The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02493764




Registration number
NCT02493764
Ethics application status
Date submitted
7/07/2015
Date registered
7/07/2015
Date last updated
7/03/2019

Titles & IDs
Public title
Imipenem/Relebactam/Cilastatin Versus Piperacillin/Tazobactam for Treatment of Participants With Bacterial Pneumonia (MK-7655A-014)
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
Secondary ID [1] 0 0
2015-000246-34
Secondary ID [2] 0 0
7655A-014
Universal Trial Number (UTN)
Trial acronym
RESTORE-IMI 2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bacterial Pneumonia 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Imipenem
Treatment: Drugs - Relebactam
Treatment: Drugs - Cilastatin
Treatment: Drugs - Piperacillin
Treatment: Drugs - Tazobactam
Treatment: Drugs - Linezolid

Experimental: IMI/REL - Imipenem 500 mg + relebactam 250 mg + cilastatin 500 mg as a FDC administered intravenously (IV) every 6 hours for a minimum of 7 days, up to 14 days. At study entry open label linezolid 600 mg will also be administered by IV every 12 hours for up to 14 days.

Active Comparator: PIP/TAZ - Piperacillin 4000 mg + tazobactam 500 mg as a FDC administered IV every 6 hours for a minimum of 7 days, up to 14 days. At study entry open label linezolid 600 mg will also be administered by IV every 12 hours for up to 14 days.


Treatment: Drugs: Imipenem
Imipenem 500 mg as part of a FDC administered by IV every 6 hours for a minimum of 7 days, up to 14 days

Treatment: Drugs: Relebactam
Relebactam 250 mg as part of a FDC administered by IV every 6 hours for a minimum of 7 days, up to 14 days

Treatment: Drugs: Cilastatin
Cilastatin 500 mg as part of a FDC administered by IV every 6 hours for a minimum of 7 days, up to 14 days

Treatment: Drugs: Piperacillin
Piperacillin 4000 mg as part of a FDC administered by IV every 6 hours for a minimum of 7 days, up to 14 days

Treatment: Drugs: Tazobactam
Tazobactam 500 mg as part of a FDC administered by IV every 6 hours for a minimum of 7 days, up to 14 days

Treatment: Drugs: Linezolid
Linezolid 600 mg administered open-label by IV every 12 hours for up to 14 days

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of participants surviving at Day 28
Timepoint [1] 0 0
Day 28
Secondary outcome [1] 0 0
Percentage of participants with a favorable clinical response at early follow up visit
Timepoint [1] 0 0
Up to 16 days after end of therapy (up to Day 30)

Eligibility
Key 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 hour 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Merck Sharp & Dohme - North Ryde
Recruitment postcode(s) [1] 0 0
- North Ryde
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Iowa
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
Argentina
State/province [8] 0 0
Buenos Aires
Country [9] 0 0
Brazil
State/province [9] 0 0
Sao Paulo
Country [10] 0 0
Bulgaria
State/province [10] 0 0
Sofia
Country [11] 0 0
Canada
State/province [11] 0 0
Quebec
Country [12] 0 0
Colombia
State/province [12] 0 0
Bogota
Country [13] 0 0
Croatia
State/province [13] 0 0
Zagreb
Country [14] 0 0
Czechia
State/province [14] 0 0
Prague
Country [15] 0 0
Estonia
State/province [15] 0 0
Tallinn
Country [16] 0 0
France
State/province [16] 0 0
Paris
Country [17] 0 0
Georgia
State/province [17] 0 0
Tbilisi
Country [18] 0 0
Guatemala
State/province [18] 0 0
Guatemala
Country [19] 0 0
Italy
State/province [19] 0 0
Rome
Country [20] 0 0
Japan
State/province [20] 0 0
Chiyoda-Ku, Tokyo
Country [21] 0 0
Korea, Republic of
State/province [21] 0 0
Seoul
Country [22] 0 0
Latvia
State/province [22] 0 0
Riga
Country [23] 0 0
Lithuania
State/province [23] 0 0
Vilnius
Country [24] 0 0
Mexico
State/province [24] 0 0
Mexico City
Country [25] 0 0
Norway
State/province [25] 0 0
Drammen
Country [26] 0 0
Peru
State/province [26] 0 0
Lima
Country [27] 0 0
Philippines
State/province [27] 0 0
Makati
Country [28] 0 0
Portugal
State/province [28] 0 0
Paco D'arcos
Country [29] 0 0
Russian Federation
State/province [29] 0 0
Moscow
Country [30] 0 0
Serbia
State/province [30] 0 0
Belgrade
Country [31] 0 0
Spain
State/province [31] 0 0
Madrid
Country [32] 0 0
Turkey
State/province [32] 0 0
Istanbul
Country [33] 0 0
Ukraine
State/province [33] 0 0
Kiev

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Merck Sharp & Dohme Corp.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study aims to compare treatment with imipenem/relebactam/cilastatin (IMI/REL) as a
fixed-dose combination (FDC) with piperacillin/tazobactam (PIP/TAZ) FDC in participants with
hospital-acquired and ventilator-associated bacterial pneumonia. The primary hypothesis is
that IMI/REL is non-inferior to PIP/TAZ in the incidence rate of all-cause mortality.
Trial website
https://clinicaltrials.gov/show/NCT02493764
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme Corp.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Toll Free Number
Address 0 0
Country 0 0
Phone 0 0
1-888-577-8839
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02493764