Efficacy and Safety of Imipenem+Cilastatin/Relebactam (MK-7655A) Versus Colistimethate Sodium+Imipenem+Cilastatin in Imipenem-Resistant Bacterial Infection (MK-7655A-013)

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02452047
• Date of registration: 20/05/2015
• Prospective Registration: Yes
• Primary sponsor: Merck Sharp & Dohme Corp.
• Public title: Efficacy and Safety of Imipenem+Cilastatin/Relebactam (MK-7655A) Versus Colistimethate Sodium+Imipenem+Cilastatin in Imipenem-Resistant Bacterial Infection (MK-7655A-013) RESTORE-IMI 1
• Scientific title: A Phase III, Randomized, Double-Blind, Active Comparator-Controlled Clinical Trial to Estimate the Efficacy and Safety of Imipenem/Cilastatin/Relebactam (MK-7655A) Versus Colistimethate Sodium + Imipenem/Cilastatin in Subjects With Imipenem-Resistant Bacterial Infection
• Date of first enrolment: August 21, 2015
• Target sample size: 50
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02452047
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 3

Countries of recruitment

Brazil, Colombia, Estonia, Germany, Greece, Italy, Japan, Korea, Republic of, Latvia, Lithuania, Mexico, Peru, Romania, South Africa, Turkey, Ukraine, United States

Contacts

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

Key inclusion & exclusion criteria

Inclusion Criteria:

- Hospitalization that requires treatment with IV antibiotic therapy for a new,
persistent or progressing bacterial infection involving at least 1 of 3 primary
infection types (HABP, VABP, cIAI, or cUTI)

- Positive culture data from the primary infection-site specimen collected within 1 week
of study entry. At least one of the suspected causative pathogens from the specimen
meets all of the following: 1) identified as a Gram-negative bacterium, 2)
culture-confirmed imipenem resistance (and colistin resistance for Group 3 only), 3)
culture-confirmed susceptibility to imipenem/relebactam and to colistin (for Groups 1
and 2 only)

- Not of reproductive potential, or of reproductive potential and agrees to avoid
becoming pregnant or impregnating a partner by complying with one of the following: 1)
practice abstinence, or 2) use of acceptable contraception during heterosexual
activity

Exclusion Criteria:

- Concurrent infection (endocarditis, osteomyelitis, meningitis, prosthetic joint
infection, disseminated fungal infection, or active pulmonary tuberculosis) that would
interfere with evaluation of the response to the study antibiotics

- Received treatment with any form of systemic colistin for >24 hours within 72 hours
before initiation of study drug (for Groups 1 and 2 only)

- HABP or VABP caused by an obstructive process

- cUTI which meets any of the following: 1) complete obstruction of any portion of the
urinary tract, 2) known ileal loop, 3) intractable vesico-ureteral reflux, 4) presence
of an indwelling urinary catheter which cannot be removed at study entry

- History of serious allergy, hypersensitivity, or any serious reaction to listed
antibiotics (per-protocol)

- Female who is pregnant or is expecting to conceive (or a male partner of a female who
is expecting to conceive), is breastfeeding, or plans to breastfeed before completion
of the study

- Anticipated treatment with any of the following during the study: valproic acid or
divalproex sodium, or concomitant systemic (e.g. IV, oral or inhaled) antimicrobial
agents with known Gram-negative bacterial coverage

- Currently undergoing hemodialysis or peritoneal dialysis

- Participated or anticipates participating in any other clinical study involving
administration of investigational medication up to 30 days before screening or during
the course of the trial



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

Health Condition(s) or Problem(s) studied

Bacterial Infections

Intervention(s)

Drug: Colistimethate sodium (CMS)

Drug: Imipenem+Cilastatin/Relebactam

Drug: Imipenem+Cilastatin

Drug: Placebo to CMS

Primary Outcome(s)

Percentage of Participants Discontinuing From Study Therapy Due to =1 AEs [Time Frame: Up to Day 21]

Analysis of Specific AEs With an Incidence of =4 Participants in a Treatment Group [Time Frame: Up to Day 35 (up to 14 days after completing study treatment)]

Percentage of Participants With =1 Serious Adverse Events (SAEs) [Time Frame: Up to Day 35 (up to 14 days after completing study treatment)]

Percentage of Participants Discontinuing From Study Therapy Due to =1 Drug-Related AEs [Time Frame: Up to Day 21]

Percentage of Participants With Favorable Overall Response (FOR) [Time Frame: Up to Day 30 (up to 9 days after completing study treatment)]

Percentage of Participants With =1 Adverse Events (AEs) [Time Frame: Up to Day 35 (up to 14 days after completing study treatment)]

Percentage of Participants With =1 Drug-Related AEs [Time Frame: Up to Day 35 (up to 14 days after completing study treatment)]

Percentage of Participants With =1 Drug-Related SAEs [Time Frame: Up to Day 35 (up to 14 days after completing study treatment)]

Percentage of Participants With =1 Events of Clinical Interest (ECI) [Time Frame: Up to Day 35 (up to 14 days after completing study treatment)]

Secondary Outcome(s)

Percentage of Participants With =1 Events of Treatment-Emergent Nephrotoxicity [Time Frame: Up to Day 35 (up to 14 days after completing study treatment)]

Percentage of Participants With All-cause Mortality Up to Day 28 [Time Frame: Up to Day 28]

Percentage of Participants With Favorable Clinical Response (FCR) at Day 28 [Time Frame: Day 28]

Percentage of cUTI Participants With Favorable Microbiological Response (FMR) at OTX [Time Frame: OTX (Day 3)]

Percentage of cUTI Participants With FMR at EFU [Time Frame: EFU (Between Day 10 and Day 30 [5 to 9 Days after EOT])]

Percentage of cUTI Participants With FMR at EOT [Time Frame: At EOT (up to Day 21)]

Percentage of Participants With FCR at EFU [Time Frame: EFU (Between Day 10 and Day 30 [5 to 9 Days after EOT])]

Percentage of Participants With FCR on Therapy (OTX) [Time Frame: OTX (Day 3)]

Percentage of Participants With FCR at End of Therapy (EOT) [Time Frame: At EOT (up to Day 21)]

Secondary ID(s)

163367

7655A-013

2015-000066-62

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 19/10/2018
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02452047