A Safety and Tolerability Study of Doripenem in Patients With Abdominal Infections or Pneumonia

NCT ID: NCT00515034

Last Updated: 2019-03-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 146 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-10-31
• Study Completion Date: 2008-11-30

Brief Summary

The purpose of this study is to assess the safety and tolerability of doripenem compared to imipenem in Ventilator-assisted pneumonia and complicated Intra-abdominal Infection. The study population will include hospitalized patients (or patients resident in a chronic health care facility) who have a diagnosis of either Ventilator associated pneumonia or complicated Intra-abdominal Infection.

Detailed Description

This is a randomized (study drug assigned by chance), open-label (all people involved know the identity of the intervention), multicenter study that will evaluate the safety and tolerability of doripenem (an antibiotic used to treat infections) in patients with ventilator-associated pneumonia (VAP) or complicated intra-abdominal infection (cIAI). Approximately 250 patients will be assigned in a 3:1 ratio to receive doripenem or imipenem/cilastatin (188 patients randomized to receive doripenem and 62 patients randomized to receive imipenem/cilastatin). Furthermore, patients who receive doripenem or imipenem/cilastatin will be stratified by disease (VAP or cIAI). Therefore, for reporting purposes, there will be 4 groups: Patients with VAP treated with doripenem, patients with VAP treated with imipenem/cilastatin, patients with cIAI treated with doripenem, and patients with cIAI treated with imipenem/cilastatin. Study drug will be administered intravenously (iv) (through a vein) for 7 to 14 days for patients with VAP and for 5 to 14 days for patients with cIAI. The maximum duration of study drug is 14 days. Vancomycin and/or amikacin may be added to the study drug regimen as adjunctive therapy for those patients who meet study specified criteria. The recommended dosage of vancomycin is 1 g every 12 hours administered by iv infusion. The addition of amikacin is at the discretion of the investigator for patients with VAP (not cIAI) and the recommended dosing regimen for amikacin is 15 mg/kg given iv once a day. Alternative amikacin regimens or other aminoglycoside regimens may be permitted. Safety will be assessed during the study by the monitoring of adverse events, evaluation of laboratory test results, and changes in vital signs. The primary endpoint of this study is to assess the overall incidence of treatment-emergent adverse events (TEAEs) from the initiation of the first infusion of study drug and up to 30 days after the completion of study drug therapy. Treatment-emergent adverse events are defined as adverse events that occur or worsen between the initial infusion of study drug up to 30 days after the last dose of study drug. The hypothesis for this study is that doripenem has a similar safety profile to imipenem. Doripenem (1g at 8-hour intervals over a period of 4 hours) or imipenem/cilastatin (1g at 8-hours over a period of 1 hour) will be administered by intravenous (iv) infusion (delivery of drug slowly into the vein over a period of time). Patients diagnosed with ventilator associated pneumonia (VAP) will be treated for 7 to 14 days and patients with complicated intra-abdominal infections (cIAI) will be treated for 5 to 14 days.

Conditions

Pneumonia, Ventilator-Associated; Pneumonia, Bacterial; Pneumonia; Abdominal Abscess; Bacterial Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

001

Doripenem 1 gram infused over 4 hours at 8-hour intervals for patients with Ventilator-Associated Pneumonia (VAP) for 7 to 14 days Vancomycin and/or amikacin may be added as adjunctive therapy as per investigator discretion

Group Type: EXPERIMENTAL

Doripenem

Intervention Type: DRUG

1 gram infused over 4 hours at 8-hour intervals for patients with Ventilator-Associated Pneumonia (VAP) for 7 to 14 days

002

Imipenem/cilastatin 1 gram infused over 1 hour at 8 hour intervals for patients with Ventilator-Associated Pneumonia (VAP) for 7 to 14 days Vancomycin and/or amikacin may be added as adjunctive therapy as per investigator discretion

Group Type: ACTIVE_COMPARATOR

Imipenem/cilastatin

Intervention Type: DRUG

Vancomycin and/or amikacin may be added as adjunctive therapy as per investigator discretion

003

Doripenem 1 gram infused over 4 hours at 8 hour intervals for patients with complicated intrabdominal infections (cIAI) for 5 to 14 days Vancomycin may be added as adjunctive therapy as per investigator discretion

Group Type: EXPERIMENTAL

Doripenem

Intervention Type: DRUG

1 gram infused over 1 hour at 8 hour intervals for patients with Ventilator-Associated Pneumonia (VAP) for 7 to 14 days

004

Imipenem/cilastatin 1 gram infused over 1 hour at 8 hour intervals for patients with complicated intrabdominal infections (cIAI) for 5 to 14 days Vancomycin may be added as adjunctive therapy as per investigator discretion

Group Type: ACTIVE_COMPARATOR

Imipenem/cilastatin

Intervention Type: DRUG

Vancomycin and/or amikacin may be added as adjunctive therapy as per investigator discretion

Interventions

Imipenem/cilastatin

Vancomycin and/or amikacin may be added as adjunctive therapy as per investigator discretion

Intervention Type: DRUG

Imipenem/cilastatin

Vancomycin and/or amikacin may be added as adjunctive therapy as per investigator discretion

Intervention Type: DRUG

Doripenem

1 gram infused over 4 hours at 8-hour intervals for patients with Ventilator-Associated Pneumonia (VAP) for 7 to 14 days

Intervention Type: DRUG

Doripenem

1 gram infused over 1 hour at 8 hour intervals for patients with Ventilator-Associated Pneumonia (VAP) for 7 to 14 days

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients must be hospitalized with a diagnosis of Ventilator-Assisted Pneumonia (VAP) or complicated Intra-Abdominal Infection (cIAI)
• Patients with VAP must have been hospitalized (or been in a chronic care facility) for >= 5 days, have received mechanical ventilation for >= 48 hours, have a Clinical Pulmonary Infection Score (CPIS) of >= 5, have new or progressive radiographic infiltrates (not related to another disease process)
• Patients with cIAI must have clinical evidence of intra-abdominal infection, abdominal pain or tenderness, localized or diffuse abdominal wall rigidity, mass, ileus or have a requirement for surgical intervention (e.g., laparotomy, laparoscopic surgery, or percutaneous draining of an abscess) within 24 hours of study entry

Exclusion Criteria

• Patients with a history of acute hepatic failure or acute decompensation of chronic hepatic failure, history of severe impairment of renal function, history of immunocompromising illness, acquired immunodeficiency syndrome (AIDS), or human immunodeficiency virus (HIV) with a CD4 count less than 200 cells/mL within the past 6 months
• organ (including bone marrow) transplant recipients
• hematologic malignancy
• use of immunosuppressive therapy at screening, including use of high dose corticosteroids (e.g., > 40 mg prednisone or equivalent per day for > 2 weeks)
• history of any rapidly progressing disease or immediately life-threatening illness (including acute hepatic failure and septic shock)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

INDUSTRY

Sponsor Role: lead

Responsible Party

Johnson & Johnson Pharmaceutical Research and Development, L.L.C.

Principal Investigators

Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial

Role: STUDY_DIRECTOR

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Other Identifiers

DORINOS2001

Identifier Type: -

Identifier Source: secondary_id

CR012934

Identifier Type: -

Identifier Source: org_study_id