Trial Outcomes & Findings for A Safety and Tolerability Study of Doripenem Compared With Cefepime in Hospitalized Children With Bacterial Pneumonia (NCT NCT01110421)
NCT ID: NCT01110421
Last Updated: 2014-07-15
Results Overview
The participants were classified as cure if they had resolution or clinical improvement of signs and symptoms of pneumonia, favorable response at End of treatment for IV study (EIV) visit; had no fever; improvement or no progression of radiographic findings of pneumonia on chest X ray; improvement in oxygenation or discontinued mechanical ventilation in intubated participants; and not received nonstudy systemic antibacterial therapy for pneumonia.
TERMINATED
PHASE3
7 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 or ciprofloxacin). Total duration of treatment 10 to 14 days.
|
Cefepime
Cefepime 50 mg/kg per dose (up to 2 g/dose) was administered every 8 hours as 30-minutes IV (at least 3 days of IV cefepime only or IV cefepime followed by oral amoxicillin/clavulanate potassium or ciprofloxacin). Total duration of treatment 10 to 14 days.
|
|---|---|---|
|
Overall Study
STARTED
|
5
|
2
|
|
Overall Study
COMPLETED
|
5
|
2
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Safety and Tolerability Study of Doripenem Compared With Cefepime in Hospitalized Children With Bacterial Pneumonia
Baseline characteristics by cohort
| Measure |
Doripenem
n=5 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 or ciprofloxacin). Total duration of treatment 10 to 14 days.
|
Cefepime
n=2 Participants
Cefepime 50 mg/kg per dose (up to 2 g/dose) was administered every 8 hours as 30-minutes IV (at least 3 days of IV cefepime only or IV cefepime followed by oral amoxicillin/clavulanate potassium or ciprofloxacin). Total duration of treatment 10 to 14 days.
|
Total
n=7 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
5 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
7 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
|
5.2 years
STANDARD_DEVIATION 2.49 • n=5 Participants
|
4.5 years
STANDARD_DEVIATION 0.71 • n=7 Participants
|
5 years
STANDARD_DEVIATION 2.08 • 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
|
3 participants
n=5 Participants
|
2 participants
n=7 Participants
|
5 participants
n=5 Participants
|
|
Age, Customized
6 to <12 years
|
2 participants
n=5 Participants
|
0 participants
n=7 Participants
|
2 participants
n=5 Participants
|
|
Age, Customized
12 to <18 years
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
6 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 pneumonia regardless if a baseline pathogen was isolated from the baseline lower respiratory tract culture, pleural fluid or blood culture.
The participants were classified as cure if they had resolution or clinical improvement of signs and symptoms of pneumonia, favorable response at End of treatment for IV study (EIV) visit; had no fever; improvement or no progression of radiographic findings of pneumonia on chest X ray; improvement in oxygenation or discontinued mechanical ventilation in intubated participants; and not received nonstudy systemic antibacterial therapy for pneumonia.
Outcome measures
| Measure |
Doripenem
n=5 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 or ciprofloxacin). Total duration of treatment 10 to 14 days.
|
Cefepime
n=2 Participants
Cefepime 50 mg/kg per dose (up to 2 g/dose) was administered every 8 hours as 30-minutes IV (at least 3 days of IV cefepime only or IV cefepime followed by oral amoxicillin/clavulanate potassium or ciprofloxacin). Total duration of treatment 10 to 14 days.
|
|---|---|---|
|
The Number of Participants With Clinical Cure Rate at Test Of Cure (TOC) Visit
|
3 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: EIV (within 24 hours after completion of the last dose of IV study medication therapy)Population: Clinical intent-to-treat: All randomized participants who met the minimal disease definition of pneumonia regardless if a baseline pathogen was isolated from the baseline lower respiratory tract culture, pleural fluid or blood culture.
Participants were considered as clinical improved if they had no fever, clinical improvement in signs and symptoms of pneumonia from baseline, decrease in WBC, improvement or lack of progression of radiographic findings in comparison with the screening chest X-ray, and not received any nonstudy systemic antibacterial therapy for the treatment of pneumonia after IV study drug therapy had begun.
Outcome measures
| Measure |
Doripenem
n=5 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 or ciprofloxacin). Total duration of treatment 10 to 14 days.
|
Cefepime
n=2 Participants
Cefepime 50 mg/kg per dose (up to 2 g/dose) was administered every 8 hours as 30-minutes IV (at least 3 days of IV cefepime only or IV cefepime followed by oral amoxicillin/clavulanate potassium or ciprofloxacin). Total duration of treatment 10 to 14 days.
|
|---|---|---|
|
The Number of Participants With Clinical Improvement Rate at End of IV (EIV) Visit
|
4 Participants
|
2 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 pneumonia regardless if a baseline pathogen was isolated from the baseline lower respiratory tract (LRT) culture, pleural fluid or blood culture.
The participants were classified as clinical cure if all pretreatment signs and symptoms showed no evidence of resurgence after administration of the last dose of study medication and no nonstudy systemic antibacterial therapy was given for the treatment of pneumonia.
Outcome measures
| Measure |
Doripenem
n=5 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 or ciprofloxacin). Total duration of treatment 10 to 14 days.
|
Cefepime
n=2 Participants
Cefepime 50 mg/kg per dose (up to 2 g/dose) was administered every 8 hours as 30-minutes IV (at least 3 days of IV cefepime only or IV cefepime followed by oral amoxicillin/clavulanate potassium or ciprofloxacin). Total duration of treatment 10 to 14 days.
|
|---|---|---|
|
The Number of Participants With Clinical Cure Rate at Late Follow-Up (LFU) Visit
|
3 Participants
|
2 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 one baseline pneumonia pathogen from pleural fluid, LRT, or blood culture susceptible to doripenem and cefepime. 3 and 2 participants from doripenem and cefepime, respectively had no susceptible pneumonia pathogens 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=2 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 or ciprofloxacin). Total duration of treatment 10 to 14 days.
|
Cefepime
Cefepime 50 mg/kg per dose (up to 2 g/dose) was administered every 8 hours as 30-minutes IV (at least 3 days of IV cefepime only or IV cefepime followed by oral amoxicillin/clavulanate potassium or ciprofloxacin). Total duration of treatment 10 to 14 days.
|
|---|---|---|
|
The Number of Participants With Favorable Per-participant Microbiological Response Rate
TOC visit
|
2 Participants
|
—
|
|
The Number of Participants With Favorable Per-participant Microbiological Response Rate
EIV visit
|
2 Participants
|
—
|
|
The Number of Participants With Favorable Per-participant Microbiological Response Rate
LFU visit
|
2 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 one baseline pneumonia pathogen from pleural fluid, LRT, or blood culture susceptible to doripenem and cefepime. 3 and 2 participants from doripenem and cefepime, respectively had no susceptible pneumonia pathogens at baseline and were excluded from this set.
A total of 3 pathogens were isolated at baseline from lower respiratory tract (LRT) culture in 2 participants in the doripenem treatment group and were susceptible to the study drug received: 2 pathogens (Staphylococcus aureus Klebsiella pneumoniae) were isolated at baseline from 1 participant and a 3rd pathogen (Streptococcus pneumoniae) was isolated at baseline from the other participant (see listed in the table below; the number in parenthesis next to each pathogen represent the number of participants with the pathogen isolated at baseline in the doripenem treatment group). 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). NOTE: No participants in the cefepime treatment group met criteria for inclusion in the Microbiological intent-to-treat analysis.
Outcome measures
| Measure |
Doripenem
n=2 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 or ciprofloxacin). Total duration of treatment 10 to 14 days.
|
Cefepime
Cefepime 50 mg/kg per dose (up to 2 g/dose) was administered every 8 hours as 30-minutes IV (at least 3 days of IV cefepime only or IV cefepime followed by oral amoxicillin/clavulanate potassium or ciprofloxacin). Total duration of treatment 10 to 14 days.
|
|---|---|---|
|
Number of Participants With Favorable Per-pathogen Microbiological Outcome Rate at End of IV (EIV) Visit
Staphylococcus aureus (1)
|
1 Participants
|
—
|
|
Number of Participants With Favorable Per-pathogen Microbiological Outcome Rate at End of IV (EIV) Visit
Streptococcus pneumoniae (1)
|
1 Participants
|
—
|
|
Number of Participants With Favorable Per-pathogen Microbiological Outcome Rate at End of IV (EIV) Visit
Klebsiella pneumoniae (1)
|
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 one baseline pneumonia pathogen from pleural fluid, LRT, or blood culture susceptible to doripenem and cefepime. 3 and 2 participants from doripenem and cefepime, respectively had no susceptible pneumonia pathogens at baseline and were excluded from this set.
A total of 3 pathogens were isolated at baseline from lower respiratory tract (LRT) culture in 2 participants in the doripenem treatment group and were susceptible to the study drug received: 2 pathogens (Staphylococcus aureus Klebsiella pneumoniae) were isolated at baseline from 1 participant and a 3rd pathogen (Streptococcus pneumoniae) was isolated at baseline from the other participant (see listed in the table below; the number in parenthesis next to each pathogen represent the number of participants with the pathogen isolated at baseline in the doripenem treatment group). 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). NOTE: No participants in the cefepime treatment group met criteria for inclusion in the Microbiological intent-to-treat analysis.
Outcome measures
| Measure |
Doripenem
n=2 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 or ciprofloxacin). Total duration of treatment 10 to 14 days.
|
Cefepime
Cefepime 50 mg/kg per dose (up to 2 g/dose) was administered every 8 hours as 30-minutes IV (at least 3 days of IV cefepime only or IV cefepime followed by oral amoxicillin/clavulanate potassium or ciprofloxacin). Total duration of treatment 10 to 14 days.
|
|---|---|---|
|
Number of Participants With Favorable Per-pathogen Microbiological Outcome Rate at Test Of Cure (TOC) Visit
Klebsiella pneumoniae (1)
|
1 Participants
|
—
|
|
Number of Participants With Favorable Per-pathogen Microbiological Outcome Rate at Test Of Cure (TOC) Visit
Staphylococcus aureus (1)
|
1 Participants
|
—
|
|
Number of Participants With Favorable Per-pathogen Microbiological Outcome Rate at Test Of Cure (TOC) Visit
Streptococcus pneumoniae (1)
|
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 one baseline pneumonia pathogen from pleural fluid, LRT, or blood culture susceptible to doripenem and cefepime. 3 and 2 participants from doripenem and cefepime, respectively had no susceptible pneumonia pathogens at baseline and were excluded from this set.
A total of 3 pathogens were isolated at baseline from lower respiratory tract (LRT) culture in 2 participants in the doripenem treatment group and were susceptible to the study drug received: 2 pathogens (Staphylococcus aureus Klebsiella pneumoniae) were isolated at baseline from 1 participant and a 3rd pathogen (Streptococcus pneumoniae) was isolated at baseline from the other participant (see listed in the table below; the number in parenthesis next to each pathogen represent the number of participants with the pathogen isolated at baseline in the doripenem treatment group). 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). NOTE: No participants in the cefepime treatment group met criteria for inclusion in the Microbiological intent-to-treat analysis.
Outcome measures
| Measure |
Doripenem
n=2 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 or ciprofloxacin). Total duration of treatment 10 to 14 days.
|
Cefepime
Cefepime 50 mg/kg per dose (up to 2 g/dose) was administered every 8 hours as 30-minutes IV (at least 3 days of IV cefepime only or IV cefepime followed by oral amoxicillin/clavulanate potassium or ciprofloxacin). Total duration of treatment 10 to 14 days.
|
|---|---|---|
|
Number of Participants With Sustained Favorable Per-pathogen Microbiological Outcome Rate at Late Follow-Up (LFU) Visit
Staphylococcus aureus (1)
|
1 Participants
|
—
|
|
Number of Participants With Sustained Favorable Per-pathogen Microbiological Outcome Rate at Late Follow-Up (LFU) Visit
Streptococcus pneumoniae (1)
|
1 Participants
|
—
|
|
Number of Participants With Sustained Favorable Per-pathogen Microbiological Outcome Rate at Late Follow-Up (LFU) Visit
Klebsiella pneumoniae (1)
|
1 Participants
|
—
|
Adverse Events
Doripenem
Cefepime
Serious adverse events
| Measure |
Doripenem
n=5 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 or ciprofloxacin). Total duration of treatment 10 to 14 days.
|
Cefepime
n=2 participants at risk
Cefepime 50 mg/kg per dose (up to 2 g/dose) was administered every 8 hours as 30-minutes IV (at least 3 days of IV cefepime only or IV cefepime followed by oral amoxicillin/clavulanate potassium or ciprofloxacin). Total duration of treatment 10 to 14 days.
|
|---|---|---|
|
Infections and infestations
Empyema
|
20.0%
1/5 • Approximately 8 weeks
|
0.00%
0/2 • Approximately 8 weeks
|
|
Infections and infestations
Pneumonia
|
20.0%
1/5 • Approximately 8 weeks
|
0.00%
0/2 • Approximately 8 weeks
|
Other adverse events
| Measure |
Doripenem
n=5 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 or ciprofloxacin). Total duration of treatment 10 to 14 days.
|
Cefepime
n=2 participants at risk
Cefepime 50 mg/kg per dose (up to 2 g/dose) was administered every 8 hours as 30-minutes IV (at least 3 days of IV cefepime only or IV cefepime followed by oral amoxicillin/clavulanate potassium or ciprofloxacin). Total duration of treatment 10 to 14 days.
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal Pain
|
20.0%
1/5 • Approximately 8 weeks
|
0.00%
0/2 • Approximately 8 weeks
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
20.0%
1/5 • Approximately 8 weeks
|
0.00%
0/2 • Approximately 8 weeks
|
|
Gastrointestinal disorders
Diarrhoea
|
20.0%
1/5 • Approximately 8 weeks
|
0.00%
0/2 • Approximately 8 weeks
|
|
General disorders
Chest Pain
|
20.0%
1/5 • Approximately 8 weeks
|
0.00%
0/2 • Approximately 8 weeks
|
|
Immune system disorders
Hypersensitivity
|
20.0%
1/5 • Approximately 8 weeks
|
0.00%
0/2 • Approximately 8 weeks
|
|
Infections and infestations
Gastroenteritis
|
20.0%
1/5 • Approximately 8 weeks
|
0.00%
0/2 • Approximately 8 weeks
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/5 • Approximately 8 weeks
|
50.0%
1/2 • Approximately 8 weeks
|
|
Injury, poisoning and procedural complications
Stab Wound
|
20.0%
1/5 • Approximately 8 weeks
|
0.00%
0/2 • Approximately 8 weeks
|
|
Investigations
Oxygen Saturation Decreased
|
20.0%
1/5 • Approximately 8 weeks
|
0.00%
0/2 • Approximately 8 weeks
|
|
Musculoskeletal and connective tissue disorders
Flank Pain
|
20.0%
1/5 • Approximately 8 weeks
|
0.00%
0/2 • Approximately 8 weeks
|
|
Renal and urinary disorders
Dysuria
|
20.0%
1/5 • Approximately 8 weeks
|
0.00%
0/2 • Approximately 8 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Distress Syndrome
|
20.0%
1/5 • Approximately 8 weeks
|
0.00%
0/2 • Approximately 8 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Nasal Congestion
|
20.0%
1/5 • Approximately 8 weeks
|
0.00%
0/2 • Approximately 8 weeks
|
|
Skin and subcutaneous tissue disorders
Ecchymosis
|
20.0%
1/5 • Approximately 8 weeks
|
0.00%
0/2 • Approximately 8 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60