Antibiotic Safety (SCAMP)

• Sponsor: Michael Cohen-Wolkowiez (Other)
• Overall Status: Completed
• CT.gov ID: NCT01994993
• Collaborator: The Emmes Company, LLC (Industry)
• Enrollment: 260
• Locations: 50
• Arms: 5
• Duration (Months): 40.6
• Patients Per Site: 5.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The main purpose of this study is evaluate whether it is safe or not to use various combination of antibiotics (ampicillin, metronidazole, clindamycin, piperacillin-tazobactam, gentamicin) in treating infants with complicated intra-abdominal infections

Condition or Disease	Intervention/Treatment	Phase
Complicated Intra Abdominal Infections	Drug: ampicillin and metronidazole and gentamicin; Drug: ampicillin and gentamicin and clindamycin; Drug: gentamicin and Piperacillin- tazobactam; Drug: standard of care antibiotics and metronidazole; Drug: metronidazole, clindamycin, or piperacillin-tazobactam	Phase 2/Phase 3

Detailed Description

The most commonly used antibiotics in infants with complicated intra-abdominal infections are not labeled for use in this population because safety and efficacy data are lacking. This study will provide the safety information required for labeling. In addition, the pharmacokinetics(PK) and effectiveness data will also be collected during this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 260 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Antibiotic Safety in Infants With Complicated Intra-Abdominal Infections (SCAMP Trial)
• Study Start Date: Dec 1, 2013
• Actual Primary Completion Date: Jan 15, 2017
• Actual Study Completion Date: Apr 20, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Group 1 (ampicillin +gentamycin +metronidazole) Ampicillin and gentamycin and metronidazole	Drug: ampicillin and metronidazole and gentamicin; IV infusion of ampicillin and metronidazole and gentamicin for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)
Active Comparator: Group 2 (ampicillin +gentamicin+clindamycin) ampicillin and gentamicin and clindamycin	Drug: ampicillin and gentamicin and clindamycin; IV infusion of ampicillin and gentamicin and clindamycin for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)
Active Comparator: Group 3 (piperacillin-tazobactam and gentamicin) piperacillin-tazobactam and gentamicin	Drug: gentamicin and Piperacillin- tazobactam; IV infusion of gentamicin and Piperacillin- tazobactam for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)
Active Comparator: Group 4 (metronidazole) Per standard of care antibiotics, and Metronidazole	Drug: standard of care antibiotics and metronidazole; IV infusion of standard of care antibiotics and metronidazole for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)
Active Comparator: Group 5 (metronidazole/clindamycin/piperacillin-tazobactam) metronidazole, clindamycin, or piperacillin-tazobactam	Drug: metronidazole, clindamycin, or piperacillin-tazobactam; IV infusion of metronidazole, clindamycin, or piperacillin-tazobactam with scheduled CSF procedures per standard of care. Study drug will be given for for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)

Outcome Measures

Primary Outcome Measures

1. Death [Within 30 days after last dose of study drug, up to 40 days]

   Number of Participants who experienced Death

Secondary Outcome Measures

1. Number of Participants With Therapeutic Success at Day 30 [30 days after last dose of study drug]

   Confirmed by 1).Alive, 2).Negative bacterial blood cultures, and 3). Clinical cure score >4. Clinical cure score =1 for each of the following elements: FiO2 ≤ baseline FiO2; Urine output ≥1 mL/kg/h for 24-hour period prior to assessment; Absence of inotropic support at time of assessment; Absence of mechanical ventilation at time of assessment; No seizure in 24-hour period prior to assessment; pH ≥7.25 or not measured in 24 hours prior to assessment

Other Outcome Measures

1. Number of Participants With Feeding Intolerance [90 days after last dose of study drug]

   Feeding intolerance confirmed by documentation of any feedings held for >24 consecutive hours in infants being fed

2. Number of Participants With Grade 3 and/or Grade 4 Intraventricular Hemorrhage (IVH) [90 days after last dose of study drug]

   Grade 3 IVH: Subependymal hemorrhage with extension into lateral ventricles with ventricular enlargement Grade 4 IVH: Intraparenchymal hemorrhage

3. Number of Participants With Short Bowel Syndrome [90 days after last dose of study drug]

   Short bowel syndrome: Operative reports documenting resection of bowel, estimated bowel length, and absence/presence of the ileocecal valve. Total parenteral nutrition for >42 consecutive days after bowel resection, or a residual small bowel length of less than 25% expected for gestational age

4. Number of Participants With Intestinal Perforation [90 days after last dose of study drug]

   Intestinal perforation: Radiological reports leading to the diagnosis of intestinal perforation. These include plain chest x-rays, plain abdominal x-rays, ultra-sonograms of the abdomen, contrast studies, and computed tomography scans of the abdomen and pelvis. Operative reports documenting surgical procedures leading to the diagnosis and/or treatment of intestinal perforation. These include placement of a surgical drain, laparotomy, intestinal resection, and ostomy placement

5. Number of Participants With Intestinal Stricture [90 days after last dose of study drug]

   Intestinal stricture: Radiology reports leading to the diagnosis of intestinal stricture. These include plain abdominal x-rays, upper gastrointestinal series with small bowel follow-through, contrast enema studies, and computed tomography scans of the abdomen and pelvis. Operative reports documenting surgical procedures leading to the diagnosis and/or treatment of intestinal stricture. These procedures include endoscopy, laparotomy, stricture dilatation, intestinal resection, and ostomy placement

6. Number of Participants Progressed to a Higher Stage of Necrotizing Enterocolitis (NEC), if NEC is the Cause of the Complicated Intra-abdominal Infection [90 days after last dose of study drug]

   Progression is determined by the clinical NEC scoring

7. Number of Participants With Gastrointestinal Surgeries [90 days after last dose of study drug]

   Determined by medical history and confirmed with hospital records. (Laparotomy)

8. Number of Participants With Seizure [90 days after last dose of study drug]

   documented seizure(s) in hospital records

9. Number of Participants With Positive Blood Cultures [90 days after last dose of study drug]

   Positive blood culture (bacterial or fungal)

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 120 Days
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Informed consent obtained from parent(s) or legal guardian(s) (Groups 1-5)

2. ≤33 weeks gestation at birth (Groups 1-3, 5)

3. ≥34 weeks gestation at birth (Groups 4 and 5)

4. PNA <121 days (Groups 1-5)

5. Sufficient venous access to permit administration of study drug (intravenous [IV]) (Groups 1-5)

6. Presenting physical, radiological, and/or bacteriological findings of a complicated intra-abdominal infection within 48 hours prior to randomization/first study drug dose (Groups 1-4)**. Complicated intra-abdominal infections include secondary peritonitis, NEC grade II or higher by Bell's criteria, Hirschsprung's disease with perforation, spontaneous intestinal perforation, meconium ileus with perforation, bowel obstruction with perforation, gastroschisis with necrosis and/or perforation, omphalocele with necrosis and/or perforation, neonatal appendicitis, intestinal pneumatosis or portal venous gas, free peritoneal air on abdominal radiographic examination, or abdominal abscess.

7. Suspected or confirmed infection for which the study drug may provide therapeutic benefit and planned CSF collection per standard of care (Group 5).

Exclusion Criteria*

1. History of anaphylaxis in response to study drugs (Groups 1-5)

2. Serum creatinine >2 mg/dL within 48 hours on measurement prior to and closest to randomization /first study drug dose (Groups 1- 5)**

3. Known ALT >250 U/L or AST >500 U/L on measurement closest to the time of randomization or first study drug dose (Groups 1-5)**

4. Any condition that, in the judgment of the investigator, precludes participation because it could affect participant safety (Groups 1-5)

• Do not apply for Group 5 participants receiving drug per standard of care

• Criteria must be satisfied by randomization (randomized Groups 1-3) or first study drug dose (non-randomized Groups 1-3, Group 4 and Group 5), whichever comes first.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35233
2	Arkansas Children's Hospital/Univ of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72202
3	Loma Linda University Medical Center	Loma Linda	California	United States	92354
4	Stanford University School of Medicine	Palo Alto	California	United States	94304
5	Rady Children's Hospital and Health Center	San Diego	California	United States	92123
6	University of California San Diego Medical Center	San Diego	California	United States	92123
7	Sharp Mary Birch	San Diego	California	United States	92131
8	Connecticut Children's Medical Center	Hartford	Connecticut	United States	06106
9	University of Florida Jacksonville Healthcare, Inc.	Jacksonville	Florida	United States	32209
10	Wolfson Children's Hospital, Shands Medical Center	Jacksonville	Florida	United States	32209
11	Georgia Regents University	Augusta	Georgia	United States	30912
12	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii	United States	96826
13	Riley Hospital	Indianapolis	Indiana	United States	46202
14	Wesley Medical Center	Wichita	Kansas	United States	67214
15	University of Kentucky Hospital	Lexington	Kentucky	United States	40536
16	Louisana State University Health Sciences Center	Shreveport	Louisiana	United States	71103
17	University of Maryland Hospital	Baltimore	Maryland	United States	21201
18	Floating Hospital for Children at Tufts Medical Center	Boston	Massachusetts	United States	02111
19	University of Minnesota Fairview University Medical Center	Minneapolis	Minnesota	United States	55455
20	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
21	Kings County Hospital	Brooklyn	New York	United States	11203
22	Brookdale University Hospital	Brooklyn	New York	United States	11212
23	New York University School of Medicine	New York	New York	United States	10016
24	Columbia University Neonatology	New York	New York	United States	10032
25	Westchester Medical Center - New York Medical College	Valhalla	New York	United States	10595
26	University of North Carolina Hospital	Chapel Hill	North Carolina	United States	27514
27	Levine Children's Hospital	Charlotte	North Carolina	United States	28232
28	Duke University Medical Center	Durham	North Carolina	United States	27710
29	East Carolina University	Greenville	North Carolina	United States	27834
30	WakeMed Faculty Neonatology	Raleigh	North Carolina	United States	27610
31	New Hanover Reginal Medical Center	Wilmington	North Carolina	United States	28403
32	Wake Forest University School of Medicine	Winston-Salem	North Carolina	United States	27157
33	Cincinnati Children's Hospital	Cincinnati	Ohio	United States	45229
34	Rainbow Babies and Children's Hospital	Cleveland	Ohio	United States	44106
35	University of Oklahoma Health Science Center	Oklahoma City	Oklahoma	United States	73104
36	Penn State Hershey Children's Hospital	Hershey	Pennsylvania	United States	17033
37	Womens and Infant Hospital of Rhode Island	Providence	Rhode Island	United States	02905
38	Medical University of South Carolina	Charleston	South Carolina	United States	29425
39	Vanderbilt University	Nashville	Tennessee	United States	37232
40	Texas Children's Hospital	Houston	Texas	United States	77030
41	University of Texas Health Science Center at Houston	Houston	Texas	United States	77030
42	Intermountain Medical Center	Salt Lake City	Utah	United States	84108
43	University of Utah	Salt Lake City	Utah	United States	84132
44	University of Virginia Health System	Charlottesville	Virginia	United States	22908
45	Carilion Roanoke Memorial Hospital	Roanoke	Virginia	United States	24014
46	University of Alberta - Royal Alexandra Hospital	Edmonton	Alberta	Canada	T5H 3V9
47	University of British Columbia - British Columbia Women's Hospital	Vancouver	British Columbia	Canada	V6H 3V4
48	Manitoba Institute of Child Health	Winnipeg	Manitoba	Canada	R3P 2C1
49	Children's Hospital of Eastern Ontario	Ottawa	Ontario	Canada	K1H 8L1
50	Hospital Sainte-Justine	Montreal	Quebec	Canada	T3T 1C5

Sponsors and Collaborators

• Michael Cohen-Wolkowiez
• The Emmes Company, LLC

Investigators

• Principal Investigator: Micheal Cohen-Wolkowiez, MD, PhD, Duke University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Michael Cohen-Wolkowiez, Associate Professor, Duke University
• ClinicalTrials.gov Identifier: NCT01994993
• Other Study ID Numbers: Pro00048773; HHSN275201000003I
• First Posted: Nov 26, 2013
• Last Update Posted: May 30, 2019
• Last Verified: May 1, 2019

• Keywords provided by Michael Cohen-Wolkowiez, Associate Professor, Duke University: Antibiotics; ampicillin; metronidazole; clindamycin; piperacillin-tazobactam; Safety; Infants; Intra abdominal infections
• Additional relevant MeSH terms: Infections; Intraabdominal Infections; Anti-Bacterial Agents; Metronidazole; Clindamycin; Clindamycin palmitate; Clindamycin phosphate; Gentamicins; Tazobactam; Piperacillin; Ampicillin; Piperacillin, Tazobactam Drug Combination

Study Results

Participant Flow

Pre-assignment Detail	One participant was enrolled but did not receive any dose of study drug. The participant is excluded from study result data analysis

Arm/Group Title	Group 1	Group 2	Group 3	Group 4	Group 5
Arm/Group Description	Ampicillin and gentamycin and metronidazole ampicillin and metronidazole and gentamicin: IV infusion of ampicillin and metronidazole and gentamicin for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)	ampicillin and gentamicin and clindamycin ampicillin and gentamicin and clindamycin: IV infusion of ampicillin and gentamicin and clindamycin for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)	piperacillin-tazobactam and gentamicin gentamicin and Piperacillin- tazobactam: IV infusion of gentamicin and Piperacillin- tazobactam for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)	Per standard of care antibiotics, and Metronidazole standard of care antibiotics and metronidazole: IV infusion of standard of care antibiotics and metronidazole for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)	metronidazole, clindamycin, or piperacillin-tazobactam metronidazole, clindamycin, or piperacillin-tazobactam: IV infusion of metronidazole, clindamycin, or piperacillin-tazobactam with scheduled CSF procedures per standard of care. Study drug will be given for for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)
Period Title: Overall Study
STARTED	63	47	70	55	24
COMPLETED	28	12	23	9	22
NOT COMPLETED	35	35	47	46	2

Baseline Characteristics

Arm/Group Title	Group 1	Group 2	Group 3	Group 4	Group 5	Total
Arm/Group Description	Ampicillin and gentamycin and metronidazole ampicillin and metronidazole and gentamicin: IV infusion of ampicillin and metronidazole and gentamicin for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)	ampicillin and gentamicin and clindamycin ampicillin and gentamicin and clindamycin: IV infusion of ampicillin and gentamicin and clindamycin for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)	piperacillin-tazobactam and gentamicin gentamicin and Piperacillin- tazobactam: IV infusion of gentamicin and Piperacillin- tazobactam for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)	Per standard of care antibiotics, and Metronidazole standard of care antibiotics and metronidazole: IV infusion of standard of care antibiotics and metronidazole for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)	metronidazole, clindamycin, or piperacillin-tazobactam metronidazole, clindamycin, or piperacillin-tazobactam: IV infusion of metronidazole, clindamycin, or piperacillin-tazobactam with scheduled CSF procedures per standard of care. Study drug will be given for for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)	Total of all reporting groups
Overall Participants	62	46	70	55	24	257
Age (Gestational Age (weeks)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Gestational Age (weeks)]	27.3 (2.6)	27.8 (3.0)	27.5 (2.9)	36.4 (2.1)	28.9 (4.9)	29.5 (4.6)
Sex: Female, Male (Count of Participants)
Female	18 29%	17 37%	42 60%	27 49.1%	10 41.7%	114 44.4%
Male	44 71%	29 63%	28 40%	28 50.9%	14 58.3%	143 55.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	12 19.4%	11 23.9%	11 15.7%	12 21.8%	1 4.2%	47 18.3%
Not Hispanic or Latino	46 74.2%	34 73.9%	52 74.3%	38 69.1%	20 83.3%	190 73.9%
Unknown or Not Reported	4 6.5%	1 2.2%	7 10%	5 9.1%	3 12.5%	20 7.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 1.6%	0 0%	0 0%	1 1.8%	0 0%	2 0.8%
Asian	0 0%	1 2.2%	1 1.4%	1 1.8%	0 0%	3 1.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	20 32.3%	10 21.7%	23 32.9%	8 14.5%	6 25%	67 26.1%
White	32 51.6%	26 56.5%	37 52.9%	35 63.6%	14 58.3%	144 56%
More than one race	2 3.2%	1 2.2%	4 5.7%	1 1.8%	2 8.3%	10 3.9%
Unknown or Not Reported	7 11.3%	8 17.4%	5 7.1%	9 16.4%	2 8.3%	31 12.1%
Region of Enrollment (count of participants) [Number]
Canada	4 6.5%	0 0%	0 0%	0 0%	1 4.2%	5 1.9%
United States	58 93.5%	46 100%	70 100%	55 100%	23 95.8%	252 98.1%

Outcome Measures

1. Primary Outcome

Title	Death
Description	Number of Participants who experienced Death
Time Frame	Within 30 days after last dose of study drug, up to 40 days

Outcome Measure Data

Analysis Population Description

Full intent-to-treat population (patients who received at least 1 dose of any study drug)

Arm/Group Title	Group 1	Group 2	Group 3	Group 4	Group 5
Arm/Group Description	Ampicillin and gentamycin and metronidazole ampicillin and metronidazole and gentamicin: IV infusion of ampicillin and metronidazole and gentamicin for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)	ampicillin and gentamicin and clindamycin ampicillin and gentamicin and clindamycin: IV infusion of ampicillin and gentamicin and clindamycin for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)	piperacillin-tazobactam and gentamicin gentamicin and Piperacillin- tazobactam: IV infusion of gentamicin and Piperacillin- tazobactam for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)	Per standard of care antibiotics, and Metronidazole standard of care antibiotics and metronidazole: IV infusion of standard of care antibiotics and metronidazole for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)	metronidazole, clindamycin, or piperacillin-tazobactam metronidazole, clindamycin, or piperacillin-tazobactam: IV infusion of metronidazole, clindamycin, or piperacillin-tazobactam with scheduled CSF procedures per standard of care. Study drug will be given for for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)
Measure Participants	63	47	70	56	24
Count of Participants [Participants]	5 8.1%	5 10.9%	7 10%	1 1.8%	0 0%

2. Secondary Outcome

Title	Number of Participants With Therapeutic Success at Day 30
Description	Confirmed by 1).Alive, 2).Negative bacterial blood cultures, and 3). Clinical cure score >4. Clinical cure score =1 for each of the following elements: FiO2 ≤ baseline FiO2; Urine output ≥1 mL/kg/h for 24-hour period prior to assessment; Absence of inotropic support at time of assessment; Absence of mechanical ventilation at time of assessment; No seizure in 24-hour period prior to assessment; pH ≥7.25 or not measured in 24 hours prior to assessment
Time Frame	30 days after last dose of study drug

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of each study drug. Does not apply to Group 5.

Arm/Group Title	Group 1	Group 2	Group 3	Group 4
Arm/Group Description	Ampicillin and gentamycin and metronidazole ampicillin and metronidazole and gentamicin: IV infusion of ampicillin and metronidazole and gentamicin for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)	ampicillin and gentamicin and clindamycin ampicillin and gentamicin and clindamycin: IV infusion of ampicillin and gentamicin and clindamycin for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)	piperacillin-tazobactam and gentamicin gentamicin and Piperacillin- tazobactam: IV infusion of gentamicin and Piperacillin- tazobactam for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)	Per standard of care antibiotics, and Metronidazole standard of care antibiotics and metronidazole: IV infusion of standard of care antibiotics and metronidazole for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)
Measure Participants	62	46	70	55
Count of Participants [Participants]	45 72.6%	39 84.8%	52 74.3%	52 94.5%

3. Other Pre-specified Outcome

Title	Number of Participants With Feeding Intolerance
Description	Feeding intolerance confirmed by documentation of any feedings held for >24 consecutive hours in infants being fed
Time Frame	90 days after last dose of study drug

Outcome Measure Data

Analysis Population Description

Participant who received at least 1 dose of each study drug

Arm/Group Title	Group 1	Group 2	Group 3	Group 4
Arm/Group Description	Ampicillin and gentamycin and metronidazole ampicillin and metronidazole and gentamicin: IV infusion of ampicillin and metronidazole and gentamicin for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)	ampicillin and gentamicin and clindamycin ampicillin and gentamicin and clindamycin: IV infusion of ampicillin and gentamicin and clindamycin for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)	piperacillin-tazobactam and gentamicin gentamicin and Piperacillin- tazobactam: IV infusion of gentamicin and Piperacillin- tazobactam for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)	Per standard of care antibiotics, and Metronidazole standard of care antibiotics and metronidazole: IV infusion of standard of care antibiotics and metronidazole for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)
Measure Participants	62	46	70	55
Count of Participants [Participants]	24 38.7%	19 41.3%	21 30%	18 32.7%

4. Other Pre-specified Outcome

Title	Number of Participants With Grade 3 and/or Grade 4 Intraventricular Hemorrhage (IVH)
Description	Grade 3 IVH: Subependymal hemorrhage with extension into lateral ventricles with ventricular enlargement Grade 4 IVH: Intraparenchymal hemorrhage
Time Frame	90 days after last dose of study drug

Outcome Measure Data

Analysis Population Description

Participant who received at least 1 dose of each study drug

Arm/Group Title	Group 1	Group 2	Group 3	Group 4
Arm/Group Description	Ampicillin and gentamycin and metronidazole ampicillin and metronidazole and gentamicin: IV infusion of ampicillin and metronidazole and gentamicin for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)	ampicillin and gentamicin and clindamycin ampicillin and gentamicin and clindamycin: IV infusion of ampicillin and gentamicin and clindamycin for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)	piperacillin-tazobactam and gentamicin gentamicin and Piperacillin- tazobactam: IV infusion of gentamicin and Piperacillin- tazobactam for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)	Per standard of care antibiotics, and Metronidazole standard of care antibiotics and metronidazole: IV infusion of standard of care antibiotics and metronidazole for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)
Measure Participants	62	46	70	55
Count of Participants [Participants]	2 3.2%	4 8.7%	4 5.7%	0 0%

5. Other Pre-specified Outcome

Title	Number of Participants With Short Bowel Syndrome
Description	Short bowel syndrome: Operative reports documenting resection of bowel, estimated bowel length, and absence/presence of the ileocecal valve. Total parenteral nutrition for >42 consecutive days after bowel resection, or a residual small bowel length of less than 25% expected for gestational age
Time Frame	90 days after last dose of study drug

Outcome Measure Data

Analysis Population Description

Participant who received at least 1 dose of each study drug

Arm/Group Title	Group 1	Group 2	Group 3	Group 4
Arm/Group Description	Ampicillin and gentamycin and metronidazole ampicillin and metronidazole and gentamicin: IV infusion of ampicillin and metronidazole and gentamicin for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)	ampicillin and gentamicin and clindamycin ampicillin and gentamicin and clindamycin: IV infusion of ampicillin and gentamicin and clindamycin for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)	piperacillin-tazobactam and gentamicin gentamicin and Piperacillin- tazobactam: IV infusion of gentamicin and Piperacillin- tazobactam for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)	Per standard of care antibiotics, and Metronidazole standard of care antibiotics and metronidazole: IV infusion of standard of care antibiotics and metronidazole for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)
Measure Participants	62	46	70	55
Count of Participants [Participants]	5 8.1%	3 6.5%	1 1.4%	1 1.8%

6. Other Pre-specified Outcome

Title	Number of Participants With Intestinal Perforation
Description	Intestinal perforation: Radiological reports leading to the diagnosis of intestinal perforation. These include plain chest x-rays, plain abdominal x-rays, ultra-sonograms of the abdomen, contrast studies, and computed tomography scans of the abdomen and pelvis. Operative reports documenting surgical procedures leading to the diagnosis and/or treatment of intestinal perforation. These include placement of a surgical drain, laparotomy, intestinal resection, and ostomy placement
Time Frame	90 days after last dose of study drug

Outcome Measure Data

Analysis Population Description

Participant who received at least 1 dose of each study drug

Arm/Group Title	Group 1	Group 2	Group 3	Group 4
Arm/Group Description	Ampicillin and gentamycin and metronidazole ampicillin and metronidazole and gentamicin: IV infusion of ampicillin and metronidazole and gentamicin for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)	ampicillin and gentamicin and clindamycin ampicillin and gentamicin and clindamycin: IV infusion of ampicillin and gentamicin and clindamycin for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)	piperacillin-tazobactam and gentamicin gentamicin and Piperacillin- tazobactam: IV infusion of gentamicin and Piperacillin- tazobactam for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)	Per standard of care antibiotics, and Metronidazole standard of care antibiotics and metronidazole: IV infusion of standard of care antibiotics and metronidazole for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)
Measure Participants	62	46	70	55
Count of Participants [Participants]	2 3.2%	4 8.7%	2 2.9%	1 1.8%

7. Other Pre-specified Outcome

Title	Number of Participants With Intestinal Stricture
Description	Intestinal stricture: Radiology reports leading to the diagnosis of intestinal stricture. These include plain abdominal x-rays, upper gastrointestinal series with small bowel follow-through, contrast enema studies, and computed tomography scans of the abdomen and pelvis. Operative reports documenting surgical procedures leading to the diagnosis and/or treatment of intestinal stricture. These procedures include endoscopy, laparotomy, stricture dilatation, intestinal resection, and ostomy placement
Time Frame	90 days after last dose of study drug

Outcome Measure Data

Analysis Population Description

Participant who received at least 1 dose of each study drug

Arm/Group Title	Group 1	Group 2	Group 3	Group 4
Arm/Group Description	Ampicillin and gentamycin and metronidazole ampicillin and metronidazole and gentamicin: IV infusion of ampicillin and metronidazole and gentamicin for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)	ampicillin and gentamicin and clindamycin ampicillin and gentamicin and clindamycin: IV infusion of ampicillin and gentamicin and clindamycin for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)	piperacillin-tazobactam and gentamicin gentamicin and Piperacillin- tazobactam: IV infusion of gentamicin and Piperacillin- tazobactam for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)	Per standard of care antibiotics, and Metronidazole standard of care antibiotics and metronidazole: IV infusion of standard of care antibiotics and metronidazole for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)
Measure Participants	62	46	70	55
Count of Participants [Participants]	3 4.8%	2 4.3%	4 5.7%	1 1.8%

8. Other Pre-specified Outcome

Title	Number of Participants Progressed to a Higher Stage of Necrotizing Enterocolitis (NEC), if NEC is the Cause of the Complicated Intra-abdominal Infection
Description	Progression is determined by the clinical NEC scoring
Time Frame	90 days after last dose of study drug

Outcome Measure Data

Analysis Population Description

Participant who received at least 1 dose of each study drug

Arm/Group Title	Group 1	Group 2	Group 3	Group 4
Arm/Group Description	Ampicillin and gentamycin and metronidazole ampicillin and metronidazole and gentamicin: IV infusion of ampicillin and metronidazole and gentamicin for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)	ampicillin and gentamicin and clindamycin ampicillin and gentamicin and clindamycin: IV infusion of ampicillin and gentamicin and clindamycin for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)	piperacillin-tazobactam and gentamicin gentamicin and Piperacillin- tazobactam: IV infusion of gentamicin and Piperacillin- tazobactam for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)	Per standard of care antibiotics, and Metronidazole standard of care antibiotics and metronidazole: IV infusion of standard of care antibiotics and metronidazole for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)
Measure Participants	62	46	70	55
Count of Participants [Participants]	1 1.6%	2 4.3%	0 0%	1 1.8%

9. Other Pre-specified Outcome

Title	Number of Participants With Gastrointestinal Surgeries
Description	Determined by medical history and confirmed with hospital records. (Laparotomy)
Time Frame	90 days after last dose of study drug

Outcome Measure Data

Analysis Population Description

Participant who received at least 1 dose of each study drug

Arm/Group Title	Group 1	Group 2	Group 3	Group 4
Arm/Group Description	Ampicillin and gentamycin and metronidazole ampicillin and metronidazole and gentamicin: IV infusion of ampicillin and metronidazole and gentamicin for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)	ampicillin and gentamicin and clindamycin ampicillin and gentamicin and clindamycin: IV infusion of ampicillin and gentamicin and clindamycin for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)	piperacillin-tazobactam and gentamicin gentamicin and Piperacillin- tazobactam: IV infusion of gentamicin and Piperacillin- tazobactam for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)	Per standard of care antibiotics, and Metronidazole standard of care antibiotics and metronidazole: IV infusion of standard of care antibiotics and metronidazole for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)
Measure Participants	62	46	70	55
Count of Participants [Participants]	27 43.5%	15 32.6%	26 37.1%	10 18.2%

10. Other Pre-specified Outcome

Title	Number of Participants With Seizure
Description	documented seizure(s) in hospital records
Time Frame	90 days after last dose of study drug

Outcome Measure Data

Analysis Population Description

Participant who received at least 1 dose of each study drug

Arm/Group Title	Group 1	Group 2	Group 3	Group 4
Arm/Group Description	Ampicillin and gentamycin and metronidazole ampicillin and metronidazole and gentamicin: IV infusion of ampicillin and metronidazole and gentamicin for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)	ampicillin and gentamicin and clindamycin ampicillin and gentamicin and clindamycin: IV infusion of ampicillin and gentamicin and clindamycin for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)	piperacillin-tazobactam and gentamicin gentamicin and Piperacillin- tazobactam: IV infusion of gentamicin and Piperacillin- tazobactam for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)	Per standard of care antibiotics, and Metronidazole standard of care antibiotics and metronidazole: IV infusion of standard of care antibiotics and metronidazole for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)
Measure Participants	62	46	70	55
Count of Participants [Participants]	4 6.5%	0 0%	2 2.9%	1 1.8%

11. Other Pre-specified Outcome

Title	Number of Participants With Positive Blood Cultures
Description	Positive blood culture (bacterial or fungal)
Time Frame	90 days after last dose of study drug

Outcome Measure Data

Analysis Population Description

Participant who received at least 1 dose of each study drug

Arm/Group Title	Group 1	Group 2	Group 3	Group 4
Arm/Group Description	Ampicillin and gentamycin and metronidazole ampicillin and metronidazole and gentamicin: IV infusion of ampicillin and metronidazole and gentamicin for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)	ampicillin and gentamicin and clindamycin ampicillin and gentamicin and clindamycin: IV infusion of ampicillin and gentamicin and clindamycin for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)	piperacillin-tazobactam and gentamicin gentamicin and Piperacillin- tazobactam: IV infusion of gentamicin and Piperacillin- tazobactam for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)	Per standard of care antibiotics, and Metronidazole standard of care antibiotics and metronidazole: IV infusion of standard of care antibiotics and metronidazole for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)
Measure Participants	62	46	70	55
Count of Participants [Participants]	8 12.9%	4 8.7%	12 17.1%	5 9.1%

Adverse Events

Time Frame	90 days post last study dose
Adverse Event Reporting Description	Note: Participants who received at least 1 dose of any study drug in the randomized or assigned protocol treatment group were included in the intention-to-treat (ITT) population used for the safety and efficacy analyses
Arm/Group Title	Group 1		Group 2		Group 3		Group 4		Group 5
Arm/Group Description	Ampicillin and gentamycin and metronidazole ampicillin and metronidazole and gentamicin: IV infusion of ampicillin and metronidazole and gentamicin for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)		ampicillin and gentamicin and clindamycin ampicillin and gentamicin and clindamycin: IV infusion of ampicillin and gentamicin and clindamycin for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)		piperacillin-tazobactam and gentamicin gentamicin and Piperacillin- tazobactam: IV infusion of gentamicin and Piperacillin- tazobactam for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)		Per standard of care antibiotics, and Metronidazole standard of care antibiotics and metronidazole: IV infusion of standard of care antibiotics and metronidazole for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)		metronidazole, clindamycin, or piperacillin-tazobactam metronidazole, clindamycin, or piperacillin-tazobactam: IV infusion of metronidazole, clindamycin, or piperacillin-tazobactam with scheduled CSF procedures per standard of care. Study drug will be given for for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)
All Cause Mortality
	Group 1		Group 2		Group 3		Group 4		Group 5
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/62 (8.1%)		5/46 (10.9%)		7/70 (10%)		1/55 (1.8%)		0/24 (0%)
Serious Adverse Events
	Group 1		Group 2		Group 3		Group 4		Group 5
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/62 (30.6%)		10/46 (21.7%)		12/70 (17.1%)		3/55 (5.5%)		3/24 (12.5%)
Cardiac disorders
Cardiac arrest	1/62 (1.6%)	1	0/46 (0%)	0	0/70 (0%)	0	0/55 (0%)	0	0/24 (0%)	0
Cardiopulmonary failure	0/62 (0%)	0	0/46 (0%)	0	0/70 (0%)	0	1/55 (1.8%)	1	0/24 (0%)	0
Congenital, familial and genetic disorders
Patent ductus arteriosus	1/62 (1.6%)	1	0/46 (0%)	0	1/70 (1.4%)	1	0/55 (0%)	0	0/24 (0%)	0
Eye disorders
Retinal detachment	0/62 (0%)	0	0/46 (0%)	0	0/70 (0%)	0	1/55 (1.8%)	1	0/24 (0%)	0
Retinopathy of prematurity	1/62 (1.6%)	1	0/46 (0%)	0	0/70 (0%)	0	0/55 (0%)	0	0/24 (0%)	0
Gastrointestinal disorders
Gastrointestinal necrosis	1/62 (1.6%)	1	0/46 (0%)	0	0/70 (0%)	0	0/55 (0%)	0	0/24 (0%)	0
Necrotising colitis	1/62 (1.6%)	1	1/46 (2.2%)	1	0/70 (0%)	0	0/55 (0%)	0	0/24 (0%)	0
Oesophageal perforation	1/62 (1.6%)	1	0/46 (0%)	0	0/70 (0%)	0	0/55 (0%)	0	0/24 (0%)	0
General disorders
Organ failure	0/62 (0%)	0	0/46 (0%)	0	1/70 (1.4%)	1	0/55 (0%)	0	0/24 (0%)	0
Infections and infestations
Bacterial sepsis	1/62 (1.6%)	1	0/46 (0%)	0	1/70 (1.4%)	1	0/55 (0%)	0	0/24 (0%)	0
Candida infection	0/62 (0%)	0	1/46 (2.2%)	1	0/70 (0%)	0	0/55 (0%)	0	0/24 (0%)	0
Candida sepsis	1/62 (1.6%)	1	1/46 (2.2%)	1	0/70 (0%)	0	0/55 (0%)	0	0/24 (0%)	0
Cytomegalovirus infection	1/62 (1.6%)	1	0/46 (0%)	0	0/70 (0%)	0	0/55 (0%)	0	0/24 (0%)	0
Enterococcal sepsis	0/62 (0%)	0	0/46 (0%)	0	1/70 (1.4%)	1	0/55 (0%)	0	0/24 (0%)	0
Escherichia infection	1/62 (1.6%)	1	0/46 (0%)	0	0/70 (0%)	0	0/55 (0%)	0	0/24 (0%)	0
Escherichia sepsis	0/62 (0%)	0	0/46 (0%)	0	1/70 (1.4%)	1	0/55 (0%)	0	0/24 (0%)	0
Fungal endocarditis	0/62 (0%)	0	1/46 (2.2%)	1	0/70 (0%)	0	0/55 (0%)	0	0/24 (0%)	0
Fungal infection	0/62 (0%)	0	0/46 (0%)	0	1/70 (1.4%)	1	0/55 (0%)	0	0/24 (0%)	0
Pneumonia	1/62 (1.6%)	1	0/46 (0%)	0	0/70 (0%)	0	0/55 (0%)	0	0/24 (0%)	0
Pseudomonal bacteraemia	0/62 (0%)	0	1/46 (2.2%)	1	0/70 (0%)	0	0/55 (0%)	0	0/24 (0%)	0
Pseudomonal sepsis	0/62 (0%)	0	0/46 (0%)	0	1/70 (1.4%)	1	0/55 (0%)	0	0/24 (0%)	0
Sepsis	0/62 (0%)	0	0/46 (0%)	0	1/70 (1.4%)	1	0/55 (0%)	0	0/24 (0%)	0
Septic shock	1/62 (1.6%)	1	0/46 (0%)	0	0/70 (0%)	0	0/55 (0%)	0	0/24 (0%)	0
Staphylococcal sepsis	0/62 (0%)	0	0/46 (0%)	0	1/70 (1.4%)	1	0/55 (0%)	0	0/24 (0%)	0
Injury, poisoning and procedural complications
Endotracheal intubation complication	1/62 (1.6%)	1	0/46 (0%)	0	0/70 (0%)	0	0/55 (0%)	0	0/24 (0%)	0
Nervous system disorders
Encephalopathy	0/62 (0%)	0	1/46 (2.2%)	1	0/70 (0%)	0	0/55 (0%)	0	0/24 (0%)	0
Haemorrhage intracranial	0/62 (0%)	0	0/46 (0%)	0	1/70 (1.4%)	1	0/55 (0%)	0	0/24 (0%)	0
Hydrocephalus	1/62 (1.6%)	1	0/46 (0%)	0	0/70 (0%)	0	0/55 (0%)	0	0/24 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	0/62 (0%)	0	1/46 (2.2%)	1	0/70 (0%)	0	0/55 (0%)	0	0/24 (0%)	0
Infantile apnoea	0/62 (0%)	0	0/46 (0%)	0	0/70 (0%)	0	1/55 (1.8%)	1	0/24 (0%)	0
Neonatal respiratory failure	0/62 (0%)	0	1/46 (2.2%)	1	0/70 (0%)	0	0/55 (0%)	0	0/24 (0%)	0
Pleural effusion	0/62 (0%)	0	0/46 (0%)	0	0/70 (0%)	0	0/55 (0%)	0	1/24 (4.2%)	1
Pneumothorax	1/62 (1.6%)	1	0/46 (0%)	0	1/70 (1.4%)	1	0/55 (0%)	0	0/24 (0%)	0
Respiratory distress	1/62 (1.6%)	1	0/46 (0%)	0	0/70 (0%)	0	0/55 (0%)	0	0/24 (0%)	0
Respiratory failure	0/62 (0%)	0	1/46 (2.2%)	1	0/70 (0%)	0	0/55 (0%)	0	1/24 (4.2%)	1
Surgical and medical procedures
Debridement	0/62 (0%)	0	0/46 (0%)	0	0/70 (0%)	0	0/55 (0%)	0	1/24 (4.2%)	1
Patent ductus arteriosus repair	1/62 (1.6%)	1	1/46 (2.2%)	1	0/70 (0%)	0	0/55 (0%)	0	0/24 (0%)	0
Vascular disorders
Extremity necrosis	1/62 (1.6%)	1	0/46 (0%)	0	0/70 (0%)	0	0/55 (0%)	0	0/24 (0%)	0
Hypotension	1/62 (1.6%)	1	0/46 (0%)	0	0/70 (0%)	0	0/55 (0%)	0	0/24 (0%)	0
Shock haemorrhagic	1/62 (1.6%)	1	0/46 (0%)	0	0/70 (0%)	0	0/55 (0%)	0	0/24 (0%)	0
Venous occlusion	0/62 (0%)	0	0/46 (0%)	0	1/70 (1.4%)	1	0/55 (0%)	0	0/24 (0%)	0
Other (Not Including Serious) Adverse Events
	Group 1		Group 2		Group 3		Group 4		Group 5
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/62 (16.1%)		6/46 (13%)		10/70 (14.3%)		4/55 (7.3%)		9/24 (37.5%)
Blood and lymphatic system disorders
Thrombocytopenia	4/62 (6.5%)	5	3/46 (6.5%)	3	4/70 (5.7%)	4	0/55 (0%)	0	1/24 (4.2%)	1
Anaemia	3/62 (4.8%)	7	0/46 (0%)	0	1/70 (1.4%)	1	3/55 (5.5%)	3	0/24 (0%)	0
Hepatobiliary disorders
Jaundice cholestatic	1/62 (1.6%)	1	0/46 (0%)	0	4/70 (5.7%)	4	0/55 (0%)	0	0/24 (0%)	0
Nervous system disorders
Intraventricular haemorrhage neonatal	0/62 (0%)	0	2/46 (4.3%)	2	0/70 (0%)	0	0/55 (0%)	0	2/24 (8.3%)	2
Psychiatric disorders
Agitation	0/62 (0%)	0	0/46 (0%)	0	0/70 (0%)	0	0/55 (0%)	0	2/24 (8.3%)	2
Respiratory, thoracic and mediastinal disorders
Respiratory failure	0/62 (0%)	0	1/46 (2.2%)	1	1/70 (1.4%)	1	1/55 (1.8%)	1	2/24 (8.3%)	2
Skin and subcutaneous tissue disorders
Skin disorder	2/62 (3.2%)	2	0/46 (0%)	0	0/70 (0%)	0	0/55 (0%)	0	2/24 (8.3%)	2

Limitations/Caveats

[Not Specified]

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.