Antibiotic Safety (SCAMP) (SCAMP)

Antibiotic Safety in Infants With Complicated Intra-Abdominal Infections (SCAMP Trial)

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

Study Overview

• Status: Completed
• Conditions: Complicated Intra Abdominal Infections
• Intervention / Treatment: 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

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 Type: Interventional
• Enrollment (Actual): 260
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 3 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / 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)

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Therapeutic Success at Day 30	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	30 days after last dose of study drug

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Feeding Intolerance	Feeding intolerance confirmed by documentation of any feedings held for >24 consecutive hours in infants being fed	90 days after last dose of study drug
Number of Participants With Grade 3 and/or Grade 4 Intraventricular Hemorrhage (IVH)	Grade 3 IVH: Subependymal hemorrhage with extension into lateral ventricles with ventricular enlargement Grade 4 IVH: Intraparenchymal hemorrhage	90 days after last dose of study drug
Number of Participants With Short Bowel Syndrome	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	90 days after last dose of study drug
Number of Participants With Intestinal Perforation	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	90 days after last dose of study drug
Number of Participants With Intestinal Stricture	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	90 days after last dose of study drug
Number of Participants Progressed to a Higher Stage of Necrotizing Enterocolitis (NEC), if NEC is the Cause of the Complicated Intra-abdominal Infection	Progression is determined by the clinical NEC scoring	90 days after last dose of study drug
Number of Participants With Gastrointestinal Surgeries	Determined by medical history and confirmed with hospital records. (Laparotomy)	90 days after last dose of study drug
Number of Participants With Seizure	documented seizure(s) in hospital records	90 days after last dose of study drug
Number of Participants With Positive Blood Cultures	Positive blood culture (bacterial or fungal)	90 days after last dose of study drug

Collaborators and Investigators

• Sponsor: Michael Cohen-Wolkowiez
• Collaborators: The Emmes Company, LLC
• Investigators: Principal Investigator: Micheal Cohen-Wolkowiez, MD, PhD, Duke University

Publications and helpful links

General Publications

• Smith MJ, Boutzoukas A, Autmizguine J, Hudak ML, Zinkhan E, Bloom BT, Heresi G, Lavery AP, Courtney SE, Sokol GM, Cotten CM, Bliss JM, Mendley S, Bendel C, Dammann CEL, Weitkamp JH, Saxonhouse MA, Mundakel GT, Debski J, Sharma G, Erinjeri J, Gao J, Benjamin DK Jr, Hornik CP, Smith PB, Cohen-Wolkowiez M; Best Pharmaceuticals for Children Act-Pediatric Trials Network Steering Committee. Antibiotic Safety and Effectiveness in Premature Infants With Complicated Intraabdominal Infections. Pediatr Infect Dis J. 2021 Jun 1;40(6):550-555. doi: 10.1097/INF.0000000000003034.

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Actual): January 15, 2017
• Study Completion (Actual): April 20, 2017

Study Registration Dates

• First Submitted: November 18, 2013
• First Submitted That Met QC Criteria: November 25, 2013
• First Posted (Estimate): November 26, 2013

Study Record Updates

• Last Update Posted (Actual): May 30, 2019
• Last Update Submitted That Met QC Criteria: May 28, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: Safety; Antibiotics; Infants; metronidazole; piperacillin-tazobactam; clindamycin; ampicillin; Intra abdominal infections
• Additional Relevant MeSH Terms: Infections; Intraabdominal Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Protein Synthesis Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; beta-Lactamase Inhibitors; Metronidazole; Ampicillin; Anti-Bacterial Agents; Clindamycin; Clindamycin palmitate; Clindamycin phosphate; Gentamicins; Piperacillin; Tazobactam; Piperacillin, Tazobactam Drug Combination
• Other Study ID Numbers: Pro00048773; HHSN275201000003I (Other Identifier: National Institute of Child Health & Human Development)