Trial Outcomes & Findings for Imipenem/Cilastatin/Relebactam (MK-7655A) Versus Piperacillin/Tazobactam in Participants With Hospital-Acquired or Ventilator-Associated Bacterial Pneumonia (MK-7655A-016) (NCT NCT03583333)

Last Updated: 2025-01-29

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

274 participants

Primary outcome timeframe

Up to approximately 28 days

Results posted on

2025-01-29

Participant Flow

This study was conducted at 54 centers in 8 countries.

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).

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	138	136
Overall Study Treated	134	136
Overall Study COMPLETED	90	106
Overall Study NOT COMPLETED	48	30

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.
Overall Study Participant Conducted Day 28 Visit Prior to the Required Time Window	8	6
Overall Study Withdrawal by Parent/Guardian	16	10
Overall Study Withdrawal by Subject	9	5
Overall Study Physician Decision	3	2
Overall Study Death	12	7

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	IMI/REL FDC n=138 Participants 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.	PIP/TAZ FDC n=136 Participants 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.	Total n=274 Participants Total of all reporting groups
Age, Continuous	55.9 Years STANDARD_DEVIATION 15.1 • n=5 Participants	59.2 Years STANDARD_DEVIATION 14.7 • n=7 Participants	57.5 Years STANDARD_DEVIATION 14.9 • n=5 Participants
Sex: Female, Male Female	37 Participants n=5 Participants	36 Participants n=7 Participants	73 Participants n=5 Participants
Sex: Female, Male Male	101 Participants n=5 Participants	100 Participants n=7 Participants	201 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	8 Participants n=7 Participants	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	134 Participants n=5 Participants	128 Participants n=7 Participants	262 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	110 Participants n=5 Participants	102 Participants n=7 Participants	212 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	27 Participants n=5 Participants	33 Participants n=7 Participants	60 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Randomization strata: Pneumonia type at baseline Non-ventilated HABP	74 Participants n=5 Participants	80 Participants n=7 Participants	154 Participants n=5 Participants
Randomization strata: Pneumonia type at baseline Ventilated HABP/VABP	64 Participants n=5 Participants	56 Participants n=7 Participants	120 Participants n=5 Participants
Randomization strata: Acute Physiology and Chronic Health Evaluation (APACHE) II score at baseline APACHE II Score <15	65 Participants n=5 Participants	61 Participants n=7 Participants	126 Participants n=5 Participants
Randomization strata: Acute Physiology and Chronic Health Evaluation (APACHE) II score at baseline APACHE II Score ≥15	73 Participants n=5 Participants	75 Participants n=7 Participants	148 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to approximately 28 days

Population: 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.

Outcome measures

Outcome measures
Measure	IMI/REL FDC n=134 Participants 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.	PIP/TAZ FDC n=136 Participants 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.
Percentage of Participants With All-cause Mortality Through Day 28 in the Modified Intent to Treat (MITT) Population	11.2 Percentage of Participants	5.9 Percentage of Participants

SECONDARY outcome

Timeframe: Up to approximately 27 days

Population: 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.

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.

Outcome measures

Outcome measures
Measure	IMI/REL FDC n=134 Participants 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.	PIP/TAZ FDC n=136 Participants 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.
Percentage of Participants Achieving a Favorable Clinical Response at Early Follow-up (EFU) Visit in the MITT Population	50.7 Percentage of Participants	47.8 Percentage of Participants

SECONDARY outcome

Timeframe: Up to approximately 27 days

Population: 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.

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.

Outcome measures

Outcome measures
Measure	IMI/REL FDC n=79 Participants 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.	PIP/TAZ FDC n=82 Participants 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.
Percentage of Participants Achieving a Favorable Clinical Response at EFU Visit in the Clinically Evaluable (CE) Population	64.6 Percentage of Participants	62.2 Percentage of Participants

SECONDARY outcome

Timeframe: Up to approximately 14 days

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.

Outcome measures

Outcome measures
Measure	IMI/REL FDC n=134 Participants 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.	PIP/TAZ FDC n=136 Participants 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.
Percentage of Participants Achieving a Favorable Clinical Response at End of Therapy (EOT) Visit in the MITT Population	71.6 Percentage of Participants	68.4 Percentage of Participants

SECONDARY outcome

Timeframe: Up to approximately 14 days

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.

Outcome measures

Outcome measures
Measure	IMI/REL FDC n=106 Participants 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.	PIP/TAZ FDC n=96 Participants 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.
Percentage of Participants Achieving a Favorable Clinical Response at EOT Visit in the Clinically Evaluable (CE) Population	77.4 Percentage of Participants	82.3 Percentage of Participants

SECONDARY outcome

Timeframe: Up to approximately 14 days

Population: 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.

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.

Outcome measures

Outcome measures
Measure	IMI/REL FDC n=80 Participants 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.	PIP/TAZ FDC n=73 Participants 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.
Percentage of Participants Achieving a Favorable Microbiological Response at EOT Visit in Microbiological Modified Intent-To-Treat Population (mMITT) Population	57.5 Percentage of Participants	60.3 Percentage of Participants

SECONDARY outcome

Timeframe: Up to approximately 27 days

Population: 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.

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.

Outcome measures

Outcome measures
Measure	IMI/REL FDC n=45 Participants 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.	PIP/TAZ FDC n=37 Participants 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.
Percentage of Participants Achieving a Favorable Microbiological Response at EFU Visit in Microbiological-evaluable (ME) Population.	80.0 Percentage of Participants	78.4 Percentage of Participants

SECONDARY outcome

Timeframe: Up to approximately 14 days

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.

Outcome measures

Outcome measures
Measure	IMI/REL FDC n=57 Participants 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.	PIP/TAZ FDC n=47 Participants 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.
Percentage of Participants Achieving a Favorable Microbiological Response at EOT Visit in the ME Population	71.9 Percentage of Participants	74.5 Percentage of Participants

SECONDARY outcome

Timeframe: Up to approximately 98 days

Population: All randomized participants who received at least 1 dose of IV study therapy were assessed.

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.

Outcome measures

Outcome measures
Measure	IMI/REL FDC n=134 Participants 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.	PIP/TAZ FDC n=136 Participants 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.
Percentage of Participants Experiencing Adverse Events (AEs)	86.6 Percentage of Participants	84.6 Percentage of Participants

SECONDARY outcome

Timeframe: Up to approximately 14 days

Population: All randomized participants who received at least 1 dose of IV study therapy were assessed.

Outcome measures

Outcome measures
Measure	IMI/REL FDC n=134 Participants 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.	PIP/TAZ FDC n=136 Participants 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.
Percentage of Participants Discontinuing Study Drug Due to AEs	3.7 Percentage of Participants	8.1 Percentage of Participants

Adverse Events

IMI/REL

Serious events: 29 serious events

Other events: 81 other events

Deaths: 18 deaths

PIP/TAZ

Serious events: 21 serious events

Other events: 66 other events

Deaths: 11 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	IMI/REL n=134 participants at risk 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.	PIP/TAZ n=136 participants at risk 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.
Blood and lymphatic system disorders Anaemia	13.4% 18/134 • Number of events 20 • Up to approximately 98 days All-cause mortality: all randomized participants; Safety: all randomized participants who received at least one dose of study treatment.	12.5% 17/136 • Number of events 17 • Up to approximately 98 days All-cause mortality: all randomized participants; Safety: all randomized participants who received at least one dose of study treatment.
Gastrointestinal disorders Constipation	11.2% 15/134 • Number of events 15 • Up to approximately 98 days All-cause mortality: all randomized participants; Safety: all randomized participants who received at least one dose of study treatment.	6.6% 9/136 • Number of events 10 • Up to approximately 98 days All-cause mortality: all randomized participants; Safety: all randomized participants who received at least one dose of study treatment.
Gastrointestinal disorders Diarrhoea	15.7% 21/134 • Number of events 27 • Up to approximately 98 days All-cause mortality: all randomized participants; Safety: all randomized participants who received at least one dose of study treatment.	16.2% 22/136 • Number of events 25 • Up to approximately 98 days All-cause mortality: all randomized participants; Safety: all randomized participants who received at least one dose of study treatment.
Gastrointestinal disorders Vomiting	6.0% 8/134 • Number of events 11 • Up to approximately 98 days All-cause mortality: all randomized participants; Safety: all randomized participants who received at least one dose of study treatment.	4.4% 6/136 • Number of events 6 • Up to approximately 98 days All-cause mortality: all randomized participants; Safety: all randomized participants who received at least one dose of study treatment.
Hepatobiliary disorders Hepatic function abnormal	12.7% 17/134 • Number of events 18 • Up to approximately 98 days All-cause mortality: all randomized participants; Safety: all randomized participants who received at least one dose of study treatment.	9.6% 13/136 • Number of events 13 • Up to approximately 98 days All-cause mortality: all randomized participants; Safety: all randomized participants who received at least one dose of study treatment.
Infections and infestations Urinary tract infection	6.0% 8/134 • Number of events 8 • Up to approximately 98 days All-cause mortality: all randomized participants; Safety: all randomized participants who received at least one dose of study treatment.	2.9% 4/136 • Number of events 4 • Up to approximately 98 days All-cause mortality: all randomized participants; Safety: all randomized participants who received at least one dose of study treatment.
Investigations Alanine aminotransferase increased	9.0% 12/134 • Number of events 12 • Up to approximately 98 days All-cause mortality: all randomized participants; Safety: all randomized participants who received at least one dose of study treatment.	9.6% 13/136 • Number of events 13 • Up to approximately 98 days All-cause mortality: all randomized participants; Safety: all randomized participants who received at least one dose of study treatment.
Investigations Aspartate aminotransferase increased	6.0% 8/134 • Number of events 8 • Up to approximately 98 days All-cause mortality: all randomized participants; Safety: all randomized participants who received at least one dose of study treatment.	5.1% 7/136 • Number of events 7 • Up to approximately 98 days All-cause mortality: all randomized participants; Safety: all randomized participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Hypokalaemia	9.7% 13/134 • Number of events 14 • Up to approximately 98 days All-cause mortality: all randomized participants; Safety: all randomized participants who received at least one dose of study treatment.	12.5% 17/136 • Number of events 19 • Up to approximately 98 days All-cause mortality: all randomized participants; Safety: all randomized participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Hyponatraemia	12.7% 17/134 • Number of events 18 • Up to approximately 98 days All-cause mortality: all randomized participants; Safety: all randomized participants who received at least one dose of study treatment.	6.6% 9/136 • Number of events 9 • Up to approximately 98 days All-cause mortality: all randomized participants; Safety: all randomized participants who received at least one dose of study treatment.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme LLC

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER