Trial Outcomes & Findings for To Compare Safety and Efficacy of Doripenem Versus Imipenem-Cilastatin in Patients With Ventilator-Associated Pneumonia (NCT NCT00589693)

Last Updated: 2012-12-28

Results Overview

The number of patients who achieved clinical cure at the EOT visit on Day 10. The patient's were classified as clinical cure if they had resolution of signs and symptoms and objective findings of pneumonia to such an extent that no further antimicrobial therapy was necessary.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

274 participants

Primary outcome timeframe

End-of-treatment (Day 10 or Day 11)

Results posted on

2012-12-28

Participant Flow

274 enrolled patients were randomnly assigned to the 127 study centers. 524 patients were to be enrolled, however as the study was terminated early only 274 patients were actually enrolled.

Out of 274 randomized patients, 41 patients were excluded (as their sites were GCP Non-Compliant) and 6 patients were not treated. Treated patients=227 (115 doripenem and 112 imipenem-cilastatin).

Participant milestones

Participant milestones
Measure	Doripenem 1 g 4-hour infusion intravenously every 8 hour for 7 days	Imipenem-cilastatin 1 g 1-hour infusion intravenously every 8 hour for 10 days
Overall Study STARTED	115	112
Overall Study COMPLETED	71	83
Overall Study NOT COMPLETED	44	29

Reasons for withdrawal

Reasons for withdrawal
Measure	Doripenem 1 g 4-hour infusion intravenously every 8 hour for 7 days	Imipenem-cilastatin 1 g 1-hour infusion intravenously every 8 hour for 10 days
Overall Study randomized in error	12	6
Overall Study Adverse Event	4	4
Overall Study Death	26	16
Overall Study Lack of Efficacy	0	1
Overall Study Lost to Follow-up	1	0
Overall Study Physician Decision	0	1
Overall Study Protocol Violation	1	1

Baseline Characteristics

To Compare Safety and Efficacy of Doripenem Versus Imipenem-Cilastatin in Patients With Ventilator-Associated Pneumonia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Doripenem n=115 Participants 1 g 4-hour infusion intravenously every 8 hour for 7 days	Imipenem-cilastatin n=112 Participants 1 g 1-hour infusion intravenously every 8 hour for 10 days	Total n=227 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	72 Participants n=5 Participants	72 Participants n=7 Participants	144 Participants n=5 Participants
Age, Categorical >=65 years	43 Participants n=5 Participants	39 Participants n=7 Participants	82 Participants n=5 Participants
Age Continuous	57.5 years STANDARD_DEVIATION 16.53 • n=5 Participants	54.6 years STANDARD_DEVIATION 18.46 • n=7 Participants	56.1 years STANDARD_DEVIATION 17.53 • n=5 Participants
Sex: Female, Male Female	43 Participants n=5 Participants	37 Participants n=7 Participants	80 Participants n=5 Participants
Sex: Female, Male Male	72 Participants n=5 Participants	75 Participants n=7 Participants	147 Participants n=5 Participants
Region Enroll EUROPE	69 participants n=5 Participants	71 participants n=7 Participants	140 participants n=5 Participants
Region Enroll NORTH AMERICA	16 participants n=5 Participants	12 participants n=7 Participants	28 participants n=5 Participants
Region Enroll REST OF WORLD	9 participants n=5 Participants	6 participants n=7 Participants	15 participants n=5 Participants
Region Enroll SOUTH AMERICA	21 participants n=5 Participants	23 participants n=7 Participants	44 participants n=5 Participants

PRIMARY outcome

Timeframe: End-of-treatment (Day 10 or Day 11)

Population: Microbiological Intent-to-Treat (MITT) - subset of all ITT (all randomized patients who received at least a partial dose of study medication) patients who had at least 1 qualifying pneumonia pathogen.

Outcome measures

Outcome measures
Measure	Doripenem n=79 Participants 1 g 4-hour infusion intravenously every 8 hour for 7 days	Imipenem-cilastatin n=88 Participants 1 g 1-hour infusion intravenously every 8 hour for 10 days
Clinical Cure Rate at the End-of-treatment (EOT) Visit	36 Participants	50 Participants

SECONDARY outcome

Timeframe: End-of-treatment (Day 10 or Day 11)

The clinical cure rate at the EOT visit in patients, whose bronchoalveolar lavage (BAL) or mini-BAL culture results yielded qualifying pneumonia pathogen P. aeruginosa at baseline.

Outcome measures

Outcome measures
Measure	Doripenem n=17 Participants 1 g 4-hour infusion intravenously every 8 hour for 7 days	Imipenem-cilastatin n=10 Participants 1 g 1-hour infusion intravenously every 8 hour for 10 days
Clinical Cure Rate at the End-of-treatment (EOT) Visit in Patients From Whom a Qualifying P. Aeruginosa Was Isolated at Baseline	7 Participants	6 Participants

SECONDARY outcome

Timeframe: End-of-treatment (Day 10 or Day 11)

The clinical cure rate at the EOT visit in patients whose BAL or mini-BAL culture results yielded at least 1 of the following Gram-negative qualifying pneumonia pathogens was isolated at baseline: any Enterobacteriaceae, P. aeruginosa, and Acinetobacter Spp.

Outcome measures

Outcome measures
Measure	Doripenem n=65 Participants 1 g 4-hour infusion intravenously every 8 hour for 7 days	Imipenem-cilastatin n=62 Participants 1 g 1-hour infusion intravenously every 8 hour for 10 days
Clinical Cure Rate at the End-of-treatment (EOT) Visit in Patients From Whom at Least 1 of the Gram-negative Qualifying Pneumonia Pathogens (Enterobacteriaceae, P. Aeruginosa, and Acinetobacter Spp) Was Isolated at Baseline	32 Participants	34 Participants

SECONDARY outcome

Timeframe: Up to 6 weeks

Number of patients who had P. aeruginosa isolates with a 4 fold or greater increase in minimum inhibitory concentration (MIC) at anytime during the study (after the study medication is received) from baseline

Outcome measures

Outcome measures
Measure	Doripenem n=19 Participants 1 g 4-hour infusion intravenously every 8 hour for 7 days	Imipenem-cilastatin n=15 Participants 1 g 1-hour infusion intravenously every 8 hour for 10 days
Number of Patients Who Had Emergence of P. Aeruginosa Resistance	3 Participants	6 Participants

SECONDARY outcome

Timeframe: Up to 28 days

Number of deaths which occured up to 28 days of the study period due to all causes

Outcome measures

Outcome measures
Measure	Doripenem n=79 Participants 1 g 4-hour infusion intravenously every 8 hour for 7 days	Imipenem-cilastatin n=88 Participants 1 g 1-hour infusion intravenously every 8 hour for 10 days
28-day All-cause Mortality Rate	17 Participants	13 Participants

Adverse Events

Doripenem

Serious events: 55 serious events

Other events: 82 other events

Deaths: 0 deaths

Imipenem-cilastatin

Serious events: 45 serious events

Other events: 80 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Sr Director Clinical Development

Janssen R&D US

Phone: 1 510 248-2310

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	Doripenem n=115 participants at risk 1 g 4-hour infusion intravenously every 8 hour for 7 days	Imipenem-cilastatin n=112 participants at risk 1 g 1-hour infusion intravenously every 8 hour for 10 days
Blood and lymphatic system disorders Anaemia	22.6% 26/115 • 6 weeks Only patients who had at least one of the treatment related adverse events (AEs) was listed in the other (non Serious) AE table and was included as the total number of patients with Non-Serious Adverse Events.	22.3% 25/112 • 6 weeks Only patients who had at least one of the treatment related adverse events (AEs) was listed in the other (non Serious) AE table and was included as the total number of patients with Non-Serious Adverse Events.
Metabolism and nutrition disorders Hyperkalaemia	5.2% 6/115 • 6 weeks Only patients who had at least one of the treatment related adverse events (AEs) was listed in the other (non Serious) AE table and was included as the total number of patients with Non-Serious Adverse Events.	5.4% 6/112 • 6 weeks Only patients who had at least one of the treatment related adverse events (AEs) was listed in the other (non Serious) AE table and was included as the total number of patients with Non-Serious Adverse Events.
Metabolism and nutrition disorders Hypernatraemia	4.3% 5/115 • 6 weeks Only patients who had at least one of the treatment related adverse events (AEs) was listed in the other (non Serious) AE table and was included as the total number of patients with Non-Serious Adverse Events.	6.2% 7/112 • 6 weeks Only patients who had at least one of the treatment related adverse events (AEs) was listed in the other (non Serious) AE table and was included as the total number of patients with Non-Serious Adverse Events.
Metabolism and nutrition disorders Hyponatraemia	4.3% 5/115 • 6 weeks Only patients who had at least one of the treatment related adverse events (AEs) was listed in the other (non Serious) AE table and was included as the total number of patients with Non-Serious Adverse Events.	8.9% 10/112 • 6 weeks Only patients who had at least one of the treatment related adverse events (AEs) was listed in the other (non Serious) AE table and was included as the total number of patients with Non-Serious Adverse Events.
Metabolism and nutrition disorders Hypomagnesaemia	3.5% 4/115 • 6 weeks Only patients who had at least one of the treatment related adverse events (AEs) was listed in the other (non Serious) AE table and was included as the total number of patients with Non-Serious Adverse Events.	6.2% 7/112 • 6 weeks Only patients who had at least one of the treatment related adverse events (AEs) was listed in the other (non Serious) AE table and was included as the total number of patients with Non-Serious Adverse Events.
Infections and infestations Urinary tract infection	11.3% 13/115 • 6 weeks Only patients who had at least one of the treatment related adverse events (AEs) was listed in the other (non Serious) AE table and was included as the total number of patients with Non-Serious Adverse Events.	14.3% 16/112 • 6 weeks Only patients who had at least one of the treatment related adverse events (AEs) was listed in the other (non Serious) AE table and was included as the total number of patients with Non-Serious Adverse Events.
Infections and infestations Pneumonia	5.2% 6/115 • 6 weeks Only patients who had at least one of the treatment related adverse events (AEs) was listed in the other (non Serious) AE table and was included as the total number of patients with Non-Serious Adverse Events.	8.0% 9/112 • 6 weeks Only patients who had at least one of the treatment related adverse events (AEs) was listed in the other (non Serious) AE table and was included as the total number of patients with Non-Serious Adverse Events.
Skin and subcutaneous tissue disorders Decubitus ulcer	12.2% 14/115 • 6 weeks Only patients who had at least one of the treatment related adverse events (AEs) was listed in the other (non Serious) AE table and was included as the total number of patients with Non-Serious Adverse Events.	9.8% 11/112 • 6 weeks Only patients who had at least one of the treatment related adverse events (AEs) was listed in the other (non Serious) AE table and was included as the total number of patients with Non-Serious Adverse Events.
Vascular disorders Hypotension	9.6% 11/115 • 6 weeks Only patients who had at least one of the treatment related adverse events (AEs) was listed in the other (non Serious) AE table and was included as the total number of patients with Non-Serious Adverse Events.	7.1% 8/112 • 6 weeks Only patients who had at least one of the treatment related adverse events (AEs) was listed in the other (non Serious) AE table and was included as the total number of patients with Non-Serious Adverse Events.
Vascular disorders Hypertension	1.7% 2/115 • 6 weeks Only patients who had at least one of the treatment related adverse events (AEs) was listed in the other (non Serious) AE table and was included as the total number of patients with Non-Serious Adverse Events.	5.4% 6/112 • 6 weeks Only patients who had at least one of the treatment related adverse events (AEs) was listed in the other (non Serious) AE table and was included as the total number of patients with Non-Serious Adverse Events.
Cardiac disorders Atrial fibrillation	7.8% 9/115 • 6 weeks Only patients who had at least one of the treatment related adverse events (AEs) was listed in the other (non Serious) AE table and was included as the total number of patients with Non-Serious Adverse Events.	7.1% 8/112 • 6 weeks Only patients who had at least one of the treatment related adverse events (AEs) was listed in the other (non Serious) AE table and was included as the total number of patients with Non-Serious Adverse Events.
Cardiac disorders Bradycardia	2.6% 3/115 • 6 weeks Only patients who had at least one of the treatment related adverse events (AEs) was listed in the other (non Serious) AE table and was included as the total number of patients with Non-Serious Adverse Events.	5.4% 6/112 • 6 weeks Only patients who had at least one of the treatment related adverse events (AEs) was listed in the other (non Serious) AE table and was included as the total number of patients with Non-Serious Adverse Events.
General disorders Pyrexia	9.6% 11/115 • 6 weeks Only patients who had at least one of the treatment related adverse events (AEs) was listed in the other (non Serious) AE table and was included as the total number of patients with Non-Serious Adverse Events.	8.9% 10/112 • 6 weeks Only patients who had at least one of the treatment related adverse events (AEs) was listed in the other (non Serious) AE table and was included as the total number of patients with Non-Serious Adverse Events.
Renal and urinary disorders Renal impairment	5.2% 6/115 • 6 weeks Only patients who had at least one of the treatment related adverse events (AEs) was listed in the other (non Serious) AE table and was included as the total number of patients with Non-Serious Adverse Events.	3.6% 4/112 • 6 weeks Only patients who had at least one of the treatment related adverse events (AEs) was listed in the other (non Serious) AE table and was included as the total number of patients with Non-Serious Adverse Events.
Metabolism and nutrition disorders Hypokalaemia	10.4% 12/115 • 6 weeks Only patients who had at least one of the treatment related adverse events (AEs) was listed in the other (non Serious) AE table and was included as the total number of patients with Non-Serious Adverse Events.	10.7% 12/112 • 6 weeks Only patients who had at least one of the treatment related adverse events (AEs) was listed in the other (non Serious) AE table and was included as the total number of patients with Non-Serious Adverse Events.
Respiratory, thoracic and mediastinal disorders Bronchospasm	3.5% 4/115 • 6 weeks Only patients who had at least one of the treatment related adverse events (AEs) was listed in the other (non Serious) AE table and was included as the total number of patients with Non-Serious Adverse Events.	5.4% 6/112 • 6 weeks Only patients who had at least one of the treatment related adverse events (AEs) was listed in the other (non Serious) AE table and was included as the total number of patients with Non-Serious Adverse Events.
Psychiatric disorders Insomnia	7.0% 8/115 • 6 weeks Only patients who had at least one of the treatment related adverse events (AEs) was listed in the other (non Serious) AE table and was included as the total number of patients with Non-Serious Adverse Events.	7.1% 8/112 • 6 weeks Only patients who had at least one of the treatment related adverse events (AEs) was listed in the other (non Serious) AE table and was included as the total number of patients with Non-Serious Adverse Events.
Psychiatric disorders Anxiety	1.7% 2/115 • 6 weeks Only patients who had at least one of the treatment related adverse events (AEs) was listed in the other (non Serious) AE table and was included as the total number of patients with Non-Serious Adverse Events.	5.4% 6/112 • 6 weeks Only patients who had at least one of the treatment related adverse events (AEs) was listed in the other (non Serious) AE table and was included as the total number of patients with Non-Serious Adverse Events.
Gastrointestinal disorders Diarrhoea	9.6% 11/115 • 6 weeks Only patients who had at least one of the treatment related adverse events (AEs) was listed in the other (non Serious) AE table and was included as the total number of patients with Non-Serious Adverse Events.	10.7% 12/112 • 6 weeks Only patients who had at least one of the treatment related adverse events (AEs) was listed in the other (non Serious) AE table and was included as the total number of patients with Non-Serious Adverse Events.
Gastrointestinal disorders Constipation	7.8% 9/115 • 6 weeks Only patients who had at least one of the treatment related adverse events (AEs) was listed in the other (non Serious) AE table and was included as the total number of patients with Non-Serious Adverse Events.	9.8% 11/112 • 6 weeks Only patients who had at least one of the treatment related adverse events (AEs) was listed in the other (non Serious) AE table and was included as the total number of patients with Non-Serious Adverse Events.
Gastrointestinal disorders Vomiting	5.2% 6/115 • 6 weeks Only patients who had at least one of the treatment related adverse events (AEs) was listed in the other (non Serious) AE table and was included as the total number of patients with Non-Serious Adverse Events.	5.4% 6/112 • 6 weeks Only patients who had at least one of the treatment related adverse events (AEs) was listed in the other (non Serious) AE table and was included as the total number of patients with Non-Serious Adverse Events.
Gastrointestinal disorders Nausea	4.3% 5/115 • 6 weeks Only patients who had at least one of the treatment related adverse events (AEs) was listed in the other (non Serious) AE table and was included as the total number of patients with Non-Serious Adverse Events.	6.2% 7/112 • 6 weeks Only patients who had at least one of the treatment related adverse events (AEs) was listed in the other (non Serious) AE table and was included as the total number of patients with Non-Serious Adverse Events.
Psychiatric disorders Depression	12.2% 14/115 • 6 weeks Only patients who had at least one of the treatment related adverse events (AEs) was listed in the other (non Serious) AE table and was included as the total number of patients with Non-Serious Adverse Events.	7.1% 8/112 • 6 weeks Only patients who had at least one of the treatment related adverse events (AEs) was listed in the other (non Serious) AE table and was included as the total number of patients with Non-Serious Adverse Events.
Psychiatric disorders Agitation	9.6% 11/115 • 6 weeks Only patients who had at least one of the treatment related adverse events (AEs) was listed in the other (non Serious) AE table and was included as the total number of patients with Non-Serious Adverse Events.	6.2% 7/112 • 6 weeks Only patients who had at least one of the treatment related adverse events (AEs) was listed in the other (non Serious) AE table and was included as the total number of patients with Non-Serious Adverse Events.