Antibiotic Safety (SCAMP)

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

Status

Completed

Phases

Phase 2Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01994993

Acronym

SCAMP

Enrollment

260

Registered

2013-11-26

Start date

2013-12-31

Completion date

2017-04-20

Last updated

2019-05-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Complicated Intra Abdominal Infections

Keywords

Antibiotics, ampicillin, metronidazole, clindamycin, piperacillin-tazobactam, Safety, Infants, Intra abdominal infections

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

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.

Interventions

DRUGampicillin 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)

DRUGampicillin 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)

DRUGgentamicin 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)

DRUGstandard 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)

DRUGmetronidazole, 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)

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

No minimum to 120 Days

Healthy volunteers

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.

Design outcomes

Primary

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

Secondary

Measure	Time frame	Description
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

Measure	Time frame	Description
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
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
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
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
Number of Participants With Gastrointestinal Surgeries	90 days after last dose of study drug	Determined by medical history and confirmed with hospital records. (Laparotomy)
Number of Participants With Seizure	90 days after last dose of study drug	documented seizure(s) in hospital records
Number of Participants With Positive Blood Cultures	90 days after last dose of study drug	Positive blood culture (bacterial or fungal)
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
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

Countries

Canada, United States

Participant flow

Pre-assignment details

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

Participants by arm

Arm	Count
Group 1 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)	62
Group 2 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)	46
Group 3 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)	70
Group 4 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)	55
Group 5 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)	24
Total	257

Baseline characteristics

Characteristic	Group 1	Total	Group 5	Group 4	Group 3	Group 2
Age, Continuous	27.3 Gestational Age (weeks) STANDARD_DEVIATION 2.6	29.5 Gestational Age (weeks) STANDARD_DEVIATION 4.6	28.9 Gestational Age (weeks) STANDARD_DEVIATION 4.9	36.4 Gestational Age (weeks) STANDARD_DEVIATION 2.1	27.5 Gestational Age (weeks) STANDARD_DEVIATION 2.9	27.8 Gestational Age (weeks) STANDARD_DEVIATION 3
Ethnicity (NIH/OMB) Hispanic or Latino	12 Participants	47 Participants	1 Participants	12 Participants	11 Participants	11 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	46 Participants	190 Participants	20 Participants	38 Participants	52 Participants	34 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	4 Participants	20 Participants	3 Participants	5 Participants	7 Participants	1 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants	2 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	3 Participants	0 Participants	1 Participants	1 Participants	1 Participants
Race (NIH/OMB) Black or African American	20 Participants	67 Participants	6 Participants	8 Participants	23 Participants	10 Participants
Race (NIH/OMB) More than one race	2 Participants	10 Participants	2 Participants	1 Participants	4 Participants	1 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	7 Participants	31 Participants	2 Participants	9 Participants	5 Participants	8 Participants
Race (NIH/OMB) White	32 Participants	144 Participants	14 Participants	35 Participants	37 Participants	26 Participants
Region of Enrollment Canada	4 count of participants	5 count of participants	1 count of participants	0 count of participants	0 count of participants	0 count of participants
Region of Enrollment United States	58 count of participants	252 count of participants	23 count of participants	55 count of participants	70 count of participants	46 count of participants
Sex: Female, Male Female	18 Participants	114 Participants	10 Participants	27 Participants	42 Participants	17 Participants
Sex: Female, Male Male	44 Participants	143 Participants	14 Participants	28 Participants	28 Participants	29 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk
deaths Total, all-cause mortality	5 / 62	5 / 46	7 / 70	1 / 55	0 / 24
other Total, other adverse events	10 / 62	6 / 46	10 / 70	4 / 55	9 / 24
serious Total, serious adverse events	19 / 62	10 / 46	12 / 70	3 / 55	3 / 24

Outcome results

Primary

Death

Number of Participants who experienced Death

Time frame: Within 30 days after last dose of study drug, up to 40 days

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

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Group 1	Death	5 Participants
Group 2	Death	5 Participants
Group 3	Death	7 Participants
Group 4	Death	1 Participants
Group 5	Death	0 Participants

Secondary

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

Time frame: 30 days after last dose of study drug

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

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Group 1	Number of Participants With Therapeutic Success at Day 30	45 Participants
Group 2	Number of Participants With Therapeutic Success at Day 30	39 Participants
Group 3	Number of Participants With Therapeutic Success at Day 30	52 Participants
Group 4	Number of Participants With Therapeutic Success at Day 30	52 Participants

Other Pre-specified