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

Sponsor

Merck Sharp & Dohme LLC (Industry)

Overall Status

Completed

CT.gov ID

NCT03583333

Collaborator

(none)

274

Enrollment

Locations

Arms

45.8

Actual Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will evaluate the efficacy and safety of imipenem/cilastatin/relebactam (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.

Condition or Disease	Intervention/Treatment	Phase
Hospital-Acquired Bacterial Pneumonia Ventilator-Associated Bacterial Pneumonia	Drug: IMI/REL FDC Drug: PIP/TAZ FDC Drug: Linezolid	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

274 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Multi-national Phase 3, 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

Actual Study Start Date :

Sep 18, 2018

Actual Primary Completion Date :

Jul 12, 2022

Actual Study Completion Date :

Jul 12, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: IMI/REL FDC Imipenem/cilastatin/relebactam (IMI/REL) administered intravenously (IV) as a fixed-dose combination (FDC) at a dosage of 500 mg IMI/250 mg REL/500 mg Cilastatin, 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 500 mg Imipenem, 500 mg Cilastatin and 250 mg Relebactam powder FDC provided in a single vial Other Names: MK-7655A Drug: Linezolid Open-label 600 mg Linezolid
Active Comparator: PIP/TAZ FDC 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 4000 mg Piperacillin and 500 mg Tazobactam powder FDC provided in a single vial Drug: Linezolid Open-label 600 mg Linezolid

Arm

Intervention/Treatment

Experimental: IMI/REL FDC

Imipenem/cilastatin/relebactam (IMI/REL) administered intravenously (IV) as a fixed-dose combination (FDC) at a dosage of 500 mg IMI/250 mg REL/500 mg Cilastatin, 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

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

Other Names:

MK-7655A

Drug: Linezolid

Open-label 600 mg Linezolid

Active Comparator: PIP/TAZ FDC

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

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

Drug: Linezolid

Open-label 600 mg Linezolid

Outcome Measures

Primary Outcome Measures

All-cause mortality [Up to Day 28]
Percentage of participants with all-cause mortality through Day 28

Secondary Outcome Measures

Favorable clinical response at end of treatment (EOT) visit [From treatment Day 7 up to Day 15]
Percentage of participants achieving a favorable clinical response at EOT visit.
Favorable clinical response at early follow-up (EFU) visit [7-14 days post-EOT (up to Day 28)]
Percentage of participants achieving a favorable clinical response at EFU visit
Favorable microbiological response at EFU visit. [7-14 days post-EOT (up to Day 28)]
Percentage of participants achieving a favorable microbiological response at EFU visit.
Favorable microbiological response at EOT visit. [From treatment Day 7 up to Day 15]
Percentage of participants achieving a favorable microbiological response at EOT visit.
Adverse Events [Up to Day 31]
Number of participants experiencing adverse events
Discontinuations due to adverse events [Up to Day 14]
Number of participants discontinuing study drug due to adverse events

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

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 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
Has previously participated in this study at any time

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Santa Casa de Misericordia de Belo Horizonte ( Site 0300)	Belo Horizonte	Minas Gerais	Brazil	30150-221
2	Hospital de Base de Sao Jose de Rio Preto ( Site 0301)	Sao Jose Do Rio Preto - SP	Sao Paulo	Brazil	15090-000
3	Beijing Chaoyang Hospital ( Site 0126)	Beijing	Beijing	China	100020
4	Peking University First Hospital ( Site 0131)	Beijing	Beijing	China	100034
5	Aero Space center hospital ( Site 0118)	Beijing	Beijing	China	100049
6	The Seventh Medical Center of PLA General Hospital-Intensive medicine ( Site 0157)	Beijing	Beijing	China	100073
7	Peking University Third Hospital ( Site 0115)	Beijing	Beijing	China	100191
8	Beijing Hospital ( Site 0127)	Beijing	Beijing	China	100730
9	The First Affiliated Hospital Of Fujian Medical University-Respiratory ( Site 0136)	Fuzhou	Fujian	China	350005
10	Zhongshan Hospital Affiliated to Xiamen University ( Site 0133)	Xiamen	Fujian	China	361004
11	Zhangzhou Municipal Hospital of Fujian Province-Neurosurgery Department ( Site 0150)	Zhangzhou	Fujian	China	363000
12	The First Affiliated Hospital ( Site 0100)	GuangZhou	Guangdong	China	510080
13	The First Affiliated Hospital of Guangzhou Medical University ( Site 0123)	Guangzhou	Guangdong	China	510120
14	Guangzhou First People's Hospital ( Site 0101)	Guangzhou	Guangdong	China	510180
15	Zhujiang Hospital of Southern Medical University ( Site 0148)	Guangzhou	Guangdong	China	510280
16	Southern Medical University Nanfang Hospital ( Site 0120)	Guangzhou	Guangdong	China	510515
17	Huizhou Municipal Central Hospital ( Site 0140)	Huizhou	Guangdong	China
18	Shenzhen People s Hospital ( Site 0134)	Shenzhen	Guangdong	China	518020
19	The first people s hospital of Nanning ( Site 0138)	Nanning	Guangxi	China	530022
20	The first people s hospital of Nanning ( Site 0141)	Nanning	Guangxi	China	530022
21	Hainan General Hospital ( Site 0106)	Haikou	Hainan	China	570311
22	The First Affiliated Hospital of Zhengzhou University ( Site 0121)	Zhengzhou	Henan	China	450052
23	Shiyan City People's Hospital-Neurosurgery ( Site 0155)	Shiyan	Hubei	China	442000
24	Changsha Central Hospital ( Site 0119)	Changsha	Hunan	China	410004
25	Hunan Provincial People Hospital ( Site 0122)	Changsha	Hunan	China	410005
26	The First People's Hospital of Changzhou ( Site 0139)	Changzhou	Jiangsu	China	213003
27	First Huai'an Hospital Affiliated to Nanjing Medical University-Neurosurgery Department ( Site 0153)	Huai'an	Jiangsu	China	223300
28	First Hospital Affiliated to Suzhou University ( Site 0111)	Suzhou	Jiangsu	China	215008
29	Wuxi People's Hospital ( Site 0124)	Wuxi	Jiangsu	China	214023
30	Affiliated Hospital of Jiangsu University ( Site 0147)	Zhenjiang	Jiangsu	China	212000
31	Jiangxi Provincial People's Hospital ( Site 0129)	Nanchang	Jiangxi	China	330006
32	The First Affiliated Hospital of Nanchang University ( Site 0132)	Nanchang	Jiangxi	China	330006
33	The Second Affiliated Hospital of Nanchang University-Neurosurgery Department ( Site 0151)	Nanchang	Jiangxi	China	330006
34	The First Affiliated Hospital of China Medical University ( Site 0116)	Shenyang	Liaoning	China	110001
35	General Hospital of Ningxia Medical University ( Site 0135)	Yinchuan	Ningxia	China	750004
36	People's Hospital of Liaocheng City-Neurology ( Site 0154)	Liaocheng	Shandong	China	252000
37	Ruijin Hospital Shanghai Jiao Tong University School of Medicine ( Site 0104)	Shanghai	Shanghai	China	200025
38	Huadong Hospital Affiliated Fudan University ( Site 0103)	Shanghai	Shanghai	China	200040
39	Huashan Hospital of Fudan University ( Site 0105)	Shanghai	Shanghai	China	200040
40	Shanghai General Hospital ( Site 0125)	Shanghai	Shanghai	China	200080
41	Shanghai Pulmonary Hospital ( Site 0108)	Shanghai	Shanghai	China	200443
42	Tianjin Medical University General Hospital ( Site 0113)	Tianjin	Tianjin	China	300052
43	The First Affiliated Hospital.Zhejiang University ( Site 0102)	Hangzhou	Zhejiang	China	310003
44	Sir Run Run Shaw Hospital School of Medicine Zhejiang University ( Site 0110)	Hangzhou	Zhejiang	China	310016
45	People s Hospital of Lishui City ( Site 0137)	Lishui	Zhejiang	China	323000
46	Ningbo First Hospital-neurosurgery ( Site 0152)	Ningbo	Zhejiang	China	315010
47	The 2nd Affiliated Hospital of Wenzhou Medical University ( Site 0130)	Wenzhou	Zhejiang	China	325000
48	Hopital Roger Salengro du Lille ( Site 0601)	Lille	Nord	France	59037
49	CHU de Nantes - Hotel Dieu ( Site 0600)	Nantes	Pays-de-la-Loire	France	44093
50	Hospices Civils de Lyon ( Site 0603)	Pierre Benite	Rhone	France	69495
51	Hopital Bicetre ( Site 0605)	Le Kremlin-Bicetre	Val-de-Marne	France	94270
52	Hospital Civil de Guadalajara Fray Antonio Alcalde ( Site 0800)	Guadalajara	Jalisco	Mexico	44280
53	Hospital Civil Nuevo de Guadalajara Dr. Juan I. Menchaca ( Site 0804)	Guadalajara	Jalisco	Mexico	44340
54	Mary Johnston Hospital ( Site 0901)	Metro Manila	National Capital Region	Philippines	1012
55	Lung Center of the Philippines ( Site 0903)	Quezon	National Capital Region	Philippines	1104
56	West Visayas State University Medical Center ( Site 0900)	Iloilo		Philippines	5000
57	Spitalul Clinic Judetean de Urgenta Pius Branzeu ( Site 1103)	Timisoara	Timis	Romania	300723
58	Spitalul Clinic de Urgenta Bagdasar-Arseni ( Site 1101)	Bucuresti		Romania	041915
59	First City Clinical Hospital n.a. E.E.Volosevich ( Site 1016)	Arkhangelsk	Arkhangel Skaya Oblast	Russian Federation	163001
60	City Hospital #2 Severodvinsk ( Site 1017)	Severodvinsk	Arkhangel Skaya Oblast	Russian Federation	164500
61	Research Institute of Emergency Medicine n.a. I.I.Dzhanelidze ( Site 1011)	Saint Petersburg	Sankt-Peterburg	Russian Federation	192242
62	Clinical Hospital #122 L.G. Sokolova FMBA ( Site 1015)	Saint Petersburg	Sankt-Peterburg	Russian Federation	194291
63	City Hospital #26 ( Site 1002)	Saint-Petersburg	Sankt-Peterburg	Russian Federation	196247
64	ME Dnipropetrovsk Clinical Joinder of Emergency Care of DRC ( Site 1304)	Dnipro	Dnipropetrovska Oblast	Ukraine	49006
65	Ivano-Frankivsk regional clinical hospital ( Site 1301)	Ivano-Frankivsk	Ivano-Frankivska Oblast	Ukraine	76008
66	City Clinical Hospital No13 of Kharkiv City Council ( Site 1303)	Kharkiv	Kharkivska Oblast	Ukraine	61124
67	Kiyv city municipal hospital 17 ( Site 1300)	Kiev	Kyivska Oblast	Ukraine	01133
68	Reg. Clin. Hospital ( Site 1306)	Poltava	Poltavska Oblast	Ukraine	36000

Sponsors and Collaborators

Merck Sharp & Dohme LLC

Investigators

Study Director: Medical Director, Merck Sharp & Dohme LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Merck Sharp & Dohme LLC

ClinicalTrials.gov Identifier:

NCT03583333

Other Study ID Numbers:

7655A-016
MK-7655A-016
PHRR190814-002177
2018-003202-82

First Posted:

Jul 11, 2018

Last Update Posted:

Jul 20, 2022

Last Verified:

Jul 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Yes

Additional relevant MeSH terms:

Pneumonia

Pneumonia, Bacterial

Linezolid

Study Results

No Results Posted as of Jul 20, 2022