Ventilator-Associated Bacterial Pneumonia Clinical Trial
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
| Verified date | June 2023 |
| Source | Merck Sharp & Dohme LLC |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 274 |
| Est. completion date | July 12, 2022 |
| Est. primary completion date | July 12, 2022 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 90 Years |
| Eligibility | 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 ß-lactams or ß-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 |
| Country | Name | City | State |
|---|---|---|---|
| Brazil | Santa Casa de Misericordia de Belo Horizonte ( Site 0300) | Belo Horizonte | Minas Gerais |
| Brazil | Hospital de Base de Sao Jose de Rio Preto ( Site 0301) | Sao Jose Do Rio Preto - SP | Sao Paulo |
| China | Aero Space center hospital ( Site 0118) | Beijing | Beijing |
| China | Beijing Chaoyang Hospital ( Site 0126) | Beijing | Beijing |
| China | Beijing Hospital ( Site 0127) | Beijing | Beijing |
| China | Peking University First Hospital ( Site 0131) | Beijing | Beijing |
| China | Peking University Third Hospital ( Site 0115) | Beijing | Beijing |
| China | The Seventh Medical Center of PLA General Hospital-Intensive medicine ( Site 0157) | Beijing | Beijing |
| China | Changsha Central Hospital ( Site 0119) | Changsha | Hunan |
| China | Hunan Provincial People Hospital ( Site 0122) | Changsha | Hunan |
| China | The First People's Hospital of Changzhou ( Site 0139) | Changzhou | Jiangsu |
| China | The First Affiliated Hospital Of Fujian Medical University-Respiratory ( Site 0136) | Fuzhou | Fujian |
| China | Guangzhou First People's Hospital ( Site 0101) | Guangzhou | Guangdong |
| China | Southern Medical University Nanfang Hospital ( Site 0120) | Guangzhou | Guangdong |
| China | The First Affiliated Hospital ( Site 0100) | GuangZhou | Guangdong |
| China | The First Affiliated Hospital of Guangzhou Medical University ( Site 0123) | Guangzhou | Guangdong |
| China | Zhujiang Hospital of Southern Medical University ( Site 0148) | Guangzhou | Guangdong |
| China | Hainan General Hospital ( Site 0106) | Haikou | Hainan |
| China | Sir Run Run Shaw Hospital School of Medicine Zhejiang University ( Site 0110) | Hangzhou | Zhejiang |
| China | The First Affiliated Hospital.Zhejiang University ( Site 0102) | Hangzhou | Zhejiang |
| China | First Huai'an Hospital Affiliated to Nanjing Medical University-Neurosurgery Department ( Site 0153) | Huai'an | Jiangsu |
| China | Huizhou Municipal Central Hospital ( Site 0140) | Huizhou | Guangdong |
| China | People's Hospital of Liaocheng City-Neurology ( Site 0154) | Liaocheng | Shandong |
| China | People s Hospital of Lishui City ( Site 0137) | Lishui | Zhejiang |
| China | Jiangxi Provincial People's Hospital ( Site 0129) | Nanchang | Jiangxi |
| China | The First Affiliated Hospital of Nanchang University ( Site 0132) | Nanchang | Jiangxi |
| China | The Second Affiliated Hospital of Nanchang University-Neurosurgery Department ( Site 0151) | Nanchang | Jiangxi |
| China | The first people s hospital of Nanning ( Site 0138) | Nanning | Guangxi |
| China | The first people s hospital of Nanning ( Site 0141) | Nanning | Guangxi |
| China | Ningbo First Hospital-neurosurgery ( Site 0152) | Ningbo | Zhejiang |
| China | Huadong Hospital Affiliated Fudan University ( Site 0103) | Shanghai | Shanghai |
| China | Huashan Hospital of Fudan University ( Site 0105) | Shanghai | Shanghai |
| China | Ruijin Hospital Shanghai Jiao Tong University School of Medicine ( Site 0104) | Shanghai | Shanghai |
| China | Shanghai General Hospital ( Site 0125) | Shanghai | Shanghai |
| China | Shanghai Pulmonary Hospital ( Site 0108) | Shanghai | Shanghai |
| China | The First Affiliated Hospital of China Medical University ( Site 0116) | Shenyang | Liaoning |
| China | Shenzhen People s Hospital ( Site 0134) | Shenzhen | Guangdong |
| China | Shiyan City People's Hospital-Neurosurgery ( Site 0155) | Shiyan | Hubei |
| China | First Hospital Affiliated to Suzhou University ( Site 0111) | Suzhou | Jiangsu |
| China | Tianjin Medical University General Hospital ( Site 0113) | Tianjin | Tianjin |
| China | The 2nd Affiliated Hospital of Wenzhou Medical University ( Site 0130) | Wenzhou | Zhejiang |
| China | Wuxi People's Hospital ( Site 0124) | Wuxi | Jiangsu |
| China | Zhongshan Hospital Affiliated to Xiamen University ( Site 0133) | Xiamen | Fujian |
| China | General Hospital of Ningxia Medical University ( Site 0135) | Yinchuan | Ningxia |
| China | Zhangzhou Municipal Hospital of Fujian Province-Neurosurgery Department ( Site 0150) | Zhangzhou | Fujian |
| China | The First Affiliated Hospital of Zhengzhou University ( Site 0121) | Zhengzhou | Henan |
| China | Affiliated Hospital of Jiangsu University ( Site 0147) | Zhenjiang | Jiangsu |
| France | Hopital Bicetre ( Site 0605) | Le Kremlin-Bicetre | Val-de-Marne |
| France | Hopital Roger Salengro du Lille ( Site 0601) | Lille | Nord |
| France | CHU de Nantes - Hotel Dieu ( Site 0600) | Nantes | Pays-de-la-Loire |
| France | Hospices Civils de Lyon ( Site 0603) | Pierre Benite | Rhone |
| Mexico | Hospital Civil de Guadalajara Fray Antonio Alcalde ( Site 0800) | Guadalajara | Jalisco |
| Mexico | Hospital Civil Nuevo de Guadalajara Dr. Juan I. Menchaca ( Site 0804) | Guadalajara | Jalisco |
| Philippines | West Visayas State University Medical Center ( Site 0900) | Iloilo | |
| Philippines | Mary Johnston Hospital ( Site 0901) | Metro Manila | National Capital Region |
| Philippines | Lung Center of the Philippines ( Site 0903) | Quezon | National Capital Region |
| Romania | Spitalul Clinic de Urgenta Bagdasar-Arseni ( Site 1101) | Bucuresti | |
| Romania | Spitalul Clinic Judetean de Urgenta Pius Branzeu ( Site 1103) | Timisoara | Timis |
| Russian Federation | First City Clinical Hospital n.a. E.E.Volosevich ( Site 1016) | Arkhangelsk | Arkhangel Skaya Oblast |
| Russian Federation | Clinical Hospital #122 L.G. Sokolova FMBA ( Site 1015) | Saint Petersburg | Sankt-Peterburg |
| Russian Federation | Research Institute of Emergency Medicine n.a. I.I.Dzhanelidze ( Site 1011) | Saint Petersburg | Sankt-Peterburg |
| Russian Federation | City Hospital #26 ( Site 1002) | Saint-Petersburg | Sankt-Peterburg |
| Russian Federation | City Hospital #2 Severodvinsk ( Site 1017) | Severodvinsk | Arkhangel Skaya Oblast |
| Ukraine | ME Dnipropetrovsk Clinical Joinder of Emergency Care of DRC ( Site 1304) | Dnipro | Dnipropetrovska Oblast |
| Ukraine | Ivano-Frankivsk regional clinical hospital ( Site 1301) | Ivano-Frankivsk | Ivano-Frankivska Oblast |
| Ukraine | City Clinical Hospital No13 of Kharkiv City Council ( Site 1303) | Kharkiv | Kharkivska Oblast |
| Ukraine | Kiyv city municipal hospital 17 ( Site 1300) | Kiev | Kyivska Oblast |
| Ukraine | Reg. Clin. Hospital ( Site 1306) | Poltava | Poltavska Oblast |
| Lead Sponsor | Collaborator |
|---|---|
| Merck Sharp & Dohme LLC |
Brazil, China, France, Mexico, Philippines, Romania, Russian Federation, Ukraine,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 | Percentage of Participants Achieving a Favorable Clinical Response at Early Follow-up (EFU) Visit in the MITT Population | Clinical response was defined as "Sustained cure" (All pretherapy signs and symptoms of the index infection have resolved or returned to preinfection status with no evidence of resurgence AND no additional antibiotic therapy was required for the index infection) or "Cure" (All pretherapy signs and symptoms of the index infection have resolved or returned to preinfection status AND no additional antibiotic therapy was required for the index infection). The percentage of participants achieving a favorable clinical response at EFU visit in the MITT population is presented. | Up to approximately 27 days | |
| Secondary | Percentage of Participants Achieving a Favorable Clinical Response at EFU Visit in the Clinically Evaluable (CE) Population | Clinical response was defined as "Sustained cure" (All pretherapy signs and symptoms of the index infection have resolved or returned to preinfection status with no evidence of resurgence) AND no additional antibiotic therapy was required for the index infection or "Cure" (All pretherapy signs and symptoms of the index infection have resolved or returned to preinfection status) AND no additional antibiotic therapy was required for the index infection. The percentage of participants achieving a favorable clinical response at EFU visit in the CE population is presented. | Up to approximately 27 days | |
| Secondary | Percentage of Participants Achieving a Favorable Clinical Response at End of Therapy (EOT) Visit in the MITT Population | Clinical response was defined as "Improved" (The majority of pre-therapy signs and symptoms of the index infection have improved or resolved or returned to "pre-infection status" AND no additional antibiotic therapy was required) or "Cure" (All pretherapy signs and symptoms of the index infection have resolved or returned to preinfection status AND no additional antibiotic therapy was required for the index infection). The percentage of participants achieving a favorable clinical response at EOT visit in the MITT population is presented. | Up to approximately 14 days | |
| Secondary | Percentage of Participants Achieving a Favorable Clinical Response at EOT Visit in the Clinically Evaluable (CE) Population | Clinical response was defined as "Improved" (The majority of pre-therapy signs and symptoms of the index infection have improved or resolved or returned to "pre-infection status" AND no additional antibiotic therapy is required) or "Cure" (All pretherapy signs and symptoms of the index infection have resolved or returned to preinfection status) AND no additional antibiotic therapy is required for the index infection. The percentage of participants achieving a favorable clinical response at End of Treatment (EOT) visit in the CE population is presented. | Up to approximately 14 days | |
| Secondary | Percentage of Participants Achieving a Favorable Microbiological Response at EOT Visit in Microbiological Modified Intent-To-Treat Population (mMITT) Population | Favorable overall microbiological response rates were defined as "eradication" (A lower respiratory tract culture taken at the EOT visit showed eradication of the pathogen found at study entry) OR "presumed eradication" (No specimen taken because participant was deemed clinically cured or improved) of the baseline pathogen. The percentage of participants achieving a favorable microbiological response at EOT visit in the mMITT population is presented. | Up to approximately 14 days | |
| Secondary | Percentage of Participants Achieving a Favorable Microbiological Response at EFU Visit in Microbiological-evaluable (ME) Population. | A favorable by-pathogen microbiological response at EFU visit required "eradication" (A lower respiratory tract culture taken at the EFU visit showed eradication of the pathogen found at study entry) or "presumed eradication" (No specimen taken because participant was deemed clinically cured or improved) of the baseline pathogen. The percentage of participants achieving a favorable microbiological response at EFU visit in the ME population is presented. | Up to approximately 27 days | |
| Secondary | Percentage of Participants Achieving a Favorable Microbiological Response at EOT Visit in the ME Population | Favorable overall microbiological response rates was defined as "eradication" (A lower respiratory tract culture taken at the EOT visit showed eradication of the pathogen found at study entry) OR "presumed eradication" (No specimen taken because participant was deemed clinically cured or improved) of the baseline pathogen. The percentage of participants achieving a favorable microbiological response at End of Treatment (EOT) visit in the ME population is presented. | Up to approximately 14 days | |
| Secondary | Percentage of Participants Experiencing Adverse Events (AEs) | An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The percentage of participants experiencing an AE was reported for each arm. | Up to approximately 98 days | |
| Secondary | Percentage of Participants Discontinuing Study Drug Due to AEs | An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The percentage of participants that discontinued study therapy due to an AE was reported for each arm. | Up to approximately 14 days |
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