Imipenem/Cilastatin/Relebactam (MK-7655A) Versus Piperacillin/Tazobactam in Participants With Hospital-Acquired or Ventilator-Associated Bacterial Pneumonia (MK-7655A-016)

NCT03583333 | Completed Phase 3 Results FDA Drug

• 4 other identifiers: 7655A-016MK-7655A-016PHRR190814-0021772018-003202-82
• Study Type: interventional
• Target: 274
• Locations: 8 countries
• Sites: 68

Brief Summary

This study will evaluate the efficacy and safety of a FDC of imipenem/cilastatin (IMI) and relebactam (REL) \[IMI/REL, MK-7655A\] compared to piperacillin/tazobactam (PIP/TAZ) in the treatment of adults diagnosed with Hospital-Acquired Bacterial Pneumonia (HABP) or Ventilator-Associated Bacterial Pneumonia (VABP). The primary hypothesis is that IMI/REL is non-inferior to PIP/TAZ as measured by the incidence rate of all-cause mortality through Day 28 post-randomization.

Conditions

Hospital-Acquired Bacterial Pneumonia; Ventilator-Associated Bacterial Pneumonia

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With All-cause Mortality Through Day 28 in the Modified Intent to Treat (MITT) Population

  For each participant, survival status was assessed at Day 28 post-randomization and recorded on the electronic Case Report Form. The percentage of participants with all-cause mortality through Day 28 in the MITT population is presented.

  Up to approximately 28 days

Secondary Outcomes (9)

• Percentage of Participants Achieving a Favorable Clinical Response at Early Follow-up (EFU) Visit in the MITT Population

  Up to approximately 27 days

• Percentage of Participants Achieving a Favorable Clinical Response at EFU Visit in the Clinically Evaluable (CE) Population

  Up to approximately 27 days

• Percentage of Participants Achieving a Favorable Clinical Response at End of Therapy (EOT) Visit in the MITT Population

  Up to approximately 14 days

• Percentage of Participants Achieving a Favorable Clinical Response at EOT Visit in the Clinically Evaluable (CE) Population

  Up to approximately 14 days

• Percentage of Participants Achieving a Favorable Microbiological Response at EOT Visit in Microbiological Modified Intent-To-Treat Population (mMITT) Population

  Up to approximately 14 days

Study Arms (2)

IMI/REL FDC

EXPERIMENTAL

Imipenem/cilastatin/relebactam (IMI/REL) administered intravenously (IV) as a fixed-dose combination (FDC) at a dosage of 500 mg IMI/250 mg REL, once every 6 hours for a minimum 7 days, up to 14 days. At the start of IMI/REL treatment, participants will be treated empirically with 600 mg open-label linezolid administered IV every 12 hours until methicillin-resistant Staphylococcus aureus (MRSA) is ruled out. Participants with confirmed MRSA infection will continue to receive 600 mg linezolid every 12 hours for a minimum of 7 days, up to 14 days total.

Drug: IMI/REL FDC; Drug: Linezolid

PIP/TAZ FDC

ACTIVE COMPARATOR

Piperacillin/tazobactam (PIP/TAZ ) administered IV as a FDC at a dosage of 4000 mg PIP/500 mg TAZ once every 6 hours for a minimum 7 days, up to 14 days. At the start of PIP/TAZ treatment, participants will be treated empirically with 600 mg open-label linezolid administered IV every 12 hours until methicillin-resistant Staphylococcus aureus (MRSA) is ruled out. Participants with confirmed MRSA infection will continue to receive 600 mg linezolid every 12 hours for a minimum of 7 days, up to 14 days total.

Drug: PIP/TAZ FDC; Drug: Linezolid

Interventions

IMI/REL FDC DRUG

500 mg Imipenem, 500 mg Cilastatin and 250 mg Relebactam powder FDC provided in a single vial

Also known as: MK-7655A

IMI/REL FDC

PIP/TAZ FDC DRUG

4000 mg Piperacillin and 500 mg Tazobactam powder FDC provided in a single vial

PIP/TAZ FDC

Linezolid DRUG

Open-label 600 mg Linezolid

IMI/REL FDC; PIP/TAZ FDC

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Requires treatment with IV antibiotic therapy for HABP or VABP
• Fulfills clinical and radiographic criteria within 48 hours prior to randomization, with onset of criteria occurring after more than 2 days of hospitalization or within 7 days after discharge from a hospital for HABP; or at least 2 days after mechanical ventilation (for VABP)
• Has an adequate baseline (at or within 2 days of screening) lower respiratory tract specimen obtained for Gram stain and culture
• Has an infection known or thought to be, in the opinion of the investigator, 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 and long-term storage
• Males agree to use contraception as detailed in protocol from the time of providing informed consent through completion of the study and refrain from donating sperm during this period
• Females are not pregnant, not breastfeeding, and are either: a.) Not a woman of childbearing potential (WOCBP) OR b.) A WOCBP who agrees to follow the contraceptive guidance from the time of providing informed consent through completion of the study
• If a penicillin skin test is required by local clinical practice, the participant must have a negative skin test result for allergy to penicillin

You may not qualify if:

• 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 caused by Mycoplasma, Chlamydia, or Legionella, or of viral, fungal, or parasitic etiology
• Has HABP/VABP caused by an obstructive process, including lung cancer (or other malignancy metastatic to the lungs resulting in pulmonary obstruction) or other known obstruction
• Has a carcinoid tumor or carcinoid syndrome
• Has active immunosuppression
• Is expected to die during the 7- to 14-day treatment period, despite adequate antibiotic therapy
• Has a concurrent condition or infection that, in the investigator's judgment, would preclude evaluation of therapeutic response
• Has a history of serious allergy, hypersensitivity, or any serious reaction to any β-lactams or β-lactamase inhibitors
• Has a history of a seizure disorder which has required ongoing treatment with anticonvulsive therapy or prior treatment with anti-convulsive therapy within the last 3 years
• Is currently undergoing hemodialysis or peritoneal dialysis
• A WOCBP who has a positive urine pregnancy test at screening
• Has received effective antibacterial drug therapy with known coverage of pathogens that cause HABP/VABP for a continuous duration of more than 48 hours during the previous 72 hours
• Is anticipated to be treated with any of the prohibited medications during the course of study therapy
• Is currently participating in, or has participated in, any other clinical study involving the administration of investigational or experimental medication (not licensed by regulatory agencies) at the time of the presentation or during the previous 90 days prior to screening or is anticipated to participate in such a clinical study during the course of this trial

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (68)

Santa Casa de Misericordia de Belo Horizonte ( Site 0300)

Belo Horizonte, Minas Gerais, 30150-221, Brazil

Location

Hospital de Base de Sao Jose de Rio Preto ( Site 0301)

Sao Jose Do Rio Preto - SP, São Paulo, 15090-000, Brazil

Location

Beijing Chaoyang Hospital ( Site 0126)

Beijing, Beijing Municipality, 100020, China

Location

Peking University First Hospital ( Site 0131)

Beijing, Beijing Municipality, 100034, China

Location

Aero Space center hospital ( Site 0118)

Beijing, Beijing Municipality, 100049, China

Location

The Seventh Medical Center of PLA General Hospital-Intensive medicine ( Site 0157)

Beijing, Beijing Municipality, 100073, China

Location

Peking University Third Hospital ( Site 0115)

Beijing, Beijing Municipality, 100191, China

Location

Beijing Hospital ( Site 0127)

Beijing, Beijing Municipality, 100730, China

Location

The First Affiliated Hospital Of Fujian Medical University-Respiratory ( Site 0136)

Fuzhou, Fujian, 350005, China

Location

Zhongshan Hospital Affiliated to Xiamen University ( Site 0133)

Xiamen, Fujian, 361004, China

Location

Zhangzhou Municipal Hospital of Fujian Province-Neurosurgery Department ( Site 0150)

Zhangzhou, Fujian, 363000, China

Location

The First Affiliated Hospital ( Site 0100)

Guangzhou, Guangdong, 510080, China

Location

The First Affiliated Hospital of Guangzhou Medical University ( Site 0123)

Guangzhou, Guangdong, 510120, China

Location

Guangzhou First People's Hospital ( Site 0101)

Guangzhou, Guangdong, 510180, China

Location

Zhujiang Hospital of Southern Medical University ( Site 0148)

Guangzhou, Guangdong, 510280, China

Location

Southern Medical University Nanfang Hospital ( Site 0120)

Guangzhou, Guangdong, 510515, China

Location

Huizhou Municipal Central Hospital ( Site 0140)

Huizhou, Guangdong, China

Location

Shenzhen People s Hospital ( Site 0134)

Shenzhen, Guangdong, 518020, China

Location

The first people s hospital of Nanning ( Site 0138)

Nanning, Guangxi, 530022, China

Location

The first people s hospital of Nanning ( Site 0141)

Nanning, Guangxi, 530022, China

Location

Hainan General Hospital ( Site 0106)

Haikou, Hainan, 570311, China

Location

The First Affiliated Hospital of Zhengzhou University ( Site 0121)

Zhengzhou, Henan, 450052, China

Location

Shiyan City People's Hospital-Neurosurgery ( Site 0155)

Shiyan, Hubei, 442000, China

Location

Changsha Central Hospital ( Site 0119)

Changsha, Hunan, 410004, China

Location

Hunan Provincial People Hospital ( Site 0122)

Changsha, Hunan, 410005, China

Location

The First People's Hospital of Changzhou ( Site 0139)

Changzhou, Jiangsu, 213003, China

Location

First Huai'an Hospital Affiliated to Nanjing Medical University-Neurosurgery Department ( Site 0153)

Huai'an, Jiangsu, 223300, China

Location

First Hospital Affiliated to Suzhou University ( Site 0111)

Suzhou, Jiangsu, 215008, China

Location

Wuxi People's Hospital ( Site 0124)

Wuxi, Jiangsu, 214023, China

Location

Affiliated Hospital of Jiangsu University ( Site 0147)

Zhenjiang, Jiangsu, 212000, China

Location

Jiangxi Provincial People's Hospital ( Site 0129)

Nanchang, Jiangxi, 330006, China

Location

The First Affiliated Hospital of Nanchang University ( Site 0132)

Nanchang, Jiangxi, 330006, China

Location

The Second Affiliated Hospital of Nanchang University-Neurosurgery Department ( Site 0151)

Nanchang, Jiangxi, 330006, China

Location

The First Affiliated Hospital of China Medical University ( Site 0116)

Shenyang, Liaoning, 110001, China

Location

General Hospital of Ningxia Medical University ( Site 0135)

Yinchuan, Ningxia, 750004, China

Location

People's Hospital of Liaocheng City-Neurology ( Site 0154)

Liaocheng, Shandong, 252000, China

Location

Ruijin Hospital Shanghai Jiao Tong University School of Medicine ( Site 0104)

Shanghai, Shanghai Municipality, 200025, China

Location

Huadong Hospital Affiliated Fudan University ( Site 0103)

Shanghai, Shanghai Municipality, 200040, China

Location

Huashan Hospital of Fudan University ( Site 0105)

Shanghai, Shanghai Municipality, 200040, China

Location

Shanghai General Hospital ( Site 0125)

Shanghai, Shanghai Municipality, 200080, China

Location

Shanghai Pulmonary Hospital ( Site 0108)

Shanghai, Shanghai Municipality, 200443, China

Location

Tianjin Medical University General Hospital ( Site 0113)

Tianjin, Tianjin Municipality, 300052, China

Location

The First Affiliated Hospital.Zhejiang University ( Site 0102)

Hangzhou, Zhejiang, 310003, China

Location

Sir Run Run Shaw Hospital School of Medicine Zhejiang University ( Site 0110)

Hangzhou, Zhejiang, 310016, China

Location

People s Hospital of Lishui City ( Site 0137)

Lishui, Zhejiang, 323000, China

Location

Ningbo First Hospital-neurosurgery ( Site 0152)

Ningbo, Zhejiang, 315010, China

Location

The 2nd Affiliated Hospital of Wenzhou Medical University ( Site 0130)

Wenzhou, Zhejiang, 325000, China

Location

Hopital Roger Salengro du Lille ( Site 0601)

Lille, Nord, 59037, France

Location

CHU de Nantes - Hotel Dieu ( Site 0600)

Nantes, Pays de la Loire Region, 44093, France

Location

Hospices Civils de Lyon ( Site 0603)

Pierre-Bénite, Rhone, 69495, France

Location

Hopital Bicetre ( Site 0605)

Le Kremlin-Bicêtre, Val-de-Marne, 94270, France

Location

Hospital Civil de Guadalajara Fray Antonio Alcalde ( Site 0800)

Guadalajara, Jalisco, 44280, Mexico

Location

Hospital Civil Nuevo de Guadalajara Dr. Juan I. Menchaca ( Site 0804)

Guadalajara, Jalisco, 44340, Mexico

Location

Mary Johnston Hospital ( Site 0901)

Metro Manila, National Capital Region, 1012, Philippines

Location

Lung Center of the Philippines ( Site 0903)

Quezon City, National Capital Region, 1104, Philippines

Location

West Visayas State University Medical Center ( Site 0900)

Iloilo City, 5000, Philippines

Location

Spitalul Clinic Judetean de Urgenta Pius Branzeu ( Site 1103)

Timișoara, Timiș County, 300723, Romania

Location

Spitalul Clinic de Urgenta Bagdasar-Arseni ( Site 1101)

Bucharest, 041915, Romania

Location

First City Clinical Hospital n.a. E.E.Volosevich ( Site 1016)

Arkhangelsk, Arkhangelskaya oblast, 163001, Russia

Location

City Hospital #2 Severodvinsk ( Site 1017)

Severodvinsk, Arkhangelskaya oblast, 164500, Russia

Location

Research Institute of Emergency Medicine n.a. I.I.Dzhanelidze ( Site 1011)

Saint Petersburg, Sankt-Peterburg, 192242, Russia

Location

Clinical Hospital #122 L.G. Sokolova FMBA ( Site 1015)

Saint Petersburg, Sankt-Peterburg, 194291, Russia

Location

City Hospital #26 ( Site 1002)

Saint Petersburg, Sankt-Peterburg, 196247, Russia

Location

ME Dnipropetrovsk Clinical Joinder of Emergency Care of DRC ( Site 1304)

Dnipro, Dnipropetrovsk Oblast, 49006, Ukraine

Location

Ivano-Frankivsk regional clinical hospital ( Site 1301)

Ivano-Frankivsk, Ivano-Frankivsk Oblast, 76008, Ukraine

Location

City Clinical Hospital No13 of Kharkiv City Council ( Site 1303)

Kharkiv, Kharkivs’ka Oblast’, 61124, Ukraine

Location

Kiyv city municipal hospital 17 ( Site 1300)

Kiev, Kyivska Oblast, 01133, Ukraine

Location

Reg. Clin. Hospital ( Site 1306)

Poltava, Poltava Oblast, 36000, Ukraine

Location

Related Publications (1)

• Li J, Wei F, Xiang P, Tang Z, Ding L, Chen LF, Losada M, Iamboliyska Z, Sun F, Zhu M, Guo X, Du X, Chen C, Bruno C, Koseoglu S, Young K, Zhou M, Qu J. A phase III, randomized, controlled noninferiority trial to study the efficacy and safety of imipenem/cilastatin/relebactam (IMI/REL) vs piperacillin/tazobactam (PIP/TAZ) in patients with hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP). Int J Infect Dis. 2025 Apr;153:107357. doi: 10.1016/j.ijid.2024.107357. Epub 2024 Dec 12.

  PMID: 39674398 RESULT

MeSH Terms

Interventions

Linezolid

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Oxazolidinones; Oxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@msd.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2018
• First Posted: July 11, 2018
• Study Start: September 18, 2018
• Primary Completion: July 12, 2022
• Study Completion: July 12, 2022
• Last Updated: January 29, 2025
• Results First Posted: June 28, 2023

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share

Locations

FR (4); CN (45); PH (3); ME (2); RO (2); BR (2); RU (5); UA (5)