IMI/REL (MK-7655A) vs. PIP/TAZ in Treatment of Subjects with HABP/VABP.

• Register: EUCTR
• Last refreshed on: 16 December 2019
• Main ID: EUCTR2015-000246-34-DE
• Date of registration: 23/06/2015
• Prospective Registration: Yes
• Primary sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
• Public title: IMI/REL (MK-7655A) vs. PIP/TAZ in Treatment of Subjects with HABP/VABP.
• 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. - IMI/REL (MK-7655A) vs. PIP/TAZ in Treatment of Subjects with HABP/VABP.
• Date of first enrolment: 28/09/2015
• Target sample size: 536
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-000246-34
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Brazil, Bulgaria, Colombia, Croatia, Czech Republic, Estonia, France, Germany, Korea, Republic of, Latvia, Lithuania, Mexico, Philippines, Portugal, Romania, Russian Federation, Spain, United States

Contacts

• Name: Global Clinical Trials Operations
• Affiliation: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

• Name: Global Clinical Trials Operations
• Affiliation: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
1. be = 18 years of age on the day of signing informed consent.
2. require treatment with IV antibiotic therapy for hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP).
3. fulfill the clinical and radiographic criteria (detailed in the protocol) 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): Refer to protocol for defining clinical features.
4. have a baseline (at or within 48 hours of screening) lower respiratory tract specimen obtained for Gram stain and culture.
5. have an infection known or thought to be, in the opinion of the investigator, caused by microorganisms susceptible to the IV study therapy.
6. agree 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.
7. understand (or have a legal representative that understands) the study procedures, alternative treatments available, and risks involved with the study, and voluntarily agree to participate by giving written informed consent for the trial. The subject may also provide consent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research.
8. if male or female of childbearing potential, use appropriate contraception (refer to protocol for contraception guidance details).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 430
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 106

Exclusion criteria:
1.has a baseline lower respiratory tract specimen Gram stain that shows the presence of Gram-positive cocci only.
2. has confirmed or suspected community-acquired bacterial pneumonia (CABP).
3. has confirmed or suspected pneumonia of viral, fungal, or parasitic etiology.
4. 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.
5. has a carcinoid tumor or carcinoid syndrome.
6. has active immunosuppression, defined as either receiving immunosuppressive medications or having a medical condition associated with immunodeficiency.
7. is expected to survive < 72 hours.
8. has a concurrent condition or infection that, in the investigator’s judgment, would preclude evaluation of therapeutic response (e.g. active tuberculosis, cystic fibrosis, granulomatous disease, a disseminated fungal infection, invasive fungal pulmonary infection or endocarditis).
9. has received effective antibacterial drug therapy for the index infection of HABP/VABP for a continuous duration of more than 24 hours during the previous 72 hours.
10. a history of serious allergy, hypersensitivity (e.g., anaphylaxis), or any serious reaction to any of the following: any penicillin or ß-lactamase inhibitors.
11. is a female who is pregnant or is expecting to conceive (or is a male partner of a female who is expecting to conceive), is breastfeeding, or plans to breastfeed prior to completion of the study.
12. has a history of a seizure disorder which has required ongoing treatment with anti-convulsive therapy or prior treatment with anti-convulsive therapy within the last 3 years.
13. is anticipated to be treated with any of the following medications during the course of study therapy: refer to ptorocol for list on concomitant meds
14. has an estimated or actual creatinine clearance of < 15 mL/min at screening, based on the findings of local laboratory values.
15. is currently undergoing hemodialysis or peritoneal dialysis.
16. has a history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that, in the opinion of the investigator, might confound the results of the study, interfere with the subject’s participation for the full duration of the study, or pose additional risk in administering the study drugs to the subject.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

Treatment for hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP).

Intervention(s)

Product Name: imipenem/cilastatin/relebactam
Product Code: MK-7655A
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: IMIPENEM
CAS Number: 64221-86-9
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-
INN or Proposed INN: Relebactam
Other descriptive name: MK-7655
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 250-
INN or Proposed INN: Cilastatin
CAS Number: 82009-34-5
Other descriptive name: CILASTATIN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-

Trade Name: Piperacillin/Tazobactam-Teva
Product Name: piperallicin/tazobactam
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Tazobactam
Other descriptive name: TAZOBACTAM
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-
INN or Proposed INN: Piperallicin
Other descriptive name: PIPERACILLIN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 4000-

Trade Name: Piperacillin/Tazobactam-Accord
Product Name: piperallicin/tazobactam
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Tazobactam
Other descriptive name: TAZOBACTAM
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-
INN

Primary Outcome(s)

Main Objective: To determine the incidence rate of all-cause mortality through Day 28 post-randomization associated with treatment with IMI/REL compared to treatment with PIP/TAZ in subjects diagnosed with HABP/VABP in the modified intention-to-treat (MITT) population.

Secondary Objective: To evaluate the efficacy of IMI/REL versus PIP/TAZ with respect to clinical response at the early follow-up (EFU) visit 7 to 14 days after the end of therapy (EOT) for subjects diagnosed with HABP/VABP in the MITT population.

Primary end point(s): Survival/All-cause Mortality: Survival status (i.e., whether the subject is alive or dead) through Day 28 post-randomization and EFU visits will be evaluated for all subjects in support of the primary and key secondary objectives, respectively.

Timepoint(s) of evaluation of this end point: 1. Survival/All-cause Mortality: Day 28.

Secondary Outcome(s)

Secondary end point(s): Clinical response will be assessed for all subjects based on evaluation by the investigator at the OTX1, OTX2, OTX3 (if applicable), EOT, EFU, and Day 28 post-randomization visits. Microbiological response will be evaluated separately for each lower respiratory tract pathogen isolated in the baseline culture (i.e., by-pathogen). The by-pathogen response rating determined by the investigator will be assessed based on local laboratory results.

Timepoint(s) of evaluation of this end point: 1. Clinical response: OTX1, OTX2, OTX3 (if applicable), EOT, EFU, and Day 28 post-randomization visits.
2. Microbiological response: EOT & EFU.

Secondary ID(s)

7655A-014

Source(s) of Monetary Support

Merck Sharp & Dohme Corp.

Ethics review

Status: Approved
Approval date:
Contact: