Trial Outcomes & Findings for A Safety and Tolerability Study of Doripenem Compared With Cefepime in Children Hospitalized With Complicated Urinary Tract Infections (NCT NCT01110408)

NCT ID: NCT01110408

Last Updated: 2014-07-15

Results Overview

The participants were classified as cure if they had resolution or clinical improvement in signs and symptoms of complicated urinary tract infection; had no fever; no additional antimicrobial therapy was required for the treatment of the infection; and a clinical response assessment of improvement at End of IV visit.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

41 participants

Primary outcome timeframe

TOC (7 to 14 days after the last dose of study medication therapy)

Results posted on

2014-07-15

Participant Flow

Participant milestones

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
31
10
Overall Study
COMPLETED
30
10
Overall Study
NOT COMPLETED
1
0

Reasons for withdrawal

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 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
Protocol Violation
1
0

Baseline Characteristics

A Safety and Tolerability Study of Doripenem Compared With Cefepime in Children Hospitalized With Complicated Urinary Tract Infections

Baseline characteristics by cohort

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 or ciprofloxacin). Total duration of treatment 10 to 14 days.
Cefepime
n=10 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=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
4.7 years
STANDARD_DEVIATION 5.15 • n=5 Participants
4.3 years
STANDARD_DEVIATION 4.16 • n=7 Participants
4.6 years
STANDARD_DEVIATION 4.88 • n=5 Participants
Age, Customized
3 months to <2 years
12 participants
n=5 Participants
4 participants
n=7 Participants
16 participants
n=5 Participants
Age, Customized
2 to <6 years
8 participants
n=5 Participants
2 participants
n=7 Participants
10 participants
n=5 Participants
Age, Customized
6 to <12 years
7 participants
n=5 Participants
3 participants
n=7 Participants
10 participants
n=5 Participants
Age, Customized
12 to <18 years
4 participants
n=5 Participants
1 participants
n=7 Participants
5 participants
n=5 Participants
Sex: Female, Male
Female
26 Participants
n=5 Participants
5 Participants
n=7 Participants
31 Participants
n=5 Participants
Sex: Female, Male
Male
5 Participants
n=5 Participants
5 Participants
n=7 Participants
10 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 urinary tract infection regardless if a baseline pathogen was isolated from the pretreatment urine culture.

The participants were classified as cure if they had resolution or clinical improvement in signs and symptoms of complicated urinary tract infection; had no fever; no additional antimicrobial therapy was required for the treatment of the infection; and a clinical response assessment of improvement at End of IV visit.

Outcome measures

Outcome measures
Measure
Doripenem
n=30 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=10 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
20 Participants
5 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 urinary tract infection regardless if a baseline pathogen was isolated from the pretreatment urine culture.

The participants were considered as clinical improved if they had clinical improvement in signs and symptoms from baseline; no fever for at least the 24 hours before discontinuing the IV study drug; and not received nonstudy antibiotics for the treatment of urinary tract infection after IV study drug therapy had begun.

Outcome measures

Outcome measures
Measure
Doripenem
n=30 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=10 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
28 Participants
10 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 urinary tract infection regardless if a baseline pathogen was isolated from the pretreatment urine culture.

The participants were classified as clinical cure if all pretreatment signs and symptoms of complicated urinary tract infection showed no evidence of recurrence after test of cure.

Outcome measures

Outcome measures
Measure
Doripenem
n=30 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=10 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
18 Participants
5 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 all CITT with at least 1 baseline bacterial pathogen isolated from the pretreatment urine culture, susceptible to both doripenem and cefepime. 6 and 2 participants from doripenem and cefepime, respectively had no susceptible urine 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

Outcome measures
Measure
Doripenem
n=24 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=8 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 Favorable Per-participant Microbiological Response
EIV visit
24 Participants
8 Participants
The Number of Participants With Favorable Per-participant Microbiological Response
TOC visit
19 Participants
4 Participants
The Number of Participants With Favorable Per-participant Microbiological Response
LFU visit
16 Participants
4 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 all CITT with at least 1 baseline bacterial pathogen isolated from the pretreatment urine culture, susceptible to both doripenem and cefepime. 6 and 2 participants from doripenem and cefepime, respectively had no susceptible urine pathogens at baseline and were excluded from this set.

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).A total of 4 pathogens in the doripenem group and 2 pathogens in the cefepime group were isolated at baseline from urine culture and were susceptible to the study drug received (see 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 cefepime treatment groups, respectively).

Outcome measures

Outcome measures
Measure
Doripenem
n=24 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=8 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.
Number of Participants With Favorable Per-pathogen Microbiological Outcome Rate at End of IV (EIV) Visit
Staphylococcus aureus (3, 0)
3 Participants
NA Participants
There were no participants with Stapylococcus aureus isolated at baseline.
Number of Participants With Favorable Per-pathogen Microbiological Outcome Rate at End of IV (EIV) Visit
Escherichia coli (22, 7)
22 Participants
7 Participants
Number of Participants With Favorable Per-pathogen Microbiological Outcome Rate at End of IV (EIV) Visit
Klebsiella oxytoca (1, 0)
1 Participants
NA Participants
There were no participants with Klebsiella oxytoca isolated at baseline.
Number of Participants With Favorable Per-pathogen Microbiological Outcome Rate at End of IV (EIV) Visit
Klebsiella pneumoniae (1, 1)
1 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 all CITT with at least 1 baseline bacterial pathogen isolated from the pretreatment urine culture, susceptible to both doripenem and cefepime. 6 and 2 participants from doripenem and cefepime, respectively had no susceptible urine pathogens at baseline and were excluded from this set.

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). A total of 4 pathogens in the doripenem group and 2 pathogens in the cefepime group were isolated at baseline from urine culture and were susceptible to the study drug received (see 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 cefepime treatment groups, respectively).

Outcome measures

Outcome measures
Measure
Doripenem
n=24 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=8 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.
Number of Participants With Favorable Per-pathogen Microbiological Outcome Rate at Test Of Cure (TOC) Visit
Staphylococcus aureus (3, 0)
3 Participants
NA Participants
There were no participants with Stapylococcus aureus isolated at baseline.
Number of Participants With Favorable Per-pathogen Microbiological Outcome Rate at Test Of Cure (TOC) Visit
Escherichia coli (22, 7)
17 Participants
4 Participants
Number of Participants With Favorable Per-pathogen Microbiological Outcome Rate at Test Of Cure (TOC) Visit
Klebsiella oxytoca (1, 0)
1 Participants
NA Participants
There were no participants with Klebsiella oxytoca isolated at baseline
Number of Participants With Favorable Per-pathogen Microbiological Outcome Rate at Test Of Cure (TOC) Visit
Klebsiella pneumoniae (1, 1)
1 Participants
0 Participants

SECONDARY outcome

Timeframe: LFU (28 to 42 days after the last dose of study medication therapy)

Population: Microbiological intent-to-treat - Participants of all CITT with at least 1 baseline bacterial pathogen isolated from the pretreatment urine culture, susceptible to both doripenem and cefepime. 6 and 2 participants from doripenem and cefepime, respectively had no susceptible urine pathogens at baseline and were excluded from this set.

The sustained 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). A total of 4 pathogens in the doripenem group and 2 pathogens in the cefepime group were isolated at baseline from urine culture and were susceptible to the study drug received (see 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 cefepime treatment groups, respectively).

Outcome measures

Outcome measures
Measure
Doripenem
n=24 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=8 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.
Number of Participants With Sustained Favorable Per-pathogen Microbiological Outcome Rate at Late Follow-Up (LFU) Visit
Staphylococcus aureus (3, 0)
2 Participants
NA Participants
There were no participants with Stapylococcus aureus isolated at baseline.
Number of Participants With Sustained Favorable Per-pathogen Microbiological Outcome Rate at Late Follow-Up (LFU) Visit
Escherichia coli (22, 7)
14 Participants
4 Participants
Number of Participants With Sustained Favorable Per-pathogen Microbiological Outcome Rate at Late Follow-Up (LFU) Visit
Klebsiella oxytoca (1, 0)
1 Participants
NA Participants
There were no participants with Klebsiella oxytoca isolated at baseline.
Number of Participants With Sustained Favorable Per-pathogen Microbiological Outcome Rate at Late Follow-Up (LFU) Visit
Klebsiella pneumoniae (1, 1)
1 Participants
0 Participants

Adverse Events

Doripenem

Serious events: 1 serious events
Other events: 11 other events
Deaths: 0 deaths

Cefepime

Serious events: 3 serious events
Other events: 6 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Doripenem
n=30 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=10 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.
Renal and urinary disorders
Pyuria
3.3%
1/30 • Approximately 8 weeks
0.00%
0/10 • Approximately 8 weeks
Infections and infestations
Pseudomembranous Colitis
0.00%
0/30 • Approximately 8 weeks
10.0%
1/10 • Approximately 8 weeks
Infections and infestations
Pyelonephritis Acute
0.00%
0/30 • Approximately 8 weeks
10.0%
1/10 • Approximately 8 weeks
Infections and infestations
Urinary Tract Infection
0.00%
0/30 • Approximately 8 weeks
20.0%
2/10 • Approximately 8 weeks

Other adverse events

Other adverse events
Measure
Doripenem
n=30 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=10 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
Vomiting
10.0%
3/30 • Approximately 8 weeks
0.00%
0/10 • Approximately 8 weeks
Gastrointestinal disorders
Diarrhoea
6.7%
2/30 • Approximately 8 weeks
0.00%
0/10 • Approximately 8 weeks
General disorders
Pyrexia
10.0%
3/30 • Approximately 8 weeks
10.0%
1/10 • Approximately 8 weeks
General disorders
Infusion Site Pain
0.00%
0/30 • Approximately 8 weeks
10.0%
1/10 • Approximately 8 weeks
General disorders
Vessel Puncture Site Pain
0.00%
0/30 • Approximately 8 weeks
10.0%
1/10 • Approximately 8 weeks
Infections and infestations
Nasopharyngitis
10.0%
3/30 • Approximately 8 weeks
0.00%
0/10 • Approximately 8 weeks
Infections and infestations
Bacteriuria
0.00%
0/30 • Approximately 8 weeks
10.0%
1/10 • Approximately 8 weeks
Infections and infestations
Candidiasis
0.00%
0/30 • Approximately 8 weeks
10.0%
1/10 • Approximately 8 weeks
Infections and infestations
Pharyngitis
0.00%
0/30 • Approximately 8 weeks
10.0%
1/10 • Approximately 8 weeks
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
6.7%
2/30 • Approximately 8 weeks
0.00%
0/10 • Approximately 8 weeks
Respiratory, thoracic and mediastinal disorders
Productive Cough
0.00%
0/30 • Approximately 8 weeks
10.0%
1/10 • Approximately 8 weeks
Blood and lymphatic system disorders
Eosinophilia
3.3%
1/30 • Approximately 8 weeks
10.0%
1/10 • Approximately 8 weeks
Blood and lymphatic system disorders
Hypochromic Anaemia
0.00%
0/30 • Approximately 8 weeks
10.0%
1/10 • Approximately 8 weeks
Blood and lymphatic system disorders
Neutrophilia
0.00%
0/30 • Approximately 8 weeks
10.0%
1/10 • Approximately 8 weeks
Skin and subcutaneous tissue disorders
Papule
3.3%
1/30 • Approximately 8 weeks
10.0%
1/10 • Approximately 8 weeks
Skin and subcutaneous tissue disorders
Rash
0.00%
0/30 • Approximately 8 weeks
10.0%
1/10 • Approximately 8 weeks
Skin and subcutaneous tissue disorders
Skin Haemorrhage
0.00%
0/30 • Approximately 8 weeks
10.0%
1/10 • Approximately 8 weeks
Congenital, familial and genetic disorders
Congenital Thrombocyte Disorder
0.00%
0/30 • Approximately 8 weeks
10.0%
1/10 • Approximately 8 weeks
Injury, poisoning and procedural complications
Overdose
0.00%
0/30 • Approximately 8 weeks
10.0%
1/10 • Approximately 8 weeks
Investigations
Basophil Count Increased
0.00%
0/30 • Approximately 8 weeks
10.0%
1/10 • Approximately 8 weeks
Investigations
Urine Leukocyte Esterase
0.00%
0/30 • Approximately 8 weeks
10.0%
1/10 • Approximately 8 weeks
Metabolism and nutrition disorders
Hypoalbuminaemia
0.00%
0/30 • Approximately 8 weeks
10.0%
1/10 • Approximately 8 weeks
Musculoskeletal and connective tissue disorders
Myalgia
0.00%
0/30 • Approximately 8 weeks
10.0%
1/10 • Approximately 8 weeks
Renal and urinary disorders
Crystalluria
0.00%
0/30 • Approximately 8 weeks
10.0%
1/10 • Approximately 8 weeks
Renal and urinary disorders
Haematuria
0.00%
0/30 • Approximately 8 weeks
10.0%
1/10 • Approximately 8 weeks
Renal and urinary disorders
Leukocyturia
0.00%
0/30 • Approximately 8 weeks
10.0%
1/10 • Approximately 8 weeks
Renal and urinary disorders
Proteinuria
0.00%
0/30 • Approximately 8 weeks
10.0%
1/10 • Approximately 8 weeks
Vascular disorders
Phlebitis
0.00%
0/30 • Approximately 8 weeks
10.0%
1/10 • Approximately 8 weeks

Additional Information

Therapeutic Areas Director

Janssen R&D US

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place

Restriction type: GT60