group Description	VSL#3 : Dosing will be based on patient weight. For those infants greater or equal to 5 kg, one gram (360 billion bacteria or 4 sachets) of VSL#3 will be administered into 3 ounces of either expressed breast milk or formula daily. For patients under 5 kg, 0.5 gm (180 billion bacteria or 2 sachets) daily in the same amount of formula or breast milk. E.2.6. Time of start of probiotics: Probiotic vs. placebo will begin once the infant has reached full oral feeding.	Dosing will be based on patient weight. For those infants greater or equal to 5 kg, one gram (4 sachets) of placebo will be administered into 3 ounces of either expressed breast milk or formula daily. For patients under 5 kg, 0.5 gm (2 sachets) daily in the same amount of formula or breast milk Initiation: within one week of pullthrough Duration: 3 months Placebo : Dosing will be based on patient weight. For those infants greater or equal to 5 kg, one gram (4 sachets) of placebo will be administered into 3 ounces of either expressed breast milk or formula daily. For patients under 5 kg, 0.5 gm (2 sachets) daily in the same amount of formula or breast milk Initiation: within one week of pullthrough Duration: 3 months
All-Cause Mortality
	VSL#3 Probiotic	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	VSL#3 Probiotic	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	10/32 (31.25%)	7/28 (25.00%)
Gastrointestinal disorders
Hirschsprung Associated Enterocolitis (HAEC)	10/32 (31.25%)	7/28 (25.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	VSL#3 Probiotic	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/32 (0.00%)	0/28 (0.00%)

Limitations and Caveats

The secondary outcome measure was defined before beginning the study as the measure of the expression of MUC-2 and MUC-3 expressed proteins in the stools of study patients. However, stool samples were not collected and this analysis was not done.

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.

Results Point of Contact

• Name/Title: Daniel Teitelabum
• Organization: University of Michigan
• Phone: 734-936-8464
• EMail: dttlbm@umich.edu

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

El-Sawaf M, Siddiqui S, Mahmoud M, Drongowski R, Teitelbaum DH. Probiotic prophylaxis after pullthrough for Hirschsprung disease to reduce incidence of enterocolitis: a prospective, randomized, double-blind, placebo-controlled, multicenter trial. J Pediatr Surg. 2013 Jan;48(1):111-7. doi: 10.1016/j.jpedsurg.2012.10.028.

• Responsible Party: Daniel H. Teitelbaum, University of Michigan
• ClinicalTrials.gov Identifier: NCT00630838
• Other Study ID Numbers: VSL-N007177
• First Submitted: February 28, 2008
• First Posted: March 7, 2008
• Results First Submitted: April 1, 2015
• Results First Posted: July 19, 2016
• Last Update Posted: July 19, 2016