Antibiotic Safety (SCAMP)

Study Overview
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Brief Summary
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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

Detailed Description
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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.

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

Conditions
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Complicated Intra Abdominal Infections

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent obtained from parent(s) or legal guardian(s) (Groups 1-5) ≤33 weeks gestation at birth (Groups 1-3, 5) ≥34 weeks gestation at birth (Groups 4 and 5) PNA <121 days (Groups 1-5) Sufficient venous access to permit administration of study drug (intravenous [IV]) (Groups 1-5) 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. 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* History of anaphylaxis in response to study drugs (Groups 1-5) Serum creatinine >2 mg/dL within 48 hours on measurement prior to and closest to randomization /first study drug dose (Groups 1- 5)** 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)** 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.

Ages Eligible for Study
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Maximum Age: 120 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 1 (ampicillin +gentamycin +metronidazole)<br>Ampicillin and gentamycin and metronidazole | Drug: ampicillin and metronidazole and gentamicin<br>* IV infusion of ampicillin and metronidazole and gentamicin for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)<br>|
| Active Comparator: Group 2 (ampicillin +gentamicin+clindamycin)<br>ampicillin and gentamicin and clindamycin | Drug: ampicillin and gentamicin and clindamycin<br>* IV infusion of ampicillin and gentamicin and clindamycin for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)<br>|
| Active Comparator: Group 3 (piperacillin-tazobactam and gentamicin)<br>piperacillin-tazobactam and gentamicin | Drug: gentamicin and Piperacillin- tazobactam<br>* IV infusion of gentamicin and Piperacillin- tazobactam for a total of 10 days. Dose based on postnatal age (PNA) and gestational age(GA)<br>|
| Active Comparator: Group 4 (metronidazole)<br>Per standard of care antibiotics, and Metronidazole | Drug: standard of care antibiotics and metronidazole<br>* 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)<br>|
| Active Comparator: Group 5 (metronidazole/clindamycin/piperacillin-tazobactam)<br>metronidazole, clindamycin, or piperacillin-tazobactam | Drug: metronidazole, clindamycin, or piperacillin-tazobactam<br>* 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)<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antibiotics, ampicillin, metronidazole, clindamycin, piperacillin-tazobactam, Safety, Infants, Intra abdominal infections