Trial Outcomes & Findings for A Safety and Tolerability Study of Doripenem Compared With Meropenem in Children Hospitalized With Complicated Intra-abdominal Infections (NCT NCT01110382)
NCT ID: NCT01110382
Last Updated: 2014-07-15
Results Overview
The participants were considered as clinical cure if they had clinical improvement in signs and symptoms of the intra-abdominal infection such that no additional antibacterial therapy or surgical or percutaneous intervention is/was required for the treatment of the index infection, no fever, and a favorable response at End of IV visit.
TERMINATED
PHASE3
41 participants
TOC (7 to 14 days after the last dose of study medication therapy)
2014-07-15
Participant Flow
Participant milestones
| Measure |
Doripenem
Doripenem 20 mg/kg per dose (up to 500 mg/dose) was administered every 8 hours as 60-minutes IV (at least 3 days of IV doripenem only or IV doripenem followed by oral amoxicillin/clavulanate potassium). Total duration of treatment 5 to 14 days.
|
Meropenem
Meropenem 20 mg/kg per dose (up to 1 g/dose) was administered every 8 hours as 30-minutes IV (at least 3 days of IV meropenem only or IV meropenem followed by oral amoxicillin/clavulanate potassium). Total duration of treatment 5 to 14 days.
|
|---|---|---|
|
Overall Study
STARTED
|
31
|
10
|
|
Overall Study
COMPLETED
|
31
|
8
|
|
Overall Study
NOT COMPLETED
|
0
|
2
|
Reasons for withdrawal
| Measure |
Doripenem
Doripenem 20 mg/kg per dose (up to 500 mg/dose) was administered every 8 hours as 60-minutes IV (at least 3 days of IV doripenem only or IV doripenem followed by oral amoxicillin/clavulanate potassium). Total duration of treatment 5 to 14 days.
|
Meropenem
Meropenem 20 mg/kg per dose (up to 1 g/dose) was administered every 8 hours as 30-minutes IV (at least 3 days of IV meropenem only or IV meropenem followed by oral amoxicillin/clavulanate potassium). Total duration of treatment 5 to 14 days.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
|
Overall Study
Protocol Violation
|
0
|
1
|
Baseline Characteristics
A Safety and Tolerability Study of Doripenem Compared With Meropenem in Children Hospitalized With Complicated Intra-abdominal Infections
Baseline characteristics by cohort
| Measure |
Doripenem
n=31 Participants
Doripenem 20 mg/kg per dose (up to 500 mg/dose) was administered every 8 hours as 60-minutes IV (at least 3 days of IV doripenem only or IV doripenem followed by oral amoxicillin/clavulanate potassium). Total duration of treatment 5 to 14 days.
|
Meropenem
n=10 Participants
Meropenem 20 mg/kg per dose (up to 1 g/dose) was administered every 8 hours as 30-minutes IV (at least 3 days of IV meropenem only or IV meropenem followed by oral amoxicillin/clavulanate potassium). Total duration of treatment 5 to 14 days.
|
Total
n=41 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
31 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
41 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
|
8.5 years
STANDARD_DEVIATION 3.40 • n=5 Participants
|
9.3 years
STANDARD_DEVIATION 4.52 • n=7 Participants
|
8.7 years
STANDARD_DEVIATION 3.66 • n=5 Participants
|
|
Age, Customized
3 months to <2 years
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
|
Age, Customized
2 to <6 years
|
5 participants
n=5 Participants
|
3 participants
n=7 Participants
|
8 participants
n=5 Participants
|
|
Age, Customized
6 to <12 years
|
18 participants
n=5 Participants
|
4 participants
n=7 Participants
|
22 participants
n=5 Participants
|
|
Age, Customized
12 to <18 years
|
8 participants
n=5 Participants
|
3 participants
n=7 Participants
|
11 participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: TOC (7 to 14 days after the last dose of study medication therapy)Population: Clinical Intent-to-Treat (CITT): All randomized participants who met the minimal disease definition of complicated intra-abdominal infection regardless if a baseline pathogen was isolated from the intra-abdominal cavity.
The participants were considered as clinical cure if they had clinical improvement in signs and symptoms of the intra-abdominal infection such that no additional antibacterial therapy or surgical or percutaneous intervention is/was required for the treatment of the index infection, no fever, and a favorable response at End of IV visit.
Outcome measures
| Measure |
Doripenem
n=31 Participants
Doripenem 20 mg/kg per dose (up to 500 mg/dose) was administered every 8 hours as 60-minutes IV (at least 3 days of IV doripenem only or IV doripenem followed by oral amoxicillin/clavulanate potassium). Total duration of treatment 5 to 14 days.
|
Meropenem
n=10 Participants
Meropenem 20 mg/kg per dose (up to 1 g/dose) was administered every 8 hours as 30-minutes IV (at least 3 days of IV meropenem only or IV meropenem followed by oral amoxicillin/clavulanate potassium). Total duration of treatment 5 to 14 days.
|
|---|---|---|
|
The Number of Participants With Clinical Cure Rate at Test Of Cure (TOC) Visit
|
23 participants
|
7 participants
|
SECONDARY outcome
Timeframe: EIV (within 24 hours after completion of the last dose of IV study medication therapy)Population: Clinical Intent-to-Treat (CITT): All randomized participants who met the minimal disease definition of complicated intra-abdominal infection regardless if a baseline pathogen was isolated from the intra-abdominal cavity.
The participants were considered as clinical improved if they had clinical improvement in signs and symptoms of the intra-abdominal infection, no fever, decrease in WBC, and not received any nonstudy antibiotics for the treatment of intra-abdominal infection after IV study drug therapy had begun.
Outcome measures
| Measure |
Doripenem
n=31 Participants
Doripenem 20 mg/kg per dose (up to 500 mg/dose) was administered every 8 hours as 60-minutes IV (at least 3 days of IV doripenem only or IV doripenem followed by oral amoxicillin/clavulanate potassium). Total duration of treatment 5 to 14 days.
|
Meropenem
n=10 Participants
Meropenem 20 mg/kg per dose (up to 1 g/dose) was administered every 8 hours as 30-minutes IV (at least 3 days of IV meropenem only or IV meropenem followed by oral amoxicillin/clavulanate potassium). Total duration of treatment 5 to 14 days.
|
|---|---|---|
|
The Number of Participants With Clinical Improvement Rate at End of IV (EIV) Visit
|
29 participants
|
8 participants
|
SECONDARY outcome
Timeframe: LFU (28 to 42 days after the last dose of study medication therapy)Population: Clinical Intent-to-Treat (CITT): All randomized participants who met the minimal disease definition of complicated intra-abdominal infection regardless if a baseline pathogen was isolated from the intra-abdominal cavity.
The participants were considered as clinical cure if they had clinical improvement in signs and symptoms of the intra-abdominal infection such that no additional antibacterial therapy or surgical or percutaneous intervention is/was required for the treatment of the index infection, no fever, and a favorable response at End of IV visit.
Outcome measures
| Measure |
Doripenem
n=31 Participants
Doripenem 20 mg/kg per dose (up to 500 mg/dose) was administered every 8 hours as 60-minutes IV (at least 3 days of IV doripenem only or IV doripenem followed by oral amoxicillin/clavulanate potassium). Total duration of treatment 5 to 14 days.
|
Meropenem
n=10 Participants
Meropenem 20 mg/kg per dose (up to 1 g/dose) was administered every 8 hours as 30-minutes IV (at least 3 days of IV meropenem only or IV meropenem followed by oral amoxicillin/clavulanate potassium). Total duration of treatment 5 to 14 days.
|
|---|---|---|
|
The Number of Participants With Clinical Cure Rate at Late Follow-Up (LFU) Visit
|
22 participants
|
6 participants
|
SECONDARY outcome
Timeframe: EIV (within 24 hours after completion of the last dose of IV study medication therapy), TOC (7 to 14 days after the last dose of study medication therapy), and LFU (28 to 42 days after the last dose of study medication therapy)Population: Microbiological intent-to-treat - Participants of CITT with at least 1 baseline bacterial pathogen isolated from the intra-abdominal cavity that was susceptible to both doripenem and meropenem. 8 and 2 participants from doripenem and meropenem, respectively had no susceptible intra-abdominal pathogen at baseline and were excluded from this set.
Favorable per-participant microbiological response rate was evaluated at the at End of IV (EIV) visit, Test Of Cure (TOC) visit, and Late Follow-Up (LFU) visit. The favorable per-participant microbiological response was considered when all baseline pathogens were eradicated (absence) or presumed eradicated (absence of material to culture in a participant who has a positive clinical response to treatment).
Outcome measures
| Measure |
Doripenem
n=23 Participants
Doripenem 20 mg/kg per dose (up to 500 mg/dose) was administered every 8 hours as 60-minutes IV (at least 3 days of IV doripenem only or IV doripenem followed by oral amoxicillin/clavulanate potassium). Total duration of treatment 5 to 14 days.
|
Meropenem
n=8 Participants
Meropenem 20 mg/kg per dose (up to 1 g/dose) was administered every 8 hours as 30-minutes IV (at least 3 days of IV meropenem only or IV meropenem followed by oral amoxicillin/clavulanate potassium). Total duration of treatment 5 to 14 days.
|
|---|---|---|
|
The Number of Participants With Favorable Per-participant Microbiological Response
EIV visit
|
21 participants
|
6 participants
|
|
The Number of Participants With Favorable Per-participant Microbiological Response
TOC visit
|
17 participants
|
5 participants
|
|
The Number of Participants With Favorable Per-participant Microbiological Response
LFU visit
|
17 participants
|
5 participants
|
SECONDARY outcome
Timeframe: EIV (within 24 hours after completion of the last dose of IV study medication therapy)Population: Microbiological intent-to-treat - Participants of CITT with at least 1 baseline bacterial pathogen isolated from the intra-abdominal cavity that was susceptible to both doripenem and meropenem. 8 and 2 participants from doripenem and meropenem, respectively had no susceptible intra-abdominal pathogen at baseline and were excluded from this set.
A total of 24 pathogens in the doripenem group and 6 pathogens in the meropenem group were isolated at baseline from the intra-abdominal culture and were susceptible to the study drug received. The most common pathogens isolated from the intra-abdominal culture are listed in the table below; the numbers in parenthesis next to each pathogen represent the number of participants with the pathogen isolated at baseline in the doripenem and meropenem treatment groups, respectively. The favorable per-pathogen microbiological outcome was considered when all baseline pathogens were eradicated (absence) or presumed eradicated (absence of material to culture in a participant who has a positive clinical response to treatment).
Outcome measures
| Measure |
Doripenem
n=23 Participants
Doripenem 20 mg/kg per dose (up to 500 mg/dose) was administered every 8 hours as 60-minutes IV (at least 3 days of IV doripenem only or IV doripenem followed by oral amoxicillin/clavulanate potassium). Total duration of treatment 5 to 14 days.
|
Meropenem
n=8 Participants
Meropenem 20 mg/kg per dose (up to 1 g/dose) was administered every 8 hours as 30-minutes IV (at least 3 days of IV meropenem only or IV meropenem followed by oral amoxicillin/clavulanate potassium). Total duration of treatment 5 to 14 days.
|
|---|---|---|
|
Number of Participants With Favorable Per-pathogen Microbiological Outcome Rate at End of IV (EIV) Visit
Streptococcus anginosus (13, 0)
|
12 participants
|
NA participants
No isolates of Streptococcus anginosus observed at baseline.
|
|
Number of Participants With Favorable Per-pathogen Microbiological Outcome Rate at End of IV (EIV) Visit
Escherichia coli (19, 8)
|
18 participants
|
6 participants
|
|
Number of Participants With Favorable Per-pathogen Microbiological Outcome Rate at End of IV (EIV) Visit
Bacteroides fragilis (11, 1)
|
10 participants
|
1 participants
|
SECONDARY outcome
Timeframe: TOC (7 to 14 days after the last dose of study medication therapy)Population: Microbiological intent-to-treat - Participants of CITT with at least 1 baseline bacterial pathogen isolated from the intra-abdominal cavity that was susceptible to both doripenem and meropenem. 8 and 2 participants from doripenem and meropenem, respectively had no susceptible intra-abdominal pathogen at baseline and were excluded from this set.
A total of 24 pathogens in the doripenem group and 6 pathogens in the meropenem group were isolated at baseline from the intra-abdominal culture and were susceptible to the study drug received. The most common pathogens isolated from the intra-abdominal culture are listed in the table below; the numbers in parenthesis next to each pathogen represent the number of participants with the pathogen isolated at baseline in the doripenem and meropenem treatment groups, respectively. The favorable per-pathogen microbiological outcome was considered when all baseline pathogens were eradicated (absence) or presumed eradicated (absence of material to culture in a participant who has a positive clinical response to treatment).
Outcome measures
| Measure |
Doripenem
n=23 Participants
Doripenem 20 mg/kg per dose (up to 500 mg/dose) was administered every 8 hours as 60-minutes IV (at least 3 days of IV doripenem only or IV doripenem followed by oral amoxicillin/clavulanate potassium). Total duration of treatment 5 to 14 days.
|
Meropenem
n=8 Participants
Meropenem 20 mg/kg per dose (up to 1 g/dose) was administered every 8 hours as 30-minutes IV (at least 3 days of IV meropenem only or IV meropenem followed by oral amoxicillin/clavulanate potassium). Total duration of treatment 5 to 14 days.
|
|---|---|---|
|
Number of Participants With Favorable Per-pathogen Microbiological Outcome Rate at Test Of Cure (TOC) Visit
Streptococcus anginosus (13, 0)
|
9 participants
|
NA participants
No isolates of Streptococcus anginosus observed at baseline.
|
|
Number of Participants With Favorable Per-pathogen Microbiological Outcome Rate at Test Of Cure (TOC) Visit
Escherichia coli (19, 8)
|
15 participants
|
5 participants
|
|
Number of Participants With Favorable Per-pathogen Microbiological Outcome Rate at Test Of Cure (TOC) Visit
Bacteroides fragilis (11, 1)
|
9 participants
|
1 participants
|
SECONDARY outcome
Timeframe: LFU (28 to 42 days after the last dose of study medication therapy)Population: Microbiological intent-to-treat - Participants of CITT with at least 1 baseline bacterial pathogen isolated from the intra-abdominal cavity that was susceptible to both doripenem and meropenem. 8 and 2 participants from doripenem and meropenem, respectively had no susceptible intra-abdominal pathogen at baseline and were excluded from this set.
A total of 24 pathogens in the doripenem group and 6 pathogens in the meropenem group were isolated at baseline from the intra-abdominal culture and were susceptible to the study drug received. The most common pathogens isolated at baseline from the intra-abdominal culture are listed in the table below; the numbers in parenthesis next to each pathogen represent the number of participants with the pathogen isolated in the doripenem and meropenem treatment groups, respectively. The favorable per-pathogen microbiological outcome was considered when all baseline pathogens were eradicated (absence) or presumed eradicated (absence of material to culture in a participant who has a positive clinical response to treatment).
Outcome measures
| Measure |
Doripenem
n=23 Participants
Doripenem 20 mg/kg per dose (up to 500 mg/dose) was administered every 8 hours as 60-minutes IV (at least 3 days of IV doripenem only or IV doripenem followed by oral amoxicillin/clavulanate potassium). Total duration of treatment 5 to 14 days.
|
Meropenem
n=8 Participants
Meropenem 20 mg/kg per dose (up to 1 g/dose) was administered every 8 hours as 30-minutes IV (at least 3 days of IV meropenem only or IV meropenem followed by oral amoxicillin/clavulanate potassium). Total duration of treatment 5 to 14 days.
|
|---|---|---|
|
Number of Participants With Favorable Per-pathogen Microbiological Outcome Rate at Late Follow-Up (LFU) Visit
Streptococcus anginosus (13, 0)
|
9 participants
|
NA participants
No isolates of Streptococcus anginosus observed at baseline.
|
|
Number of Participants With Favorable Per-pathogen Microbiological Outcome Rate at Late Follow-Up (LFU) Visit
Escherichia coli (19, 8)
|
15 participants
|
5 participants
|
|
Number of Participants With Favorable Per-pathogen Microbiological Outcome Rate at Late Follow-Up (LFU) Visit
Bacteroides fragilis (11, 1)
|
9 participants
|
1 participants
|
Adverse Events
Doripenem
Meropenem
Serious adverse events
| Measure |
Doripenem
n=31 participants at risk
Doripenem 20 mg/kg per dose (up to 500 mg/dose) was administered every 8 hours as 60-minutes IV (at least 3 days of IV doripenem only or IV doripenem followed by oral amoxicillin/clavulanate potassium). Total duration of treatment 5 to 14 days.
|
Meropenem
n=10 participants at risk
Meropenem 20 mg/kg per dose (up to 1 g/dose) was administered every 8 hours as 30-minutes IV (at least 3 days of IV meropenem only or IV meropenem followed by oral amoxicillin/clavulanate potassium). Total duration of treatment 5 to 14 days.
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal Pain
|
9.7%
3/31 • Approximately 8 weeks
|
0.00%
0/10 • Approximately 8 weeks
|
|
Gastrointestinal disorders
Functional Gastrointestinal Disorder
|
3.2%
1/31 • Approximately 8 weeks
|
0.00%
0/10 • Approximately 8 weeks
|
|
Injury, poisoning and procedural complications
Overdose
|
3.2%
1/31 • Approximately 8 weeks
|
0.00%
0/10 • Approximately 8 weeks
|
|
Injury, poisoning and procedural complications
Seroma
|
3.2%
1/31 • Approximately 8 weeks
|
0.00%
0/10 • Approximately 8 weeks
|
|
Infections and infestations
Abdominal Abscess
|
3.2%
1/31 • Approximately 8 weeks
|
0.00%
0/10 • Approximately 8 weeks
|
Other adverse events
| Measure |
Doripenem
n=31 participants at risk
Doripenem 20 mg/kg per dose (up to 500 mg/dose) was administered every 8 hours as 60-minutes IV (at least 3 days of IV doripenem only or IV doripenem followed by oral amoxicillin/clavulanate potassium). Total duration of treatment 5 to 14 days.
|
Meropenem
n=10 participants at risk
Meropenem 20 mg/kg per dose (up to 1 g/dose) was administered every 8 hours as 30-minutes IV (at least 3 days of IV meropenem only or IV meropenem followed by oral amoxicillin/clavulanate potassium). Total duration of treatment 5 to 14 days.
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
9.7%
3/31 • Approximately 8 weeks
|
0.00%
0/10 • Approximately 8 weeks
|
|
Gastrointestinal disorders
Abdominal Distension
|
6.5%
2/31 • Approximately 8 weeks
|
10.0%
1/10 • Approximately 8 weeks
|
|
Gastrointestinal disorders
Abdominal Pain
|
6.5%
2/31 • Approximately 8 weeks
|
0.00%
0/10 • Approximately 8 weeks
|
|
Gastrointestinal disorders
Constipation
|
6.5%
2/31 • Approximately 8 weeks
|
0.00%
0/10 • Approximately 8 weeks
|
|
Gastrointestinal disorders
Vomiting
|
6.5%
2/31 • Approximately 8 weeks
|
20.0%
2/10 • Approximately 8 weeks
|
|
Gastrointestinal disorders
Diarrhoea
|
3.2%
1/31 • Approximately 8 weeks
|
20.0%
2/10 • Approximately 8 weeks
|
|
Gastrointestinal disorders
Tongue Ulceration
|
0.00%
0/31 • Approximately 8 weeks
|
10.0%
1/10 • Approximately 8 weeks
|
|
Investigations
Alanine Aminotransferase Increased
|
6.5%
2/31 • Approximately 8 weeks
|
0.00%
0/10 • Approximately 8 weeks
|
|
Investigations
Gamma-Glutamyltransferase Increased
|
6.5%
2/31 • Approximately 8 weeks
|
0.00%
0/10 • Approximately 8 weeks
|
|
Investigations
Electrocardiogram QT Prolonged
|
0.00%
0/31 • Approximately 8 weeks
|
10.0%
1/10 • Approximately 8 weeks
|
|
Blood and lymphatic system disorders
Eosinophilia
|
6.5%
2/31 • Approximately 8 weeks
|
0.00%
0/10 • Approximately 8 weeks
|
|
Cardiac disorders
Ventricular Extrasystoles
|
0.00%
0/31 • Approximately 8 weeks
|
10.0%
1/10 • Approximately 8 weeks
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/31 • Approximately 8 weeks
|
10.0%
1/10 • Approximately 8 weeks
|
|
Infections and infestations
Otitis Media
|
0.00%
0/31 • Approximately 8 weeks
|
10.0%
1/10 • Approximately 8 weeks
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/31 • Approximately 8 weeks
|
10.0%
1/10 • Approximately 8 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60