Trial Outcomes & Findings for Probiotic Prophylaxis of Hirschprung's Disease Associated Enterocolitis (HAEC) (NCT NCT00630838)

NCT ID: NCT00630838

Last Updated: 2016-07-19

Results Overview

The primary outcome measure is reporting the number of participants diagnosed with Hirschsprung-associated enterocolitis (HAEC) after pullthrough procedure.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 62 participants
• Primary outcome timeframe: 6 months post-pullthrough
• Results posted on: 2016-07-19

Participant Flow

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

Participant milestones

Measure	VSL#3 Probiotic 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.	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 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 Study STARTED	32	30
Overall Study COMPLETED	32	28
Overall Study NOT COMPLETED	0	2

Reasons for withdrawal

Measure	VSL#3 Probiotic 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.	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 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 Study Death	0	1
Overall Study Lost to Follow-up	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	VSL#3 Probiotic n=32 Participants 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.	Placebo n=30 Participants 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 n=62 Participants Total of all reporting groups
Age, Categorical <=18 years	32 Participants n=5 Participants	30 Participants n=7 Participants	62 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	32 months STANDARD_DEVIATION 7.6 • n=5 Participants	28 months STANDARD_DEVIATION 4.9 • n=7 Participants	30 months STANDARD_DEVIATION 5.6 • n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants	5 Participants n=7 Participants	19 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants	25 Participants n=7 Participants	43 Participants n=5 Participants
Region of Enrollment United States	10 participants n=5 Participants	10 participants n=7 Participants	20 participants n=5 Participants
Region of Enrollment Egypt	22 participants n=5 Participants	20 participants n=7 Participants	42 participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months post-pullthrough

The primary outcome measure is reporting the number of participants diagnosed with Hirschsprung-associated enterocolitis (HAEC) after pullthrough procedure.

Outcome measures

Measure	VSL#3 Probiotic n=32 Participants 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.	Placebo n=28 Participants 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
Number of Patients Diagnosed With Hirschsprung-associated Enterocolitis (HAEC).	10 participants	7 participants

PRIMARY outcome

Timeframe: 6 months

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.

Outcome measures

Measure	VSL#3 Probiotic n=32 Participants 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.	Placebo n=28 Participants 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
Severity of Clinical Episodes of HAEC HAEC Severity, Mild	3 participants	6 participants
Severity of Clinical Episodes of HAEC HAEC Severity, Moderate	6 participants	0 participants
Severity of Clinical Episodes of HAEC HAEC Severity, Severe	1 participants	1 participants

Adverse Events

VSL#3 Probiotic

Serious events: 10 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 7 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	VSL#3 Probiotic n=32 participants at risk 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.	Placebo n=28 participants at risk 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
Gastrointestinal disorders Hirschsprung Associated Enterocolitis (HAEC)	31.2% 10/32 • 6 months	25.0% 7/28 • 6 months

Other adverse events

Adverse event data not reported

Additional Information

Daniel Teitelabum

University of Michigan

Phone: 734-936-8464

Email: dttlbm@umich.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place