Trial Outcomes & Findings for PHASE II SINGLE-CENTER, RANDOMIZED, OPEN-LABEL, PROSPECTIVE, STUDY TO DETERMINE THE IMPACT OF SERIAL PROCALCITONIN (NCT NCT04983901)

Last Updated: 2024-11-04

Results Overview

The primary efficacy outcome is favorable clinical response of the patients in the MITT (Modified Intent-To-Treat) Analysis Set at end of inpatient intravenous therapy (EOIV). The clinical outcome has three categories: Favorable clinical response, Clinical failure, and Indeterminate.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

100 participants

Primary outcome timeframe

Within 72 hours after administration of the last dose of inpatient IV study drug.

Results posted on

2024-11-04

Participant Flow

Between September 14, 2021 and October 06, 2023, patients presenting to the emergency medicine department were screened through an EPIC generated list identifying patients with fever and neutropenia that meet the inclusion criteria.

Participant milestones

Participant milestones
Measure	Imipenem-Relebactam Arm Patients receive imipenem/cilastatin/relebactam IV over 30-60 minutes once every 6 hours (q6h) for 2 days for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or orally (PO) q12h. Daptomycion could be given if no pneumonia. Participants may continue on the study drug for up to 14 days. Participants may receive other addtional therapy.	Standard of Care (SOC) Arm Patients receive cefepime IV q8h for a minimum of 6 doses, or meropenem IV q8h for a minimum of 6 doses, or piperacillin/tazobactam IV q6h for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or orally (PO) q12h. Daptomycion could be given if no pneumonia. Patients may receive other additional therapy.
Overall Study STARTED	50	50
Overall Study COMPLETED	44	44
Overall Study NOT COMPLETED	6	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Imipenem-Relebactam Arm Patients receive imipenem/cilastatin/relebactam IV over 30-60 minutes once every 6 hours (q6h) for 2 days for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or orally (PO) q12h. Daptomycion could be given if no pneumonia. Participants may continue on the study drug for up to 14 days. Participants may receive other addtional therapy.	Standard of Care (SOC) Arm Patients receive cefepime IV q8h for a minimum of 6 doses, or meropenem IV q8h for a minimum of 6 doses, or piperacillin/tazobactam IV q6h for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or orally (PO) q12h. Daptomycion could be given if no pneumonia. Patients may receive other additional therapy.
Overall Study Death	1	4
Overall Study Lost to Follow-up	3	0
Overall Study Protocol Violation	1	0
Overall Study Withdrawal by Subject	1	2

Baseline Characteristics

History of BMT within one year

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Imipenem-Relebactam Arm n=49 Participants Patients receive imipenem/cilastatin/relebactam IV over 30-60 minutes once every 6 hours (q6h) for 2 days for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or orally (PO) q12h. Daptomycion could be given if no pneumonia. Participants may continue on the study drug for up to 14 days. Participants may receive other addtional therapy.	Standard of Care (SOC) Arm n=50 Participants Patients receive cefepime IV q8h for a minimum of 6 doses, or meropenem IV q8h for a minimum of 6 doses, or piperacillin/tazobactam IV q6h for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or orally (PO) q12h. Daptomycion could be given if no pneumonia. Patients may receive other additional therapy.	Total n=99 Participants Total of all reporting groups
Sepsis status No sepsis	35 Participants n=93 Participants	35 Participants n=4 Participants	70 Participants n=27 Participants
Sepsis status Sepsis	14 Participants n=93 Participants	14 Participants n=4 Participants	28 Participants n=27 Participants
Sepsis status Severe sepsis	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Neurologic impairment Neurologic impairment	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Neurologic impairment Confusion	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Age, Continuous	55 years n=93 Participants	63 years n=4 Participants	61 years n=27 Participants
Sex: Female, Male Female	23 Participants n=93 Participants	23 Participants n=4 Participants	46 Participants n=27 Participants
Sex: Female, Male Male	26 Participants n=93 Participants	27 Participants n=4 Participants	53 Participants n=27 Participants
Race/Ethnicity, Customized Asian	3 Participants n=93 Participants	1 Participants n=4 Participants	4 Participants n=27 Participants
Race/Ethnicity, Customized Black or African American	4 Participants n=93 Participants	5 Participants n=4 Participants	9 Participants n=27 Participants
Race/Ethnicity, Customized Hispanic or Latino	8 Participants n=93 Participants	4 Participants n=4 Participants	12 Participants n=27 Participants
Race/Ethnicity, Customized Middle East	1 Participants n=93 Participants	1 Participants n=4 Participants	2 Participants n=27 Participants
Race/Ethnicity, Customized White	33 Participants n=93 Participants	38 Participants n=4 Participants	71 Participants n=27 Participants
Race/Ethnicity, Customized Others	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Region of Enrollment United States	49 participants n=93 Participants	50 participants n=4 Participants	99 participants n=27 Participants
Type of Cancer Hematological malignancy	33 Participants n=93 Participants	31 Participants n=4 Participants	64 Participants n=27 Participants
Type of Cancer Solid tumor	16 Participants n=93 Participants	19 Participants n=4 Participants	35 Participants n=27 Participants
History of BMT within one year History of BMT within one year	3 Participants n=93 Participants • History of BMT within one year	6 Participants n=4 Participants • History of BMT within one year	9 Participants n=27 Participants • History of BMT within one year
History of BMT within one year Autologous	0 Participants n=93 Participants • History of BMT within one year	3 Participants n=4 Participants • History of BMT within one year	3 Participants n=27 Participants • History of BMT within one year
History of BMT within one year Allogeniec	3 Participants n=93 Participants • History of BMT within one year	3 Participants n=4 Participants • History of BMT within one year	6 Participants n=27 Participants • History of BMT within one year
Type of allogeneic transplant Matched unrelated donor	2 Participants n=93 Participants	2 Participants n=4 Participants	4 Participants n=27 Participants
Type of allogeneic transplant HLA matched related	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Type of allogeneic transplant Others	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Type of allogeneic transplant GVHD	2 Participants n=93 Participants	2 Participants n=4 Participants	4 Participants n=27 Participants
Temperature at initial presentation (oC) < 36	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Temperature at initial presentation (oC) 36-38	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Temperature at initial presentation (oC) > 38	49 Participants n=93 Participants	50 Participants n=4 Participants	99 Participants n=27 Participants
Clinical source presentation	26 Participants n=93 Participants	25 Participants n=4 Participants	51 Participants n=27 Participants
Site of clinical presentation Head and neck	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Site of clinical presentation Lung (pneumonia)	18 Participants n=93 Participants	19 Participants n=4 Participants	37 Participants n=27 Participants
Site of clinical presentation Abdomen	7 Participants n=93 Participants	4 Participants n=4 Participants	11 Participants n=27 Participants
Site of clinical presentation Genitourinary	1 Participants n=93 Participants	2 Participants n=4 Participants	3 Participants n=27 Participants
Site of clinical presentation Skin and soft tissue	1 Participants n=93 Participants	1 Participants n=4 Participants	2 Participants n=27 Participants
Microbiological documentation (positivity)	13 Participants n=93 Participants	17 Participants n=4 Participants	30 Participants n=27 Participants
Site of organism Genitourinary	0 Participants n=93 Participants	2 Participants n=4 Participants	2 Participants n=27 Participants
Site of organism Blood	13 Participants n=93 Participants	15 Participants n=4 Participants	28 Participants n=27 Participants
Organisms identified Organisms identified	13 Participants n=93 Participants	17 Participants n=4 Participants	30 Participants n=27 Participants
Organisms identified Gram negative	7 Participants n=93 Participants	8 Participants n=4 Participants	15 Participants n=27 Participants
Organisms identified Gram positive	6 Participants n=93 Participants	5 Participants n=4 Participants	11 Participants n=27 Participants
Organisms identified Both Gram Positive and Gram Negative	0 Participants n=93 Participants	4 Participants n=4 Participants	4 Participants n=27 Participants
Organisms recovered in positive cultures Organisms recovered in positive cultures	13 Participants n=93 Participants	17 Participants n=4 Participants	30 Participants n=27 Participants
Organisms recovered in positive cultures Enterobacter cloacae	2 Participants n=93 Participants	1 Participants n=4 Participants	3 Participants n=27 Participants
Organisms recovered in positive cultures Escherichia coli	3 Participants n=93 Participants	3 Participants n=4 Participants	6 Participants n=27 Participants
Organisms recovered in positive cultures Klebsiella pneumoniae	0 Participants n=93 Participants	2 Participants n=4 Participants	2 Participants n=27 Participants
Organisms recovered in positive cultures Pseudomonas aeruginosa	1 Participants n=93 Participants	2 Participants n=4 Participants	3 Participants n=27 Participants
Organisms recovered in positive cultures Rhizobium radiobacter	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Organisms recovered in positive cultures Klebsiella pneumoniae & Enterococcus faecalis	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Organisms recovered in positive cultures Haemophilus parainfluenzae & Streptococcus mitis/oralis Group	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Organisms recovered in positive cultures Pseudomonas aeruginosa, Streptococcus mitis/oralis Group & Enterococcus faecalis	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Organisms recovered in positive cultures Roseomonas mucosa, Micrococcus luteus & Dermacoccus nishinomiyaensis	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Organisms recovered in positive cultures Enterococcus faecium	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Organisms recovered in positive cultures Staphylococcus epidermidis	1 Participants n=93 Participants	2 Participants n=4 Participants	3 Participants n=27 Participants
Organisms recovered in positive cultures Streptococcus mitis/oralis group	4 Participants n=93 Participants	2 Participants n=4 Participants	6 Participants n=27 Participants
Organisms recovered in positive cultures Enterococcus faecalis & Rothia mucilaginosa	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Bacteremia	13 Participants n=93 Participants	15 Participants n=4 Participants	28 Participants n=27 Participants
CVC being the source of BSI isolation	12 Participants n=93 Participants	11 Participants n=4 Participants	23 Participants n=27 Participants
SOC Antibiotics Cefepime	0 Participants n=93 Participants	43 Participants n=4 Participants	43 Participants n=27 Participants
SOC Antibiotics Meropenem	0 Participants n=93 Participants	2 Participants n=4 Participants	2 Participants n=27 Participants
SOC Antibiotics Piperacillin/tazobactam	0 Participants n=93 Participants	5 Participants n=4 Participants	5 Participants n=27 Participants
Antibiotics for gram positive coverage Vancomycin	20 Participants n=93 Participants	20 Participants n=4 Participants	40 Participants n=27 Participants
Antibiotics for gram positive coverage Linezolid	18 Participants n=93 Participants	27 Participants n=4 Participants	45 Participants n=27 Participants
Antibiotics for gram positive coverage Daptomycin	3 Participants n=93 Participants	1 Participants n=4 Participants	4 Participants n=27 Participants
Antibiotics for gram positive coverage Linezolid & daptomycin	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Antibiotics for gram positive coverage None	7 Participants n=93 Participants	2 Participants n=4 Participants	9 Participants n=27 Participants
Gram positive coverage with any of the above antibiotics	42 Participants n=93 Participants	48 Participants n=4 Participants	90 Participants n=27 Participants
ICU admission	3 Participants n=93 Participants	2 Participants n=4 Participants	5 Participants n=27 Participants
Mechanical ventilation	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants

PRIMARY outcome

Timeframe: Within 72 hours after administration of the last dose of inpatient IV study drug.

Population: Patients in MITT (Modified Intent-To-Treat) Analysis Set The MITT Analysis Set will be a subset of the ITT Analysis Set and will include all randomized patients who received any amount of inpatient IV study drug and meet minimal disease criteria (Inclusion Criterion 3). Patients will be analyzed according to randomized treatment group, regardless of treatment received.

Outcome measures

Outcome measures
Measure	Imipenem-Relebactam Arm n=49 Participants Patients receive imipenem/cilastatin/relebactam IV over 30-60 minutes once every 6 hours (q6h) for 2 days for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or Patients may continue on the study drug for up to 14 days. Patients may receive other additional therapy..	Standard of Care (SOC) Arm n=50 Participants Patients receive cefepime IV q8h for a minimum of 6 doses, or meropenem IV q8h for a minimum of 6 doses, or piperacillin/tazobactam IV q6h for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or orally (PO) q12h. Daptomycion could be given if no pneumonia. Patients may receive other additional therapy.
Clinical Outcome in the MITT Analysis Set at EOIV. Favorable clinical resposne	44 Participants	37 Participants
Clinical Outcome in the MITT Analysis Set at EOIV. Clinical failure	5 Participants	12 Participants
Clinical Outcome in the MITT Analysis Set at EOIV. Indeterminate	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Within 72 hours after administration of the last dose of inpatient IV study drug.

Population: Patients in mMITT (Microbiological Modified Intent-To-Treat) Analysis Set The mMITT Analysis Set will be a subset of the MITT Analysis Set and will include those patients for whom at least 1 qualifying bacterial pathogen was isolated from an appropriate microbiological specimen at baseline, irrespective of susceptibility to study therapies

The secondary efficacy outcome is favorable clinical response of the patients in the mMITT (Microbiological Modified Intent-To-Treat) Analysis Set at end of inpatient intravenous therapy (EOIV). The clinical outcome has three categories: Favorable clinical response, Clinical failure, and Indeterminate.

Outcome measures

Outcome measures
Measure	Imipenem-Relebactam Arm n=7 Participants Patients receive imipenem/cilastatin/relebactam IV over 30-60 minutes once every 6 hours (q6h) for 2 days for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or Patients may continue on the study drug for up to 14 days. Patients may receive other additional therapy..	Standard of Care (SOC) Arm n=12 Participants Patients receive cefepime IV q8h for a minimum of 6 doses, or meropenem IV q8h for a minimum of 6 doses, or piperacillin/tazobactam IV q6h for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or orally (PO) q12h. Daptomycion could be given if no pneumonia. Patients may receive other additional therapy.
Clinical Outcome in the mMITT Analysis Set at EOIV. Favorable clinical resposne	6 Participants	8 Participants
Clinical Outcome in the mMITT Analysis Set at EOIV. Clinical failure	1 Participants	3 Participants
Clinical Outcome in the mMITT Analysis Set at EOIV. Indeterminate	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Within 72 hours after administration of the last dose of inpatient IV study drug.

Population: Patients in CE (Clinically Evaluable) Analysis Set - A subset of the MITT Analysis Set including patients with the following conditions: Received \>=48 hrs of IV study drug to be considered an evaluable clinical failure, unless deemed a clinical failure based on a treatment-limiting AE Received \>=48 hrs of IV gram negative coverage to be considered an evaluable clinical cure Had clinical outcome assessment at TOC (other than indeterminate) or assessed as clinical failure at EOIV or TOC

The secondary efficacy outcome is favorable clinical response of the patients in the CE (Clinically Evaluable) Analysis Set at end of inpatient intravenous therapy (EOIV). The clinical outcome has three categories: Favorable clinical response, Clinical failure, and Indeterminate.

Outcome measures

Outcome measures
Measure	Imipenem-Relebactam Arm n=42 Participants Patients receive imipenem/cilastatin/relebactam IV over 30-60 minutes once every 6 hours (q6h) for 2 days for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or Patients may continue on the study drug for up to 14 days. Patients may receive other additional therapy..	Standard of Care (SOC) Arm n=35 Participants Patients receive cefepime IV q8h for a minimum of 6 doses, or meropenem IV q8h for a minimum of 6 doses, or piperacillin/tazobactam IV q6h for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or orally (PO) q12h. Daptomycion could be given if no pneumonia. Patients may receive other additional therapy.
Clinical Outcome in the CE Analysis Set at EOIV. Favorable clinical resposne	37 Participants	26 Participants
Clinical Outcome in the CE Analysis Set at EOIV. Clinical failure	5 Participants	9 Participants

SECONDARY outcome

Timeframe: 21 to 28 days after the start of inpatient IV study drug.

Population: Pateints in MITT (Modified Intent-To-Treat) Analysis Set The MITT Analysis Set will be a subset of the ITT Analysis Set and will include all randomized patients who received any amount of inpatient IV study drug and meet minimal disease criteria (Inclusion Criterion 3). Patients will be analyzed according to randomized treatment group, regardless of treatment received.

The secondary efficacy outcome is favorable clinical response of the patients in the MITT (Modified Intent-To-Treat) Analysis Set at test-of-cure (TOC). The clinical outcome has three categories: Clinical cure, Clinical failure, and Indeterminate.

Outcome measures

Outcome measures
Measure	Imipenem-Relebactam Arm n=49 Participants Patients receive imipenem/cilastatin/relebactam IV over 30-60 minutes once every 6 hours (q6h) for 2 days for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or Patients may continue on the study drug for up to 14 days. Patients may receive other additional therapy..	Standard of Care (SOC) Arm n=50 Participants Patients receive cefepime IV q8h for a minimum of 6 doses, or meropenem IV q8h for a minimum of 6 doses, or piperacillin/tazobactam IV q6h for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or orally (PO) q12h. Daptomycion could be given if no pneumonia. Patients may receive other additional therapy.
Clinical Outcome in the MITT Analysis Set at TOC. Clinical cure	35 Participants	32 Participants
Clinical Outcome in the MITT Analysis Set at TOC. Clinical failure	8 Participants	13 Participants
Clinical Outcome in the MITT Analysis Set at TOC. Indeterminate	6 Participants	5 Participants

SECONDARY outcome

Timeframe: 35 to 42 days after the start of inpatient IV study drug.

The secondary efficacy outcome is favorable clinical response of the patients in the MITT (Modified Intent-To-Treat) Analysis Set at late follow-up (LFU). The clinical outcome has three categories: Clinical cure, Clinical failure, and Indeterminate.

Outcome measures

Outcome measures
Measure	Imipenem-Relebactam Arm n=49 Participants Patients receive imipenem/cilastatin/relebactam IV over 30-60 minutes once every 6 hours (q6h) for 2 days for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or Patients may continue on the study drug for up to 14 days. Patients may receive other additional therapy..	Standard of Care (SOC) Arm n=50 Participants Patients receive cefepime IV q8h for a minimum of 6 doses, or meropenem IV q8h for a minimum of 6 doses, or piperacillin/tazobactam IV q6h for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or orally (PO) q12h. Daptomycion could be given if no pneumonia. Patients may receive other additional therapy.
Clinical Outcome in the MITT Analysis Set at LFU. Clinical cure	33 Participants	30 Participants
Clinical Outcome in the MITT Analysis Set at LFU. Clinical failure	8 Participants	13 Participants
Clinical Outcome in the MITT Analysis Set at LFU. Indeterminate	8 Participants	7 Participants

SECONDARY outcome

Timeframe: 21 to 28 days after the start of inpatient IV study drug.

The secondary efficacy outcome is favorable clinical response of the patients in the mMITT (Microbiological Modified Intent-To-Treat) Analysis Set at test-of-cure (TOC). The clinical outcome has three categories: Clinical cure, Clinical failure, and Indeterminate.

Outcome measures

Outcome measures
Measure	Imipenem-Relebactam Arm n=7 Participants Patients receive imipenem/cilastatin/relebactam IV over 30-60 minutes once every 6 hours (q6h) for 2 days for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or Patients may continue on the study drug for up to 14 days. Patients may receive other additional therapy..	Standard of Care (SOC) Arm n=12 Participants Patients receive cefepime IV q8h for a minimum of 6 doses, or meropenem IV q8h for a minimum of 6 doses, or piperacillin/tazobactam IV q6h for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or orally (PO) q12h. Daptomycion could be given if no pneumonia. Patients may receive other additional therapy.
Clinical Outcome in the mMITT Analysis Set at TOC. Indeterminate	2 Participants	2 Participants
Clinical Outcome in the mMITT Analysis Set at TOC. Clinical cure	3 Participants	6 Participants
Clinical Outcome in the mMITT Analysis Set at TOC. Clinical failure	2 Participants	4 Participants

SECONDARY outcome

Timeframe: Pateints in mMITT (Microbiological Modified Intent-To-Treat) Analysis Set

The secondary efficacy outcome is favorable clinical response of the patients in the mMITT (Microbiological Modified Intent-To-Treat) Analysis Set at late follow-up (LFU). The clinical outcome has three categories: Clinical cure, Clinical failure, and Indeterminate.

Outcome measures

Outcome measures
Measure	Imipenem-Relebactam Arm n=7 Participants Patients receive imipenem/cilastatin/relebactam IV over 30-60 minutes once every 6 hours (q6h) for 2 days for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or Patients may continue on the study drug for up to 14 days. Patients may receive other additional therapy..	Standard of Care (SOC) Arm n=12 Participants Patients receive cefepime IV q8h for a minimum of 6 doses, or meropenem IV q8h for a minimum of 6 doses, or piperacillin/tazobactam IV q6h for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or orally (PO) q12h. Daptomycion could be given if no pneumonia. Patients may receive other additional therapy.
Clinical Outcome in the mMITT Analysis Set at LFU. Clinical cure	3 Participants	6 Participants
Clinical Outcome in the mMITT Analysis Set at LFU. Clinical failure	2 Participants	4 Participants
Clinical Outcome in the mMITT Analysis Set at LFU. Indeterminate	2 Participants	2 Participants

SECONDARY outcome

Timeframe: 21 to 28 days after the start of inpatient IV study drug.

The secondary efficacy outcome is favorable clinical response of the patients in the CE (Clinically Evaluable) Analysis Set at test-of-cure (TOC). The clinical outcome has three categories: Clinical cure, Clinical failure, and Indeterminate.

Outcome measures

Outcome measures
Measure	Imipenem-Relebactam Arm n=42 Participants Patients receive imipenem/cilastatin/relebactam IV over 30-60 minutes once every 6 hours (q6h) for 2 days for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or Patients may continue on the study drug for up to 14 days. Patients may receive other additional therapy..	Standard of Care (SOC) Arm n=35 Participants Patients receive cefepime IV q8h for a minimum of 6 doses, or meropenem IV q8h for a minimum of 6 doses, or piperacillin/tazobactam IV q6h for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or orally (PO) q12h. Daptomycion could be given if no pneumonia. Patients may receive other additional therapy.
Clinical Outcome in the CE Analysis Set at TOC. Clinical cure	34 Participants	25 Participants
Clinical Outcome in the CE Analysis Set at TOC. Clinical failure	8 Participants	10 Participants

SECONDARY outcome

Timeframe: 35 to 42 days after the start of inpatient IV study drug.

The secondary efficacy outcome is favorable clinical response of the patients in the CE (Clinically Evaluable) Analysis Set at late follow-up (LFU). The clinical outcome has three categories: Clinical cure, Clinical failure, and Indeterminate.

Outcome measures

Outcome measures
Measure	Imipenem-Relebactam Arm n=42 Participants Patients receive imipenem/cilastatin/relebactam IV over 30-60 minutes once every 6 hours (q6h) for 2 days for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or Patients may continue on the study drug for up to 14 days. Patients may receive other additional therapy..	Standard of Care (SOC) Arm n=35 Participants Patients receive cefepime IV q8h for a minimum of 6 doses, or meropenem IV q8h for a minimum of 6 doses, or piperacillin/tazobactam IV q6h for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or orally (PO) q12h. Daptomycion could be given if no pneumonia. Patients may receive other additional therapy.
Clinical Outcome in the CE Analysis Set at LFU. Clinical cure	32 Participants	23 Participants
Clinical Outcome in the CE Analysis Set at LFU. Clinical failure	8 Participants	10 Participants
Clinical Outcome in the CE Analysis Set at LFU. Indeterminate	2 Participants	2 Participants

SECONDARY outcome

Timeframe: Within 72 hours after administration of the last dose of inpatient IV study drug.

Population: Patients in ME (Microbiologically Evaluable) Analysis Set The ME Analysis Set will include patients who meet the criteria for both the CE and mMITT analysis sets.

The secondary efficacy outcome is favorable clinical response of the patients in the ME (Microbiologically Evaluable) Analysis Set at end of inpatient intravenous therapy (EOIV). The clinical outcome has three categories: Favorable clinical response, Clinical failure, and Indeterminate.

Outcome measures

Outcome measures
Measure	Imipenem-Relebactam Arm n=5 Participants Patients receive imipenem/cilastatin/relebactam IV over 30-60 minutes once every 6 hours (q6h) for 2 days for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or Patients may continue on the study drug for up to 14 days. Patients may receive other additional therapy..	Standard of Care (SOC) Arm n=7 Participants Patients receive cefepime IV q8h for a minimum of 6 doses, or meropenem IV q8h for a minimum of 6 doses, or piperacillin/tazobactam IV q6h for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or orally (PO) q12h. Daptomycion could be given if no pneumonia. Patients may receive other additional therapy.
Clinical Outcome in the ME Analysis Set at EOIV. Clinical failure	1 Participants	1 Participants
Clinical Outcome in the ME Analysis Set at EOIV. Favorable clinical resposne	4 Participants	6 Participants

SECONDARY outcome

Timeframe: 21 to 28 days after the start of inpatient IV study drug.

Population: Patients in ME (Microbiologically Evaluable) Analysis Set The ME Analysis Set will include patients who meet the criteria for both the CE and mMITT analysis sets.

The secondary efficacy outcome is favorable clinical response of the patients in the ME (Microbiologically Evaluable) Analysis Set at test-of-cure (TOC). The clinical outcome has three categories: Clinical cure, Clinical failure, and Indeterminate.

Outcome measures

Outcome measures
Measure	Imipenem-Relebactam Arm n=5 Participants Patients receive imipenem/cilastatin/relebactam IV over 30-60 minutes once every 6 hours (q6h) for 2 days for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or Patients may continue on the study drug for up to 14 days. Patients may receive other additional therapy..	Standard of Care (SOC) Arm n=7 Participants Patients receive cefepime IV q8h for a minimum of 6 doses, or meropenem IV q8h for a minimum of 6 doses, or piperacillin/tazobactam IV q6h for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or orally (PO) q12h. Daptomycion could be given if no pneumonia. Patients may receive other additional therapy.
Clinical Outcome in the ME Analysis Set at TOC. Clinical cure	3 Participants	5 Participants
Clinical Outcome in the ME Analysis Set at TOC. Clinical failure	2 Participants	2 Participants

SECONDARY outcome

Timeframe: 35 to 42 days after the start of inpatient IV study drug.

Population: Patients in ME (Microbiologically Evaluable) Analysis Set The ME Analysis Set will include patients who meet the criteria for both the CE and mMITT analysis sets.

The secondary efficacy outcome is favorable clinical response of the patients in the ME (Microbiologically Evaluable) Analysis Set at late follow-up (LFU). The clinical outcome has three categories: Clinical cure, Clinical failure, and Indeterminate.

Outcome measures

Outcome measures
Measure	Imipenem-Relebactam Arm n=5 Participants Patients receive imipenem/cilastatin/relebactam IV over 30-60 minutes once every 6 hours (q6h) for 2 days for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or Patients may continue on the study drug for up to 14 days. Patients may receive other additional therapy..	Standard of Care (SOC) Arm n=7 Participants Patients receive cefepime IV q8h for a minimum of 6 doses, or meropenem IV q8h for a minimum of 6 doses, or piperacillin/tazobactam IV q6h for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or orally (PO) q12h. Daptomycion could be given if no pneumonia. Patients may receive other additional therapy.
Clinical Outcome in the ME Analysis Set at LFU. Clinical cure	3 Participants	5 Participants
Clinical Outcome in the ME Analysis Set at LFU. Clinical failure	2 Participants	2 Participants

SECONDARY outcome

Timeframe: Within 72 hours after administration of the last dose of inpatient IV study drug.

The secondary efficacy outcome is favorable microbiological response of the patients in the mMITT (Microbiological Modified Intent-To-Treat) Analysis Set at end of inpatient intravenous therapy (EOIV). The microbiological response outcome has five categories: Persistence, eradication, presumed eradication, presumed persistence, and Indeterminate.

Outcome measures

Outcome measures
Measure	Imipenem-Relebactam Arm n=7 Participants Patients receive imipenem/cilastatin/relebactam IV over 30-60 minutes once every 6 hours (q6h) for 2 days for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or Patients may continue on the study drug for up to 14 days. Patients may receive other additional therapy..	Standard of Care (SOC) Arm n=12 Participants Patients receive cefepime IV q8h for a minimum of 6 doses, or meropenem IV q8h for a minimum of 6 doses, or piperacillin/tazobactam IV q6h for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or orally (PO) q12h. Daptomycion could be given if no pneumonia. Patients may receive other additional therapy.
Microbiological Outcome in the mMITT Analysis Set at EOIV. Eradication	7 Participants	9 Participants
Microbiological Outcome in the mMITT Analysis Set at EOIV. Presumed eradication	0 Participants	2 Participants
Microbiological Outcome in the mMITT Analysis Set at EOIV. Indeterminate	0 Participants	1 Participants

SECONDARY outcome

Timeframe: 21 to 28 days after the start of inpatient IV study drug.

The secondary efficacy outcome is favorable microbiological response of the patients in the mMITT (Microbiological Modified Intent-To-Treat) Analysis Set at test-of-cure (TOC). The microbiological response outcome has five categories: Persistence, eradication, presumed eradication, presumed persistence, and Indeterminate.

Outcome measures

Outcome measures
Measure	Imipenem-Relebactam Arm n=7 Participants Patients receive imipenem/cilastatin/relebactam IV over 30-60 minutes once every 6 hours (q6h) for 2 days for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or Patients may continue on the study drug for up to 14 days. Patients may receive other additional therapy..	Standard of Care (SOC) Arm n=12 Participants Patients receive cefepime IV q8h for a minimum of 6 doses, or meropenem IV q8h for a minimum of 6 doses, or piperacillin/tazobactam IV q6h for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or orally (PO) q12h. Daptomycion could be given if no pneumonia. Patients may receive other additional therapy.
Microbiological Outcome in the mMITT Analysis Set at TOC. Presumed eradication	0 Participants	1 Participants
Microbiological Outcome in the mMITT Analysis Set at TOC. Indeterminate	2 Participants	1 Participants
Microbiological Outcome in the mMITT Analysis Set at TOC. Eradication	5 Participants	10 Participants

SECONDARY outcome

Timeframe: 35 to 42 days after the start of inpatient IV study drug.

The secondary efficacy outcome is favorable microbiological response of the patients in the mMITT (Microbiological Modified Intent-To-Treat) Analysis Set at late follow-up (LFU). The microbiological response outcome has five categories: Persistence, eradication, presumed eradication, presumed persistence, and Indeterminate.

Outcome measures

Outcome measures
Measure	Imipenem-Relebactam Arm n=7 Participants Patients receive imipenem/cilastatin/relebactam IV over 30-60 minutes once every 6 hours (q6h) for 2 days for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or Patients may continue on the study drug for up to 14 days. Patients may receive other additional therapy..	Standard of Care (SOC) Arm n=12 Participants Patients receive cefepime IV q8h for a minimum of 6 doses, or meropenem IV q8h for a minimum of 6 doses, or piperacillin/tazobactam IV q6h for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or orally (PO) q12h. Daptomycion could be given if no pneumonia. Patients may receive other additional therapy.
Microbiological Outcome in the mMITT Analysis Set at LFU. Eradication	5 Participants	10 Participants
Microbiological Outcome in the mMITT Analysis Set at LFU. Presumed eradication	0 Participants	1 Participants
Microbiological Outcome in the mMITT Analysis Set at LFU. Indeterminate	2 Participants	1 Participants

SECONDARY outcome

Timeframe: Within 72 hours after administration of the last dose of inpatient IV study drug.

Population: Patients in ME (Microbiologically Evaluable) Analysis Set The ME Analysis Set will include patients who meet the criteria for both the CE and mMITT analysis sets.

The secondary efficacy outcome is favorable microbiological response of the patients in the ME (Microbiologically Evaluable) Analysis Set at end of inpatient intravenous therapy (EOIV). The microbiological response outcome has five categories: Persistence, eradication, presumed eradication, presumed persistence, and Indeterminate.

Outcome measures

Outcome measures
Measure	Imipenem-Relebactam Arm n=5 Participants Patients receive imipenem/cilastatin/relebactam IV over 30-60 minutes once every 6 hours (q6h) for 2 days for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or Patients may continue on the study drug for up to 14 days. Patients may receive other additional therapy..	Standard of Care (SOC) Arm n=7 Participants Patients receive cefepime IV q8h for a minimum of 6 doses, or meropenem IV q8h for a minimum of 6 doses, or piperacillin/tazobactam IV q6h for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or orally (PO) q12h. Daptomycion could be given if no pneumonia. Patients may receive other additional therapy.
Microbiological Outcome in the ME Analysis Set at EOIV. Eradication	5 Participants	5 Participants
Microbiological Outcome in the ME Analysis Set at EOIV. Presumed eradication	0 Participants	2 Participants

SECONDARY outcome

Timeframe: 21 to 28 days after the start of inpatient IV study drug.

Population: Patients in ME (Microbiologically Evaluable) Analysis Set The ME Analysis Set will include patients who meet the criteria for both the CE and mMITT analysis sets.

The secondary efficacy outcome is favorable microbiological response of the patients in the ME (Microbiologically Evaluable) Analysis Set at test-of-cure (TOC). The microbiological response outcome has five categories: Persistence, eradication, presumed eradication, presumed persistence, and Indeterminate.

Outcome measures

Outcome measures
Measure	Imipenem-Relebactam Arm n=5 Participants Patients receive imipenem/cilastatin/relebactam IV over 30-60 minutes once every 6 hours (q6h) for 2 days for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or Patients may continue on the study drug for up to 14 days. Patients may receive other additional therapy..	Standard of Care (SOC) Arm n=7 Participants Patients receive cefepime IV q8h for a minimum of 6 doses, or meropenem IV q8h for a minimum of 6 doses, or piperacillin/tazobactam IV q6h for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or orally (PO) q12h. Daptomycion could be given if no pneumonia. Patients may receive other additional therapy.
Microbiological Outcome in the ME Analysis Set at TOC. Eradication	5 Participants	6 Participants
Microbiological Outcome in the ME Analysis Set at TOC. Presumed eradication	0 Participants	1 Participants

SECONDARY outcome

Timeframe: 35 to 42 days after the start of inpatient IV study drug.

Population: Patients in ME (Microbiologically Evaluable) Analysis Set The ME Analysis Set will include patients who meet the criteria for both the CE and mMITT analysis sets.

The secondary efficacy outcome is favorable microbiological response of the participants in the ME (Microbiologically Evaluable) Analysis Set at late follow-up (LFU). The microbiological response outcome has five categories: Persistence, eradication, presumed eradication, presumed persistence, and Indeterminate.

Outcome measures

Outcome measures
Measure	Imipenem-Relebactam Arm n=5 Participants Patients receive imipenem/cilastatin/relebactam IV over 30-60 minutes once every 6 hours (q6h) for 2 days for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or Patients may continue on the study drug for up to 14 days. Patients may receive other additional therapy..	Standard of Care (SOC) Arm n=7 Participants Patients receive cefepime IV q8h for a minimum of 6 doses, or meropenem IV q8h for a minimum of 6 doses, or piperacillin/tazobactam IV q6h for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or orally (PO) q12h. Daptomycion could be given if no pneumonia. Patients may receive other additional therapy.
Microbiological Outcome in the ME Analysis Set at LFU. Eradication	5 Participants	6 Participants
Microbiological Outcome in the ME Analysis Set at LFU. Presumed eradication	0 Participants	1 Participants

SECONDARY outcome

Timeframe: 21 to 28 days after the start of inpatient IV study drug.

Population: Participants in MITT (Modified Intent-To-Treat) Analysis Set The MITT Analysis Set will be a subset of the ITT Analysis Set and will include all randomized patients who received any amount of inpatient IV study drug and meet minimal disease criteria (Inclusion Criterion 3). Patients will be analyzed according to randomized treatment group, regardless of treatment received.

The secondary efficacy outcome is infection-related mortality of the patients in the MITT (Modified Intent-To-Treat) Analysis Set at test-of-cure (TOC).

Outcome measures

Outcome measures
Measure	Imipenem-Relebactam Arm n=49 Participants Patients receive imipenem/cilastatin/relebactam IV over 30-60 minutes once every 6 hours (q6h) for 2 days for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or Patients may continue on the study drug for up to 14 days. Patients may receive other additional therapy..	Standard of Care (SOC) Arm n=50 Participants Patients receive cefepime IV q8h for a minimum of 6 doses, or meropenem IV q8h for a minimum of 6 doses, or piperacillin/tazobactam IV q6h for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or orally (PO) q12h. Daptomycion could be given if no pneumonia. Patients may receive other additional therapy.
Infection-related Mortality in the MITT Analysis Set at TOC.	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 35 to 42 days after the start of inpatient IV study drug.

The secondary efficacy outcome is infection-related mortality of the patients in the MITT (Modified Intent-To-Treat) Analysis Set at late follow-up (LFU).

Outcome measures

Outcome measures
Measure	Imipenem-Relebactam Arm n=49 Participants Patients receive imipenem/cilastatin/relebactam IV over 30-60 minutes once every 6 hours (q6h) for 2 days for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or Patients may continue on the study drug for up to 14 days. Patients may receive other additional therapy..	Standard of Care (SOC) Arm n=50 Participants Patients receive cefepime IV q8h for a minimum of 6 doses, or meropenem IV q8h for a minimum of 6 doses, or piperacillin/tazobactam IV q6h for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or orally (PO) q12h. Daptomycion could be given if no pneumonia. Patients may receive other additional therapy.
Infection-related Mortality in the MITT Analysis Set at LFU.	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 21 to 28 days after the start of inpatient IV study drug.

The secondary efficacy outcome is Infection-related mortality of the participants in the mMITT (Microbiological Modified Intent-To-Treat) Analysis Set at test-of-cure (TOC).

Outcome measures

Outcome measures
Measure	Imipenem-Relebactam Arm n=7 Participants Patients receive imipenem/cilastatin/relebactam IV over 30-60 minutes once every 6 hours (q6h) for 2 days for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or Patients may continue on the study drug for up to 14 days. Patients may receive other additional therapy..	Standard of Care (SOC) Arm n=12 Participants Patients receive cefepime IV q8h for a minimum of 6 doses, or meropenem IV q8h for a minimum of 6 doses, or piperacillin/tazobactam IV q6h for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or orally (PO) q12h. Daptomycion could be given if no pneumonia. Patients may receive other additional therapy.
Infection-related Mortality in the mMITT Analysis Set at TOC.	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 35 to 42 days after the start of inpatient IV study drug.

The secondary efficacy outcome is Infection-related mortality of the patients in the mMITT (Microbiological Modified Intent-To-Treat) Analysis Set at late follow-up (LFU).

Outcome measures

Outcome measures
Measure	Imipenem-Relebactam Arm n=7 Participants Patients receive imipenem/cilastatin/relebactam IV over 30-60 minutes once every 6 hours (q6h) for 2 days for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or Patients may continue on the study drug for up to 14 days. Patients may receive other additional therapy..	Standard of Care (SOC) Arm n=12 Participants Patients receive cefepime IV q8h for a minimum of 6 doses, or meropenem IV q8h for a minimum of 6 doses, or piperacillin/tazobactam IV q6h for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or orally (PO) q12h. Daptomycion could be given if no pneumonia. Patients may receive other additional therapy.
Infection-related Mortality in the mMITT Analysis Set at LFU.	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 30 days after the last dose of inpatient IV study drug.

The secondary efficacy outcome is 30-day all-cause mortality of the patients in the MITT (Modified Intent-To-Treat) Analysis Set.

Outcome measures

Outcome measures
Measure	Imipenem-Relebactam Arm n=49 Participants Patients receive imipenem/cilastatin/relebactam IV over 30-60 minutes once every 6 hours (q6h) for 2 days for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or Patients may continue on the study drug for up to 14 days. Patients may receive other additional therapy..	Standard of Care (SOC) Arm n=50 Participants Patients receive cefepime IV q8h for a minimum of 6 doses, or meropenem IV q8h for a minimum of 6 doses, or piperacillin/tazobactam IV q6h for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or orally (PO) q12h. Daptomycion could be given if no pneumonia. Patients may receive other additional therapy.
30-Day All-cause Mortality in the MITT Analysis Set.	2 Participants	3 Participants

SECONDARY outcome

Timeframe: 30 days after the last dose of inpatient IV study drug.

Population: Patients in MITT (Modified Intent-To-Treat) Analysis Set The mMITT Analysis Set will be a subset of the MITT Analysis Set and will include those patients for whom at least 1 qualifying bacterial pathogen was isolated from an appropriate microbiological specimen at baseline, irrespective of susceptibility to study therapies.

The secondary efficacy outcome is 30-day all-cause mortality of the patients in the mMITT (Microbiological Modified Intent-To-Treat) Analysis Set.

Outcome measures

Outcome measures
Measure	Imipenem-Relebactam Arm n=7 Participants Patients receive imipenem/cilastatin/relebactam IV over 30-60 minutes once every 6 hours (q6h) for 2 days for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or Patients may continue on the study drug for up to 14 days. Patients may receive other additional therapy..	Standard of Care (SOC) Arm n=12 Participants Patients receive cefepime IV q8h for a minimum of 6 doses, or meropenem IV q8h for a minimum of 6 doses, or piperacillin/tazobactam IV q6h for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or orally (PO) q12h. Daptomycion could be given if no pneumonia. Patients may receive other additional therapy.
30-Day All-cause Mortality in the mMITT Analysis Set.	0 Participants	0 Participants

Adverse Events

Imipenem-Relebactam Arm

Serious events: 30 serious events

Other events: 4 other events

Deaths: 1 deaths

Group II (Cefepime, Meropenem, Piperacillin/Tazobactam)

Serious events: 29 serious events

Other events: 7 other events

Deaths: 4 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Imipenem-Relebactam Arm n=49 participants at risk Patients receive imipenem/cilastatin/relebactam IV over 30-60 minutes once every 6 hours (q6h) for 2 days for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or Patients may continue on the study drug for up to 14 days. Patients may receive other additional therapy.	Group II (Cefepime, Meropenem, Piperacillin/Tazobactam) n=50 participants at risk Patients receive cefepime IV q8h for a minimum of 6 doses, or meropenem IV q8h for a minimum of 6 doses, or piperacillin/tazobactam IV q6h for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or orally (PO) q12h. Daptomycion could be given if no pneumonia. Patients may receive other additional therapy.
Gastrointestinal disorders Diarrhea	2.0% 1/49 • From the date of the start of inpatient IV study drug to 35 to 42 days after the start of inpatient IV study drug Per protocol, all SAEs were collected and reported according to the clinicaltrials.gov definitions. Per protocol, all AEs of any grade that are possibly, probably and definitely related to the study drug, and any AE grade 3 or above regardless of their attribution to study drug were collected and reported. Therefore, other AEs, not required per protocol, were not collected.	0.00% 0/50 • From the date of the start of inpatient IV study drug to 35 to 42 days after the start of inpatient IV study drug Per protocol, all SAEs were collected and reported according to the clinicaltrials.gov definitions. Per protocol, all AEs of any grade that are possibly, probably and definitely related to the study drug, and any AE grade 3 or above regardless of their attribution to study drug were collected and reported. Therefore, other AEs, not required per protocol, were not collected.
Gastrointestinal disorders Vomiting	4.1% 2/49 • From the date of the start of inpatient IV study drug to 35 to 42 days after the start of inpatient IV study drug Per protocol, all SAEs were collected and reported according to the clinicaltrials.gov definitions. Per protocol, all AEs of any grade that are possibly, probably and definitely related to the study drug, and any AE grade 3 or above regardless of their attribution to study drug were collected and reported. Therefore, other AEs, not required per protocol, were not collected.	0.00% 0/50 • From the date of the start of inpatient IV study drug to 35 to 42 days after the start of inpatient IV study drug Per protocol, all SAEs were collected and reported according to the clinicaltrials.gov definitions. Per protocol, all AEs of any grade that are possibly, probably and definitely related to the study drug, and any AE grade 3 or above regardless of their attribution to study drug were collected and reported. Therefore, other AEs, not required per protocol, were not collected.
Immune system disorders Allergic Reaction	2.0% 1/49 • From the date of the start of inpatient IV study drug to 35 to 42 days after the start of inpatient IV study drug Per protocol, all SAEs were collected and reported according to the clinicaltrials.gov definitions. Per protocol, all AEs of any grade that are possibly, probably and definitely related to the study drug, and any AE grade 3 or above regardless of their attribution to study drug were collected and reported. Therefore, other AEs, not required per protocol, were not collected.	2.0% 1/50 • From the date of the start of inpatient IV study drug to 35 to 42 days after the start of inpatient IV study drug Per protocol, all SAEs were collected and reported according to the clinicaltrials.gov definitions. Per protocol, all AEs of any grade that are possibly, probably and definitely related to the study drug, and any AE grade 3 or above regardless of their attribution to study drug were collected and reported. Therefore, other AEs, not required per protocol, were not collected.
Injury, poisoning and procedural complications Infusion related reaction	2.0% 1/49 • From the date of the start of inpatient IV study drug to 35 to 42 days after the start of inpatient IV study drug Per protocol, all SAEs were collected and reported according to the clinicaltrials.gov definitions. Per protocol, all AEs of any grade that are possibly, probably and definitely related to the study drug, and any AE grade 3 or above regardless of their attribution to study drug were collected and reported. Therefore, other AEs, not required per protocol, were not collected.	0.00% 0/50 • From the date of the start of inpatient IV study drug to 35 to 42 days after the start of inpatient IV study drug Per protocol, all SAEs were collected and reported according to the clinicaltrials.gov definitions. Per protocol, all AEs of any grade that are possibly, probably and definitely related to the study drug, and any AE grade 3 or above regardless of their attribution to study drug were collected and reported. Therefore, other AEs, not required per protocol, were not collected.
Investigations Alanine aminotransferase increased	0.00% 0/49 • From the date of the start of inpatient IV study drug to 35 to 42 days after the start of inpatient IV study drug Per protocol, all SAEs were collected and reported according to the clinicaltrials.gov definitions. Per protocol, all AEs of any grade that are possibly, probably and definitely related to the study drug, and any AE grade 3 or above regardless of their attribution to study drug were collected and reported. Therefore, other AEs, not required per protocol, were not collected.	8.0% 4/50 • From the date of the start of inpatient IV study drug to 35 to 42 days after the start of inpatient IV study drug Per protocol, all SAEs were collected and reported according to the clinicaltrials.gov definitions. Per protocol, all AEs of any grade that are possibly, probably and definitely related to the study drug, and any AE grade 3 or above regardless of their attribution to study drug were collected and reported. Therefore, other AEs, not required per protocol, were not collected.
Investigations Aspartate Aminotransferase Increased	2.0% 1/49 • From the date of the start of inpatient IV study drug to 35 to 42 days after the start of inpatient IV study drug Per protocol, all SAEs were collected and reported according to the clinicaltrials.gov definitions. Per protocol, all AEs of any grade that are possibly, probably and definitely related to the study drug, and any AE grade 3 or above regardless of their attribution to study drug were collected and reported. Therefore, other AEs, not required per protocol, were not collected.	2.0% 1/50 • From the date of the start of inpatient IV study drug to 35 to 42 days after the start of inpatient IV study drug Per protocol, all SAEs were collected and reported according to the clinicaltrials.gov definitions. Per protocol, all AEs of any grade that are possibly, probably and definitely related to the study drug, and any AE grade 3 or above regardless of their attribution to study drug were collected and reported. Therefore, other AEs, not required per protocol, were not collected.
Investigations Blood bilirubin increased	0.00% 0/49 • From the date of the start of inpatient IV study drug to 35 to 42 days after the start of inpatient IV study drug Per protocol, all SAEs were collected and reported according to the clinicaltrials.gov definitions. Per protocol, all AEs of any grade that are possibly, probably and definitely related to the study drug, and any AE grade 3 or above regardless of their attribution to study drug were collected and reported. Therefore, other AEs, not required per protocol, were not collected.	2.0% 1/50 • From the date of the start of inpatient IV study drug to 35 to 42 days after the start of inpatient IV study drug Per protocol, all SAEs were collected and reported according to the clinicaltrials.gov definitions. Per protocol, all AEs of any grade that are possibly, probably and definitely related to the study drug, and any AE grade 3 or above regardless of their attribution to study drug were collected and reported. Therefore, other AEs, not required per protocol, were not collected.
Investigations CPK increased	0.00% 0/49 • From the date of the start of inpatient IV study drug to 35 to 42 days after the start of inpatient IV study drug Per protocol, all SAEs were collected and reported according to the clinicaltrials.gov definitions. Per protocol, all AEs of any grade that are possibly, probably and definitely related to the study drug, and any AE grade 3 or above regardless of their attribution to study drug were collected and reported. Therefore, other AEs, not required per protocol, were not collected.	2.0% 1/50 • From the date of the start of inpatient IV study drug to 35 to 42 days after the start of inpatient IV study drug Per protocol, all SAEs were collected and reported according to the clinicaltrials.gov definitions. Per protocol, all AEs of any grade that are possibly, probably and definitely related to the study drug, and any AE grade 3 or above regardless of their attribution to study drug were collected and reported. Therefore, other AEs, not required per protocol, were not collected.
Metabolism and nutrition disorders Hypokalemia	2.0% 1/49 • From the date of the start of inpatient IV study drug to 35 to 42 days after the start of inpatient IV study drug Per protocol, all SAEs were collected and reported according to the clinicaltrials.gov definitions. Per protocol, all AEs of any grade that are possibly, probably and definitely related to the study drug, and any AE grade 3 or above regardless of their attribution to study drug were collected and reported. Therefore, other AEs, not required per protocol, were not collected.	0.00% 0/50 • From the date of the start of inpatient IV study drug to 35 to 42 days after the start of inpatient IV study drug Per protocol, all SAEs were collected and reported according to the clinicaltrials.gov definitions. Per protocol, all AEs of any grade that are possibly, probably and definitely related to the study drug, and any AE grade 3 or above regardless of their attribution to study drug were collected and reported. Therefore, other AEs, not required per protocol, were not collected.
Nervous system disorders Dysgeusia	0.00% 0/49 • From the date of the start of inpatient IV study drug to 35 to 42 days after the start of inpatient IV study drug Per protocol, all SAEs were collected and reported according to the clinicaltrials.gov definitions. Per protocol, all AEs of any grade that are possibly, probably and definitely related to the study drug, and any AE grade 3 or above regardless of their attribution to study drug were collected and reported. Therefore, other AEs, not required per protocol, were not collected.	2.0% 1/50 • From the date of the start of inpatient IV study drug to 35 to 42 days after the start of inpatient IV study drug Per protocol, all SAEs were collected and reported according to the clinicaltrials.gov definitions. Per protocol, all AEs of any grade that are possibly, probably and definitely related to the study drug, and any AE grade 3 or above regardless of their attribution to study drug were collected and reported. Therefore, other AEs, not required per protocol, were not collected.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other red rash	2.0% 1/49 • From the date of the start of inpatient IV study drug to 35 to 42 days after the start of inpatient IV study drug Per protocol, all SAEs were collected and reported according to the clinicaltrials.gov definitions. Per protocol, all AEs of any grade that are possibly, probably and definitely related to the study drug, and any AE grade 3 or above regardless of their attribution to study drug were collected and reported. Therefore, other AEs, not required per protocol, were not collected.	0.00% 0/50 • From the date of the start of inpatient IV study drug to 35 to 42 days after the start of inpatient IV study drug Per protocol, all SAEs were collected and reported according to the clinicaltrials.gov definitions. Per protocol, all AEs of any grade that are possibly, probably and definitely related to the study drug, and any AE grade 3 or above regardless of their attribution to study drug were collected and reported. Therefore, other AEs, not required per protocol, were not collected.
Skin and subcutaneous tissue disorders Rash Maculo-papular	0.00% 0/49 • From the date of the start of inpatient IV study drug to 35 to 42 days after the start of inpatient IV study drug Per protocol, all SAEs were collected and reported according to the clinicaltrials.gov definitions. Per protocol, all AEs of any grade that are possibly, probably and definitely related to the study drug, and any AE grade 3 or above regardless of their attribution to study drug were collected and reported. Therefore, other AEs, not required per protocol, were not collected.	2.0% 1/50 • From the date of the start of inpatient IV study drug to 35 to 42 days after the start of inpatient IV study drug Per protocol, all SAEs were collected and reported according to the clinicaltrials.gov definitions. Per protocol, all AEs of any grade that are possibly, probably and definitely related to the study drug, and any AE grade 3 or above regardless of their attribution to study drug were collected and reported. Therefore, other AEs, not required per protocol, were not collected.

Additional Information

Dr. Issam I Raad

The University of M.D. Anderson Cancer Center

Phone: 713-792-6237

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place