Imipenem/Relebactam/Cilastatin Versus Piperacillin/Tazobactam for Treatment of Participants With Bacterial Pneumonia (MK-7655A-014)

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02493764
• Date of registration: 07/07/2015
• Prospective Registration: Yes
• Primary sponsor: Merck Sharp & Dohme Corp.
• Public title: Imipenem/Relebactam/Cilastatin Versus Piperacillin/Tazobactam for Treatment of Participants With Bacterial Pneumonia (MK-7655A-014) RESTORE-IMI 2
• Scientific title: A Phase III, Randomized, Double-Blind, Active Comparator-Controlled Clinical Trial to Study the Safety, Tolerability, and Efficacy of Imipenem/Cilastatin/Relebactam (MK-7655A) Versus Piperacillin/Tazobactam in Subjects With Hospital-Acquired Bacterial Pneumonia or Ventilator-Associated Bacterial Pneumonia
• Date of first enrolment: November 24, 2015
• Target sample size: 537
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02493764
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 3

Countries of recruitment

Argentina, Australia, Brazil, Bulgaria, Canada, Colombia, Croatia, Czechia, Estonia, France, Georgia, Germany, Guatemala, Italy, Japan, Korea, Republic of, Latvia, Lithuania, Mexico, Norway, Peru, Philippines, Portugal, Romania, Russian Federation, Serbia, Spain, Turkey, Ukraine, United States

Contacts

• Name: Medical Director
• Affiliation: Merck Sharp & Dohme Corp.

Key inclusion & exclusion criteria

Inclusion Criteria:

- Requires treatment with IV antibiotic therapy for hospital-acquired bacterial
pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP)

- Fulfills clinical and radiographic criteria, with onset of criteria occurring after
more than 48 hours of hospitalization or within 7 days after discharge from a hospital
(for HABP); or at least 48 hours after mechanical ventilation (for VABP)

- Has an adequate baseline lower respiratory tract specimen obtained for Gram stain and
culture

- Has an infection known or thought to be caused by microorganisms susceptible to the IV
study therapy

- Agrees to allow any bacterial isolates obtained from protocol-required specimens
related to the current infection to be provided to the Central Microbiology Reference
Laboratory for study-related microbiological testing, long term storage, and other
future testing

- Is not of reproductive potential; or if of reproductive potential agrees to avoid
impregnating a partner or avoid becoming pregnant, by practicing abstinence or using
acceptable contraception

Exclusion Criteria:

- Has a baseline lower respiratory tract specimen Gram stain that shows the presence of
Gram-positive cocci only

- Has confirmed or suspected community-acquired bacterial pneumonia (CABP)

- Has confirmed or suspected pneumonia of viral, fungal or parasitic origin

- Has HABP/VABP caused by an obstructive process, including lung cancer or other known
obstruction

- Has a carcinoid tumor or carcinoid syndrome

- Has active immunosuppression defined as either receiving immunosuppressive medications
or having a medical condition associated with immunodeficiency

- Is expected to survive for less than 72 hours

- Has a concurrent condition or infection that would preclude evaluation of therapeutic
response

- Has received effective antibacterial drug therapy for the index infection of HABP/VABP
for more than 24 hours continuously, during the previous 72 hours

- Has a history of serious allergy, hypersensitivity or a serious reaction to any
penicillin or beta-lactamase inhibitors

- Female is pregnant, expecting to conceive, is breastfeeding or plans to breastfeed

- Has a history of seizure disorder requiring ongoing prior treatment with
anti-convulsive therapy within the last 3 years

- Anticipates treatment with the following: valproic acid or divalproex sodium,
serotonin re-uptake inhibitors, tricyclic antidepressants, or serotonin receptor
antagonists, meperidine, buspirone, concomitant systemic antibacterial agents,
antifungal or antiviral therapy for the index infection of HABP/VABP

- Is currently undergoing hemodialysis or peritoneal dialysis

- Is currently participating in, has participated in during the previous 30 days, or
anticipates to participate in any other clinical study involving the administration of
experimental medication

- Has previously participated in this study



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Bacterial Pneumonia

Intervention(s)

Drug: Linezolid

Drug: Cilastatin

Drug: Relebactam

Drug: Imipenem

Drug: Piperacillin

Drug: Tazobactam

Primary Outcome(s)

Percentage of Participants With All-cause Mortality (ACM) Through Day 28 in the Modified Intention-to-treat (MITT) Population [Time Frame: Up to 28 days]

Secondary Outcome(s)

Percentage of Participants in the CE Population With a FCR at OTX2 (Day 6) [Time Frame: Day 6 (OTX2)]

Percentage of Participants in the CE Population With a FCR at EFU Visit [Time Frame: Up to 16 days after end of therapy (up to Day 30)]

Percentage of Participants in the ME Population With a FMR at EFU Visit [Time Frame: Up to 16 days after end of therapy (up to Day 30)]

Percentage of Participants in the MITT Population With a Favorable Clinical Response (FCR) at Early Follow-up (EFU) Visit [Time Frame: Up to 16 days after end of therapy (up to 30 days)]

Percentage of Participants in the Clinically Evaluable (CE) Population With a FCR at On-therapy Visit 1 (OTX1) [Day 3] [Time Frame: Day 3 (OTX1)]

Percentage of Participants in the Microbiologically Evaluable (ME) Population With a FMR at EOT Visit [Time Frame: From Day 7 to Day 14]

Percentage of Participants in the MITT Population With a FCR at OTX1 (Day 3) [Time Frame: Day 3 (OTX1)]

Percentage of Participants With =1 Adverse Event (AE) [Time Frame: Up to 30 days]

Percentage of Participants in the MITT Population With a FCR at OTX2 (Day 6) [Time Frame: Day 6 (OTX2)]

Percentage of Participants Discontinuing Study Therapy Due to an AE [Time Frame: Up to 14 days]

Percentage of Participants in the CE Population With a FCR at OTX3 (Day 10) [Time Frame: Day 10 (OTX3)]

Percentage of Participants in the MITT Population With a FCR at EOT [Time Frame: From Day 7 to Day 14]

Percentage of Participants in the MITT Population With a FCR at OTX3 (Day 10) [Time Frame: Day 10 (OTX3)]

Percentage of Participants in the mMITT Population With a FMR at EFU Visit [Time Frame: Up to 16 days after end of therapy (up to Day 30)]

Percentage of Participants With ACM at EFU in the MITT Population [Time Frame: Up to 16 days after end of therapy (up to 30 days)]

Percentage of Participants With ACM at EFU in the mMITT Population [Time Frame: Up to 16 days after end of therapy (up to 30 days)]

Percentage of Participants in the CE Population With a FCR at EOT Visit [Time Frame: From Day 7 to Day 14]

Percentage of Participants in the mMITT Population With a Favorable Microbiological Response (FMR) at End of Treatment (EOT) Visit [Time Frame: From Day 7 to Day 14]

Percentage of Participants With ACM in the Microbiological Modified Intention-to-treat (mMITT) Population [Time Frame: Up to 28 days]

Percentage of Participants in the CE Population With a FCR at Day 28 [Time Frame: Day 28]

Percentage of Participants in the MITT Population With a FCR at Day 28 [Time Frame: Day 28]

Secondary ID(s)

MK-7655A-014

7655A-014

2015-000246-34

163240

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 16/04/2020
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02493764