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| ID | Type | Description | Link |
|---|---|---|---|
| MK-7655A-016 | Other Identifier | MSD Protocol Number | |
| PHRR190814-002177 | Registry Identifier | PHRR | |
| 2018-003202-82 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| IMI/REL FDC | Drug | 500 mg Imipenem, 500 mg Cilastatin and 250 mg Relebactam powder FDC provided in a single vial |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Santa Casa de Misericordia de Belo Horizonte ( Site 0300) | Belo Horizonte | Minas Gerais | 30150-221 | Brazil | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39674398 | Result | 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. |
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Participants were randomized 1:1 to receive either FDC of imipenem/cilastatin (IMI) and relebactam (REL) [IMI/REL, MK-7655A], or piperacillin/tazobactam (PIP/TAZ).
This study was conducted at 54 centers in 8 countries.
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| ID | Title | Description |
|---|---|---|
| FG000 | IMI/REL FDC | Imipenem/cilastatin/relebactam (IMI/REL) was 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 were treated empirically with 600 mg open-label linezolid administered IV every 12 hours until methicillin-resistant Staphylococcus aureus (MRSA) was ruled out. Participants with confirmed MRSA infection continued to receive 600 mg linezolid every 12 hours for a minimum of 7 days, up to 14 days total. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 11, 2020 |
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| PIP/TAZ FDC | Drug | 4000 mg Piperacillin and 500 mg Tazobactam powder FDC provided in a single vial |
|
| Linezolid | Drug | Open-label 600 mg Linezolid |
|
| Up to approximately 27 days |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| Hospital de Base de Sao Jose de Rio Preto ( Site 0301) |
| Sao Jose Do Rio Preto - SP |
| São Paulo |
| 15090-000 |
| Brazil |
| Beijing Chaoyang Hospital ( Site 0126) | Beijing | Beijing Municipality | 100020 | China |
| Peking University First Hospital ( Site 0131) | Beijing | Beijing Municipality | 100034 | China |
| Aero Space center hospital ( Site 0118) | Beijing | Beijing Municipality | 100049 | China |
| The Seventh Medical Center of PLA General Hospital-Intensive medicine ( Site 0157) | Beijing | Beijing Municipality | 100073 | China |
| Peking University Third Hospital ( Site 0115) | Beijing | Beijing Municipality | 100191 | China |
| Beijing Hospital ( Site 0127) | Beijing | Beijing Municipality | 100730 | China |
| The First Affiliated Hospital Of Fujian Medical University-Respiratory ( Site 0136) | Fuzhou | Fujian | 350005 | China |
| Zhongshan Hospital Affiliated to Xiamen University ( Site 0133) | Xiamen | Fujian | 361004 | China |
| Zhangzhou Municipal Hospital of Fujian Province-Neurosurgery Department ( Site 0150) | Zhangzhou | Fujian | 363000 | China |
| The First Affiliated Hospital ( Site 0100) | Guangzhou | Guangdong | 510080 | China |
| The First Affiliated Hospital of Guangzhou Medical University ( Site 0123) | Guangzhou | Guangdong | 510120 | China |
| Guangzhou First People's Hospital ( Site 0101) | Guangzhou | Guangdong | 510180 | China |
| Zhujiang Hospital of Southern Medical University ( Site 0148) | Guangzhou | Guangdong | 510280 | China |
| Southern Medical University Nanfang Hospital ( Site 0120) | Guangzhou | Guangdong | 510515 | China |
| Huizhou Municipal Central Hospital ( Site 0140) | Huizhou | Guangdong | China |
| Shenzhen People s Hospital ( Site 0134) | Shenzhen | Guangdong | 518020 | China |
| The first people s hospital of Nanning ( Site 0138) | Nanning | Guangxi | 530022 | China |
| The first people s hospital of Nanning ( Site 0141) | Nanning | Guangxi | 530022 | China |
| Hainan General Hospital ( Site 0106) | Haikou | Hainan | 570311 | China |
| The First Affiliated Hospital of Zhengzhou University ( Site 0121) | Zhengzhou | Henan | 450052 | China |
| Shiyan City People's Hospital-Neurosurgery ( Site 0155) | Shiyan | Hubei | 442000 | China |
| Changsha Central Hospital ( Site 0119) | Changsha | Hunan | 410004 | China |
| Hunan Provincial People Hospital ( Site 0122) | Changsha | Hunan | 410005 | China |
| The First People's Hospital of Changzhou ( Site 0139) | Changzhou | Jiangsu | 213003 | China |
| First Huai'an Hospital Affiliated to Nanjing Medical University-Neurosurgery Department ( Site 0153) | Huai'an | Jiangsu | 223300 | China |
| First Hospital Affiliated to Suzhou University ( Site 0111) | Suzhou | Jiangsu | 215008 | China |
| Wuxi People's Hospital ( Site 0124) | Wuxi | Jiangsu | 214023 | China |
| Affiliated Hospital of Jiangsu University ( Site 0147) | Zhenjiang | Jiangsu | 212000 | China |
| Jiangxi Provincial People's Hospital ( Site 0129) | Nanchang | Jiangxi | 330006 | China |
| The First Affiliated Hospital of Nanchang University ( Site 0132) | Nanchang | Jiangxi | 330006 | China |
| The Second Affiliated Hospital of Nanchang University-Neurosurgery Department ( Site 0151) | Nanchang | Jiangxi | 330006 | China |
| The First Affiliated Hospital of China Medical University ( Site 0116) | Shenyang | Liaoning | 110001 | China |
| General Hospital of Ningxia Medical University ( Site 0135) | Yinchuan | Ningxia | 750004 | China |
| People's Hospital of Liaocheng City-Neurology ( Site 0154) | Liaocheng | Shandong | 252000 | China |
| Ruijin Hospital Shanghai Jiao Tong University School of Medicine ( Site 0104) | Shanghai | Shanghai Municipality | 200025 | China |
| Huadong Hospital Affiliated Fudan University ( Site 0103) | Shanghai | Shanghai Municipality | 200040 | China |
| Huashan Hospital of Fudan University ( Site 0105) | Shanghai | Shanghai Municipality | 200040 | China |
| Shanghai General Hospital ( Site 0125) | Shanghai | Shanghai Municipality | 200080 | China |
| Shanghai Pulmonary Hospital ( Site 0108) | Shanghai | Shanghai Municipality | 200443 | China |
| Tianjin Medical University General Hospital ( Site 0113) | Tianjin | Tianjin Municipality | 300052 | China |
| The First Affiliated Hospital.Zhejiang University ( Site 0102) | Hangzhou | Zhejiang | 310003 | China |
| Sir Run Run Shaw Hospital School of Medicine Zhejiang University ( Site 0110) | Hangzhou | Zhejiang | 310016 | China |
| People s Hospital of Lishui City ( Site 0137) | Lishui | Zhejiang | 323000 | China |
| Ningbo First Hospital-neurosurgery ( Site 0152) | Ningbo | Zhejiang | 315010 | China |
| The 2nd Affiliated Hospital of Wenzhou Medical University ( Site 0130) | Wenzhou | Zhejiang | 325000 | China |
| Hopital Roger Salengro du Lille ( Site 0601) | Lille | Nord | 59037 | France |
| CHU de Nantes - Hotel Dieu ( Site 0600) | Nantes | Pays de la Loire Region | 44093 | France |
| Hospices Civils de Lyon ( Site 0603) | Pierre-Bénite | Rhone | 69495 | France |
| Hopital Bicetre ( Site 0605) | Le Kremlin-Bicêtre | Val-de-Marne | 94270 | France |
| Hospital Civil de Guadalajara Fray Antonio Alcalde ( Site 0800) | Guadalajara | Jalisco | 44280 | Mexico |
| Hospital Civil Nuevo de Guadalajara Dr. Juan I. Menchaca ( Site 0804) | Guadalajara | Jalisco | 44340 | Mexico |
| Mary Johnston Hospital ( Site 0901) | Metro Manila | National Capital Region | 1012 | Philippines |
| Lung Center of the Philippines ( Site 0903) | Quezon City | National Capital Region | 1104 | Philippines |
| West Visayas State University Medical Center ( Site 0900) | Iloilo City | 5000 | Philippines |
| Spitalul Clinic Judetean de Urgenta Pius Branzeu ( Site 1103) | Timișoara | Timiș County | 300723 | Romania |
| Spitalul Clinic de Urgenta Bagdasar-Arseni ( Site 1101) | Bucharest | 041915 | Romania |
| First City Clinical Hospital n.a. E.E.Volosevich ( Site 1016) | Arkhangelsk | Arkhangelskaya oblast | 163001 | Russia |
| City Hospital #2 Severodvinsk ( Site 1017) | Severodvinsk | Arkhangelskaya oblast | 164500 | Russia |
| Research Institute of Emergency Medicine n.a. I.I.Dzhanelidze ( Site 1011) | Saint Petersburg | Sankt-Peterburg | 192242 | Russia |
| Clinical Hospital #122 L.G. Sokolova FMBA ( Site 1015) | Saint Petersburg | Sankt-Peterburg | 194291 | Russia |
| City Hospital #26 ( Site 1002) | Saint Petersburg | Sankt-Peterburg | 196247 | Russia |
| ME Dnipropetrovsk Clinical Joinder of Emergency Care of DRC ( Site 1304) | Dnipro | Dnipropetrovsk Oblast | 49006 | Ukraine |
| Ivano-Frankivsk regional clinical hospital ( Site 1301) | Ivano-Frankivsk | Ivano-Frankivsk Oblast | 76008 | Ukraine |
| City Clinical Hospital No13 of Kharkiv City Council ( Site 1303) | Kharkiv | Kharkiv Oblast | 61124 | Ukraine |
| Kiyv city municipal hospital 17 ( Site 1300) | Kiev | Kyivska Oblast | 01133 | Ukraine |
| Reg. Clin. Hospital ( Site 1306) | Poltava | Poltava Oblast | 36000 | Ukraine |
| FG001 | PIP/TAZ FDC | Piperacillin/tazobactam (PIP/TAZ) was 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 were 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 continued to receive 600 mg linezolid every 12 hours for a minimum of 7 days, up to 14 days total. |
| Treated |
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| COMPLETED |
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| NOT COMPLETED |
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|
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| ID | Title | Description |
|---|---|---|
| BG000 | IMI/REL FDC | Imipenem/cilastatin/relebactam (IMI/REL) was 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 were treated empirically with 600 mg open-label linezolid administered IV every 12 hours until methicillin-resistant Staphylococcus aureus (MRSA) was ruled out. Participants with confirmed MRSA infection continued to receive 600 mg linezolid every 12 hours for a minimum of 7 days, up to 14 days total. |
| BG001 | PIP/TAZ FDC | Piperacillin/tazobactam (PIP/TAZ) was 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 were 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 continued to receive 600 mg linezolid every 12 hours for a minimum of 7 days, up to 14 days total. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Randomization strata: Pneumonia type at baseline | Participants were stratified by the following two pneumonia types at baseline: Non-ventilated hospital acquired bacterial pneumonia (HABP) and ventilated HABP/ventilator associated bacterial pneumonia (VABP). | Count of Participants | Participants |
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| Randomization strata: Acute Physiology and Chronic Health Evaluation (APACHE) II score at baseline | APACHE score is a severity-of-disease classification system that is calculated from a participants age and 12 routine physiological measurements. Total scores are computed based on several measurements and range from 0 to 71 with higher scores corresponding to more severe disease and a higher risk of death. Participants were stratified by APACHE II score at baseline <15 vs. >15 | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | The MITT population consisting of all randomized participants who received at least 1 dose of IV study therapy and did not have the presence of positive cocci only on baseline Gram stain were analyzed. | Posted | Number | Percentage of Participants | Up to approximately 28 days |
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| 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. | MITT population consisting of all randomized participants who received at least 1 dose of IV study therapy and did not have the presence of positive cocci only on baseline Gram stain. | Posted | Number | Percentage of Participants | Up to approximately 27 days |
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| 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. | MITT population consisting of all randomized participants who received at least 1 dose of IV study therapy and did not have the presence of positive cocci only on baseline Gram stain. The CE population was a subset of the MITT population who also met important diagnostic criteria for entry into the study, had no significant deviation from the protocol and received the minimum duration of IV study therapy. Only participants with non-missing/non-indeterminate response were assessed at EFU visit. | Posted | Number | Percentage of Participants | Up to approximately 27 days |
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| 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. | MITT population consisting of all randomized participants who received at least 1 dose of IV study therapy and did not have the presence of positive cocci only on baseline Gram stain were analyzed. | Posted | Number | Percentage of Participants | Up to approximately 14 days |
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| 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. | MITT population consisting of all randomized participants who received at least 1 dose of IV study therapy and did not have the presence of positive cocci only on baseline Gram stain. The CE population was a subset of the MITT population who also met important diagnostic criteria for entry into the study, had no significant deviation from the protocol and received the minimum duration of IV study therapy. Only participants with non-missing/non-indeterminate response were assessed at EOT visit. | Posted | Number | Percentage of Participants | Up to approximately 14 days |
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| 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. | The MITT population consisted of all randomized participants who received at least 1 dose of IV study therapy and did not have the presence of positive cocci. The microbiological modified intention-to-treat (mMITT) population was a subset of the MITT population that possessed a baseline bacterial pathogen isolated from a lower respiratory tract (LRT) specimen that was identified as the cause of HABP/VABP and against which IMI/REL has been shown to have antibacterial activity. | Posted | Number | Percentage of Participants | Up to approximately 14 days |
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| 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. | All randomized participants receiving ≥1 dose of IV study therapy without presence of positive cocci (MITT); who met important diagnostic criteria for study with no significant protocol deviation and received minimum duration of IV study therapy (CE); had a baseline bacterial pathogen cause of HABP/VABP against which IMI/REL has antibacterial activity and results from a lower respiratory tract culture obtained at indicated time point (ME); and had non-missing/non-indeterminate response at EFU. | Posted | Number | Percentage of Participants | 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. | All randomized participants receiving ≥1 dose of IV study therapy without presence of positive cocci (MITT); who met important diagnostic criteria for study with no significant protocol deviation and received minimum duration of IV study therapy (CE); had a baseline bacterial pathogen cause of HABP/VABP against which IMI/REL has antibacterial activity and results from a lower respiratory tract culture obtained at indicated time point (ME); and had non-missing/non-indeterminate response at EOT. | Posted | Number | Percentage of Participants | Up to approximately 14 days |
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| 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. | All randomized participants who received at least 1 dose of IV study therapy were assessed. | Posted | Number | Percentage of Participants | Up to approximately 98 days |
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| 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. | All randomized participants who received at least 1 dose of IV study therapy were assessed. | Posted | Number | Percentage of Participants | Up to approximately 14 days |
|
Up to approximately 98 days
All-cause mortality: all randomized participants; Safety: all randomized participants who received at least one dose of study treatment.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | IMI/REL | Imipenem/cilastatin/relebactam (IMI/REL) was 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 were treated empirically with 600 mg open-label linezolid administered IV every 12 hours until methicillin-resistant Staphylococcus aureus (MRSA) was ruled out. Participants with confirmed MRSA infection continued to receive 600 mg linezolid every 12 hours for a minimum of 7 days, up to 14 days total. | 18 | 138 | 29 | 134 | 81 | 134 |
| EG001 | PIP/TAZ | Piperacillin/tazobactam (PIP/TAZ) was 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 were 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 continued to receive 600 mg linezolid every 12 hours for a minimum of 7 days, up to 14 days total. | 11 | 136 | 21 | 136 | 66 | 136 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Cardiac arrest | Cardiac disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Cardio-respiratory arrest | Cardiac disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Ventricular tachyarrhythmia | Cardiac disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Duodenal ulcer haemorrhage | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Gastropleural fistula | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Lower gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Mouth ulceration | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Upper gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Death | General disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Bronchopulmonary aspergillosis | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Endocarditis | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Mediastinitis | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Pneumonia bacterial | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Septic shock | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Tracheobronchitis | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Anastomotic fistula | Injury, poisoning and procedural complications | MedDRA 25.0 | Systematic Assessment |
| |
| Anastomotic leak | Injury, poisoning and procedural complications | MedDRA 25.0 | Systematic Assessment |
| |
| Subdural haematoma | Injury, poisoning and procedural complications | MedDRA 25.0 | Systematic Assessment |
| |
| Traumatic intracranial haemorrhage | Injury, poisoning and procedural complications | MedDRA 25.0 | Systematic Assessment |
| |
| Lung squamous cell carcinoma stage IV | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 25.0 | Systematic Assessment |
| |
| Basal ganglia haemorrhage | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Brain oedema | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Brain stem haemorrhage | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Cerebral haemorrhage | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Cerebral infarction | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Haemorrhage intracranial | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Ruptured cerebral aneurysm | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Subarachnoid haemorrhage | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Chronic kidney disease | Renal and urinary disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Chronic respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Interstitial lung disease | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Dermatitis exfoliative generalised | Skin and subcutaneous tissue disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Circulatory collapse | Vascular disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Shock | Vascular disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Shock haemorrhagic | Vascular disorders | MedDRA 25.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Hepatic function abnormal | Hepatobiliary disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 25.0 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 25.0 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
|
If publication activity is not directed by the Sponsor, the investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission. This allows the Sponsor to protect proprietary information and to provide comments.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme LLC | 1-800-672-6372 | ClinicalTrialsDisclosure@msd.com |
| Jun 27, 2023 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D000069349 | Linezolid |
| ID | Term |
|---|---|
| D000081 | Acetamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D000085 | Acetates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D023303 | Oxazolidinones |
| D010080 | Oxazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Ventilated HABP/VABP |
|
| APACHE II Score ≥15 |
|
| Miettinen & Nurminen |
Adjusted differences and the 95% CIs are based on Miettinen & Nurminen method stratified by randomization stratum. |
| 0.938 |
| Adjusted difference in percentage |
| 5.2 |
| 2-Sided |
| 95 |
| -1.5 |
| 12.4 |
| Superiority |
Piperacillin/tazobactam (PIP/TAZ) was 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 were 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 continued to receive 600 mg linezolid every 12 hours for a minimum of 7 days, up to 14 days total. |
|
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| OG001 | PIP/TAZ FDC | Piperacillin/tazobactam (PIP/TAZ) was 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 were 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 continued to receive 600 mg linezolid every 12 hours for a minimum of 7 days, up to 14 days total. |
|
|
|
Piperacillin/tazobactam (PIP/TAZ) was 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 were 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 continued to receive 600 mg linezolid every 12 hours for a minimum of 7 days, up to 14 days total. |
|
|
|
| OG001 | PIP/TAZ FDC | Piperacillin/tazobactam (PIP/TAZ) was 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 were 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 continued to receive 600 mg linezolid every 12 hours for a minimum of 7 days, up to 14 days total. |
|
|
|
| OG001 | PIP/TAZ FDC | Piperacillin/tazobactam (PIP/TAZ) was 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 were 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 continued to receive 600 mg linezolid every 12 hours for a minimum of 7 days, up to 14 days total. |
|
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| OG001 | PIP/TAZ FDC | Piperacillin/tazobactam (PIP/TAZ) was 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 were 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 continued to receive 600 mg linezolid every 12 hours for a minimum of 7 days, up to 14 days total. |
|
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| OG001 | PIP/TAZ FDC | Piperacillin/tazobactam (PIP/TAZ) was 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 were 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 continued to receive 600 mg linezolid every 12 hours for a minimum of 7 days, up to 14 days total. |
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