An Effectiveness, Safety, and Microbiology Study of Doripenem in Patients With Nosocomial (Hospital-acquired) Pneumonia

• Sponsor: PriCara, Unit of Ortho-McNeil, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00502801
• Collaborator: (none)
• Enrollment: 185
• Locations: 40
• Arm: 1
• Duration (Months): 15
• Patients Per Site: 4.6
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the effectiveness and safety of doripenem monohydrate in the treatment of patients with nosocomial (hospital-acquired) pneumonia.

Condition or Disease	Intervention/Treatment	Phase
Pneumonia; Bacterial Pneumonia; Ventilator-Associated Pneumonia; Infections, Nosocomial	Drug: doripenem	Phase 2

Detailed Description

Nosocomial pneumonia (NP) accounts for approximately 15% of all hospital-acquired infections. The incidence of NP rises in patients who are on breathing machines. The death rate for NP can be as high as 30%. NP caused by bacteria, such as Pseudomonas aeruginosa, has been associated with an increased death rate compared to other pathogens. Prompt use of appropriate antibiotics is essential. Compounding the issue of nosocomial infections is the increasing rate to which bacteria develop resistance to antibiotics. This hospital based trial is studying doripenem in patients who have nosocomial pneumonia to see if it is effective against bacteria associated with this serious bacterial infection. The duration of treatment can be anywhere from 8 to 14 days. Safety evaluations, such as vital signs and laboratory tests will be performed upon enrollment, after 4 days on therapy, after 9 days on therapy for those on greater than 8 days, at the end of therapy, 7 to 14 days after the end of therapy, and 28 to 35 days after the end of therapy. Adverse events will be collected throughout the study. Clinical response to doripenem therapy will be assessed 7 to 14 days after the end of therapy and the long-term clinical response to doripenem therapy will be assessed 28 to 35 days after the end of therapy. Doripenem IV will be administered for a duration of treatment from 8 to 14 days.

Study Design

• Study Type: Interventional
• Actual Enrollment: 185 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study of Doripenem In The Treatment of Nosocomial and Ventilator-Associated Pneumonia In Hospitals
• Study Start Date: Aug 1, 2007
• Actual Primary Completion Date: Nov 1, 2008
• Actual Study Completion Date: Nov 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Doripenem 1g i.v. infused over 4 hours every 8 hours for 8 to 14 days	Drug: doripenem; 1g i.v. infused over 4 hours every 8 hours for 8 to 14 days

Outcome Measures

Primary Outcome Measures

1. Clinical Response Rates and 95% Confidence Intervals at the Test-of-Cure Assessment. [5 to 21 days after the last dose of study therapy, or at early termination.]

   The table below shows the percentage of subjects who had a clinical response of "clinical cure" at the Late Follow-up Visit as assigned by the medical monitor. A clinical response of "clinical cure" is defined as no further antibacterial therapy needed for treatment of the infection.

Secondary Outcome Measures

1. Clinical Response Rates at the Late Follow-up Assessment. [28 to 35 days after last dose of study therapy]

   The table below shows the percentage of subjects who had a clinical response of "clinical cure" at the Late Follow-up Visit as assigned by the medical monitor. A clinical response of "clinical cure" is defined as no further antibacterial therapy needed for treatment of the infection.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients suffering from Nosocomial Pneumonia or Ventilator-Associated Pneumonia

• All patients must be hospitalized throughout the treatment period

• Patients must have microbiological samples (respiratory secretions) suitable for culture and microscopy

Exclusion Criteria:

• Known or suspected severe kidney impairment

• Known or suspected liver dysfunction

• Treatment with any investigational drug or device within 30 days before enrollment

• Patients with one or more of the following: cystic fibrosis, lung abscess, active tuberculosis

• Women who are pregnant or lactating

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Palm Springs	California	United States
2		San Francisco	California	United States
3		Denver	Colorado	United States
4		Washington	District of Columbia	United States
5		Jacksonville	Florida	United States
6		Miami	Florida	United States
7		Atlanta	Georgia	United States
8		Decatur	Georgia	United States
9		Hazard	Kentucky	United States
10		Baltimore	Maryland	United States
11		Springfield	Massachusetts	United States
12		Grand Rapids	Michigan	United States
13		Columbia	Missouri	United States
14		Saint Louis	Missouri	United States
15		Omaha	Nebraska	United States
16		Buffalo	New York	United States
17		Flushing	New York	United States
18		Jamaica	New York	United States
19		Toledo	Ohio	United States
20		Providence	Rhode Island	United States
21		Johnson City	Tennessee	United States
22		Nashville	Tennessee	United States
23		Norfolk	Virginia	United States
24		Morgantown	West Virginia	United States
25		Buenos Aires		Argentina
26		Santa Fe		Argentina
27		Oshawa	Ontario	Canada
28		Chicoutimi	Quebec	Canada
29		Concepcion		Chile
30		Avenija Gojka Suska 6		Croatia
31		Zagreb		Croatia
32		Argenteuil 95 95		France
33		Jaipur		India
34		Kozhikode		India
35		Manipal		India
36		Noida		India
37		Pune		India
38		Novosibirsk		Russian Federation
39		Kharkiv		Ukraine
40		Ukraine Poltava		Ukraine

Sponsors and Collaborators

• PriCara, Unit of Ortho-McNeil, Inc.

Investigators

• Study Director: PriCara, Unit of Ortho-McNeil, Inc. Clinical Trial, PriCara, Unit of Ortho-McNeil, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: PriCara, Unit of Ortho-McNeil, Inc.
• ClinicalTrials.gov Identifier: NCT00502801
• Other Study ID Numbers: CR012931; DORIINI2002
• First Posted: Jul 18, 2007
• Last Update Posted: Sep 25, 2013
• Last Verified: Sep 1, 2013

• Keywords provided by PriCara, Unit of Ortho-McNeil, Inc.: Pneumonia; Lung Infection; Bacterial Infection; Hospital-Acquired Infection; Ventilator Infection; Antibiotic Therapy
• Additional relevant MeSH terms: Infections; Pneumonia; Pneumonia, Ventilator-Associated; Pneumonia, Bacterial; Cross Infection; Doripenem

Study Results

Participant Flow

Pre-assignment Detail	Two enrolled subjects didn't take study medication and weren't qualified for safety population.

Arm/Group Title	Doripenem
Arm/Group Description	1g i.v. infused over 4 hours every 8 hours from day 1 to day 8 to 14, depending on length of treatment
Period Title: Treatment Period
STARTED	183
COMPLETED	129
NOT COMPLETED	54
Period Title: Treatment Period
STARTED	129
COMPLETED	121
NOT COMPLETED	8

Baseline Characteristics

Arm/Group Title	Doripenem
Arm/Group Description	1g i.v. infused over 4 hours every 8 hours from day 1 to day 8 to 14, depending on length of treatment
Overall Participants	183
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56 (20.23)
Sex: Female, Male (Count of Participants)
Female	71 38.8%
Male	112 61.2%
Region of Enrollment (participants) [Number]
ARGENTINA	4 2.2%
CANADA	6 3.3%
CHILE	9 4.9%
CROATIA	21 11.5%
FRANCE	6 3.3%
INDIA	10 5.5%
RUSSIA	2 1.1%
UKRAINE	5 2.7%
USA	120 65.6%
race (participants) [Number]
AMERICAN INDIAN OR ALASKA	2 1.1%
ASIAN	14 7.7%
BLACK OR AFRICAN AMERICAN	14 7.7%
OTHER, SPECIFY	2 1.1%
WHITE	151 82.5%
ethnicity (participants) [Number]
HISPANIC OR LATINO	20 10.9%
NOT HISPANIC OR LATINO	158 86.3%
OTHER	5 2.7%
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	27.4 (8.63)

Outcome Measures

1. Primary Outcome

Title	Clinical Response Rates and 95% Confidence Intervals at the Test-of-Cure Assessment.
Description	The table below shows the percentage of subjects who had a clinical response of "clinical cure" at the Late Follow-up Visit as assigned by the medical monitor. A clinical response of "clinical cure" is defined as no further antibacterial therapy needed for treatment of the infection.
Time Frame	5 to 21 days after the last dose of study therapy, or at early termination.

Outcome Measure Data

Analysis Population Description

Clinically Evaluable: Subset of the ITT population who received at least 5 days of study medication unless deemed a clinical failure with at least 2 full days of therapy, and excluding those subjects with a clinical outcome of Not Evaluable at the TOC assessment.

Arm/Group Title	Doripenem
Arm/Group Description	1g i.v. infused over 4 hours every 8 hours from day 1 to day 8 to 14, depending on length of treatment
Measure Participants	122
All Clinically Evaluable Subjects	63.9 34.9%
Subjects with Nosocomial Pneumonia	66.0 36.1%
Subjects with Ventilator Associated Pneumonia	64.4 35.2%
Subjects with Healthcare Associated Pneumonia	50.0 27.3%

2. Secondary Outcome

Title	Clinical Response Rates at the Late Follow-up Assessment.
Description	The table below shows the percentage of subjects who had a clinical response of "clinical cure" at the Late Follow-up Visit as assigned by the medical monitor. A clinical response of "clinical cure" is defined as no further antibacterial therapy needed for treatment of the infection.
Time Frame	28 to 35 days after last dose of study therapy

Outcome Measure Data

Analysis Population Description

Clinically Evaluable: Subset of the ITT population who received at least 5 days of study medication unless deemed a clinical failure with at least 2 full days of therapy, and excluding those subjects with a clinical outcome of Not Evaluable at the TOC assessment.

Arm/Group Title	Doripenem
Arm/Group Description	1g i.v. infused over 4 hours every 8 hours from day 1 to day 8 to 14, depending on length of treatment
Measure Participants	78
All Clinically Evaluable Subjects	83.3 45.5%
Subjects with Nosocomial Pneumonia	82.9 45.3%
Subjects with Ventilator Associated Pneumonia	84.2 46%
Subjects with Healthcare Associated Pneumonia	80.0 43.7%

Adverse Events

Arm/Group Title	Doripenem
Arm/Group Description	1g i.v. infused over 4 hours every 8 hours from day 1 to day 8 to 14, depending on length of treatment
All Cause Mortality
	Doripenem
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Doripenem
	Affected / at Risk (%)	# Events
Total	70/183 (38.3%)
Blood and lymphatic system disorders
Neutropenia	1/183 (0.5%)
Cardiac disorders
Bradycardia	1/183 (0.5%)
Cardiac Arrest	6/183 (3.3%)
Cardiac Failure Congestive	2/183 (1.1%)
Cardio-Respiratory Arrest	6/183 (3.3%)
Cardiopulmonary Failure	1/183 (0.5%)
Myocardial Infarction	1/183 (0.5%)
Pericardial Effusion	1/183 (0.5%)
Ventricular Fibrillation	1/183 (0.5%)
Congenital, familial and genetic disorders
Sickle Cell Anaemia	1/183 (0.5%)
Spondylolisthesis	1/183 (0.5%)
Gastrointestinal disorders
Gastric Ulcer	1/183 (0.5%)
Gastrointestinal Haemorrhage	1/183 (0.5%)
Impaired Gastric Emptying	1/183 (0.5%)
Localised Intraabdominal Fluid Collection	1/183 (0.5%)
Pancreatic Fistula	1/183 (0.5%)
General disorders
Multi-Organ Failure	1/183 (0.5%)
Ulcer	1/183 (0.5%)
Infections and infestations
Bacteraemia	1/183 (0.5%)
Candidiasis	1/183 (0.5%)
Empyema	1/183 (0.5%)
Lung Infection Pseudomonal	1/183 (0.5%)
Meningitis Bacterial	1/183 (0.5%)
Meningoencephalitis Herpetic	1/183 (0.5%)
Pneumonia	9/183 (4.9%)
Postoperative Wound Infection	1/183 (0.5%)
Pyelonephritis	1/183 (0.5%)
Renal Abscess	1/183 (0.5%)
Retroperitoneal Abscess	1/183 (0.5%)
Sepsis	4/183 (2.2%)
Septic Shock	1/183 (0.5%)
Sinusitis	1/183 (0.5%)
Wound Infection	1/183 (0.5%)
Injury, poisoning and procedural complications
Feeding Tube Complication	1/183 (0.5%)
Head Injury	1/183 (0.5%)
Subdural Haematoma	1/183 (0.5%)
Traumatic Brain Injury	2/183 (1.1%)
Weaning Failure	1/183 (0.5%)
Investigations
White Blood Cell Count Increased	1/183 (0.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bile Duct Cancer	1/183 (0.5%)
Gastric Cancer	1/183 (0.5%)
Nervous system disorders
Anoxic Encephalopathy	1/183 (0.5%)
Cerebral Ischaemia	1/183 (0.5%)
Coma	1/183 (0.5%)
Convulsion	1/183 (0.5%)
Psychomotor Hyperactivity	1/183 (0.5%)
Renal and urinary disorders
Haematuria	1/183 (0.5%)
Obstructive Uropathy	1/183 (0.5%)
Renal Failure	2/183 (1.1%)
Renal Failure Acute	1/183 (0.5%)
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Distress Syndrome	4/183 (2.2%)
Acute Respiratory Failure	1/183 (0.5%)
Atelectasis	1/183 (0.5%)
Chronic Obstructive Pulmonary Disease	1/183 (0.5%)
Hydropneumothorax	1/183 (0.5%)
Hypoxia	2/183 (1.1%)
Pleural Effusion	3/183 (1.6%)
Pneumonia Aspiration	3/183 (1.6%)
Pulmonary Oedema	1/183 (0.5%)
Respiratory Arrest	4/183 (2.2%)
Respiratory Distress	2/183 (1.1%)
Respiratory Failure	9/183 (4.9%)
Skin and subcutaneous tissue disorders
Rash Papular	1/183 (0.5%)
Vascular disorders
Air Embolism	1/183 (0.5%)
Haematoma	1/183 (0.5%)
Haemorrhage	1/183 (0.5%)
Hypertension	1/183 (0.5%)
Hypotension	2/183 (1.1%)
Other (Not Including Serious) Adverse Events
	Doripenem
	Affected / at Risk (%)	# Events
Total	93/183 (50.8%)
Blood and lymphatic system disorders
Anaemia	16/183 (8.7%)
Thrombocythaemia	11/183 (6%)
Gastrointestinal disorders
Constipation	14/183 (7.7%)
Diarrhoea	22/183 (12%)
Nausea	14/183 (7.7%)
Vomiting	10/183 (5.5%)
General disorders
Pyrexia	12/183 (6.6%)
Infections and infestations
Fungal Infection	17/183 (9.3%)
Urinary Tract Infection	12/183 (6.6%)
Metabolism and nutrition disorders
Hypoglycaemia	10/183 (5.5%)
Hypokalaemia	21/183 (11.5%)
Vascular disorders
Hypertension	13/183 (7.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.