CClinicalTrials.gg
CompletedNCT03293485Updated Feb 12, 2021Results posted

Efficacy and Safety of Imipenem+Cilastatin/Relebactam (MK-7655A) in Japanese Participants With Complicated Intra-abdominal Infection or Complicated Urinary Tract Infection (MK-7655A-017)

A Phase 3 interventional study of Imipenem+Cilastatin/Relebactam in Complicated Intra-abdominal Infection and Complicated Urinary Tract Infection, sponsored by Merck Sharp & Dohme LLC. Completed at 29 sites in Japan. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-02-12.

Sponsored by Merck Sharp & Dohme LLC · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
83
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study summary

The study will evaluate the efficacy and safety of imipenem+cilastatin/relebactam (IMI/REL, MK-7655A) in Japanese participants with complicated intra-abdominal infection (cIAI) or complicated urinary tract infection (cUTI).

02

Conditions studied

  • Complicated Intra-abdominal Infection
  • Complicated Urinary Tract Infection
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • requires hospitalization and treatment with IV antibiotic therapy for complicated intraabdominal infection (cIAI) or complicated urinary tract infection (cUTI). Per-protocol diagnostic criteria apply to the qualifying infection types.
  • infection is known or thought to be caused by microorganisms susceptible to the IV study therapy
  • baseline specimen for primary infection site culture obtained at operative procedure in Screening period or at Baseline for cIAI participants, and within 48 hours before initiation of IV study drug for cUTI participants
  • female or male who is not of reproductive potential, or female or male who is of reproductive potential and agrees to avoid becoming pregnant or impregnating a partner from the time of consent through completion of the study, by practicing abstinence from heterosexual activity or using acceptable contraception during heterosexual activity.

Exclusion criteria

Exclusion Criteria:

  • received any amount of effective antibiotic therapy after obtaining the culture for admission to the study and before administration of the first dose of IV study therapy
  • received treatment with systemic effective antibiotics for >24 hours within the 72 hours before initiation of study therapy
  • has a concurrent infection, including endocarditis, osteomyelitis, meningitis, or prosthetic joint infection, that would interfere with evaluation of response to IMI/REL
  • has a cIAI or cUTI due to a confirmed fungal pathogen
  • has a cUTI that meets any of the following: 1) complete obstruction of any portion of the urinary tract, 2) known ileal loop, 3) intractable vesico-ureteral reflux, 4) presence of indwelling urinary catheter which cannot be removed at study entry
  • has a cIAI that meets any of the following: 1) infection that should be managed by Staged Abdominal Repair (STAR) or open abdomen therapy, 2) infection limited to the hollow viscus
  • history of serious allergy, hypersensitivity, or any serious reaction to any carbapenem, cephalosporin, penicillin or other beta-lactam agent, or other beta-lactamase inhibitors
  • female who is pregnant or is expecting to conceive, is breastfeeding, or plans to breastfeed before completion of the study
  • history of a seizure disorder
  • anticipates to be treated with valproic acid, concomitant IV or an oral antimicrobial considered effective to the index pathogen, in addition to the study treatment
  • is receiving immunosuppressive therapy, including high-dose corticosteroids
  • is undergoing hemodialysis or peritoneal dialysis
  • participated in any other clinical study involving an investigational or experimental medication during the previous 30 days before Screening.
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
83 participants (actual)

Study arms

  • Experimental
    Imipenem+Cilastatin/Relebactam

    Participants with cIAI or cUTI will receive imipenem+cilastatin/relebactam intravenous (IV) infusion once every 6 hours for 5 to 14 days

    Drug: Imipenem+Cilastatin/Relebactam

Interventions

  • DrugImipenem+Cilastatin/Relebactam

    Imipenem+Cilastatin/Relebactam 200/100 mg to 500/250 mg, depending on renal function, 30-minute IV infusion once every 6 hours

    Also known as: IMI/REL, MK-7655A

05

What researchers measure

Primary outcomes

  1. Percentage of Participants Experiencing ≥1 Adverse Events (AE)

    The percentage of participants experiencing ≥1 AE was calculated. An AE was defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy could be determined.

    Time frame: Up to 28 days

  2. Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)

    The percentage of participants who discontinued from study medication due to an adverse event was calculated. An AE was defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy could be determined.

    Time frame: Up to 14 days (End of Therapy Visit)

  3. Percentage of Complicated Intra-Abdominal Infection (cIAI) Participants With Favorable Clinical Response at End of Therapy Visit

    The percentage of participants with cIAI who display a favorable clinical response at End of Therapy visit was presented. Per protocol, a subset of the cIAI/cUTI study arm was analyzed: only participants with cIAI were evaluated because clinical response is primarily relevant to cIAI. Favorable clinical response is a rating of "cure" or "improved" as determined by the investigator at the End of Therapy Visit. "Cure" is defined as: all pretherapy signs and symptoms of the index infection(s) have resolved (or returned to preinfection status) AND no additional intravenous antibiotic therapy is required AND no unplanned surgical or percutaneous drainage procedures have been performed. "Improved" is defined as: All or most pretherapy signs and symptoms of the index infection(s) have improved or resolved (or returned to preinfection status) AND no additional intravenous antibiotic therapy is required AND no unplanned surgical or percutaneous drainage procedures have been performed.

    Time frame: Between Day 5 and Day 14 (End of Therapy Visit)

  4. Percentage of Complicated Urinary Tract Infection (cUTI) Participants With Favorable Overall Microbiological Response at End of Therapy Visit

    The percentage of participants with cUTI who display a favorable Overall Microbiological Response at the End of Therapy visit was calculated. Per protocol, only a subset of the cIAI/cUTI study arm was analyzed: only participants with cUTI were evaluated because the microbiological response evaluation is primarily relevant to cUTI. A favorable Overall Microbiological Response is defined as a urine culture taken at the End of Therapy Visit showing eradication (e.g., ≥10\^5 CFU/mL is reduced to \<10\^4 CFU/mL) of all uropathogens found at study entry.

    Time frame: Between Day 5 and Day 14 (End of Therapy Visit)

Secondary outcomes

  1. Percentage of Complicated Intra-Abdominal Infection (cIAI) Participants With Favorable Clinical Response at Test of Cure Visit

    The percentage of participants with cIAI who display a favorable Clinical Response at the Test of Cure visit was calculated. Per protocol, only a subset of the cIAI/cUTI study arm was analyzed: only participants with cIAI were evaluated because the clinical response evaluation is primarily relevant to cIAI. A favorable clinical response is a rating of "cure" as determined by the investigator at the Test of Cure Visit. "Cure" is defined as: all pretherapy signs and symptoms of the index infection(s) have resolved (or returned to "preinfection status") AND no additional intravenous antibiotic therapy is required AND no unplanned surgical or percutaneous drainage procedures have been performed.

    Time frame: Between Day 10 and Day 23 (Test of Cure Visit)

  2. Percentage of Complicated Urinary Tract Infection (cUTI) Participants With Favorable Overall Microbiological Response at Test of Cure Visit

    The percentage of participants with cUTI who display a favorable Overall Microbiological Response at the Test of Cure visit was calculated. Per protocol, only a subset of the cIAI/cUTI study arm was analyzed: only participants with cUTI were evaluated because the microbiological response evaluation is primarily relevant to cUTI. A favorable Overall Microbiological Response is defined as a urine culture taken at the Test of Cure visit still showing eradication (e.g., ≥10\^5 CFU/mL is reduced to \<10\^4 CFU/mL) of all uropathogens found at study entry.

    Time frame: Between Day 10 and Day 23 (Test of Cure Visit)

06

Results

Posted Sep 17, 2019

Participant flow

Participant flow — Overall Study
MilestonecIAI/cUTI
Started83
Treated81
Completed78
Not completed5
Withdrew: Death1
Withdrew: Screen failure2
Withdrew: Withdrawal by subject2

Outcome measures

PrimaryPercentage of Participants Experiencing ≥1 Adverse Events (AE)

The percentage of participants experiencing ≥1 AE was calculated. An AE was defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy could be determined.

Time frame:
Up to 28 days
Reported as:
Number · Percentage of Participants
Percentage of Participants Experiencing ≥1 Adverse Events (AE)
Percentage of ParticipantscIAI/cUTI
Percentage of Participants Experiencing ≥1 Adverse Events (AE)74.1 (63.5 to 82.4)
PrimaryPercentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)

The percentage of participants who discontinued from study medication due to an adverse event was calculated. An AE was defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy could be determined.

Time frame:
Up to 14 days (End of Therapy Visit)
Reported as:
Number · Percentage of Participants
Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)
Percentage of ParticipantscIAI/cUTI
Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)4.9 (1.6 to 12.4)
PrimaryPercentage of Complicated Intra-Abdominal Infection (cIAI) Participants With Favorable Clinical Response at End of Therapy Visit

The percentage of participants with cIAI who display a favorable clinical response at End of Therapy visit was presented. Per protocol, a subset of the cIAI/cUTI study arm was analyzed: only participants with cIAI were evaluated because clinical response is primarily relevant to cIAI. Favorable clinical response is a rating of "cure" or "improved" as determined by the investigator at the End of Therapy Visit. "Cure" is defined as: all pretherapy signs and symptoms of the index infection(s) have resolved (or returned to preinfection status) AND no additional intravenous antibiotic therapy is required AND no unplanned surgical or percutaneous drainage procedures have been performed. "Improved" is defined as: All or most pretherapy signs and symptoms of the index infection(s) have improved or resolved (or returned to preinfection status) AND no additional intravenous antibiotic therapy is required AND no unplanned surgical or percutaneous drainage procedures have been performed.

Time frame:
Between Day 5 and Day 14 (End of Therapy Visit)
Reported as:
Number · Percentage of Participants
Percentage of Complicated Intra-Abdominal Infection (cIAI) Participants With Favorable Clinical Response at End of Therapy Visit
Percentage of ParticipantscIAI
Percentage of Complicated Intra-Abdominal Infection (cIAI) Participants With Favorable Clinical Response at End of Therapy Visit85.7 (67.9 to 94.9)
PrimaryPercentage of Complicated Urinary Tract Infection (cUTI) Participants With Favorable Overall Microbiological Response at End of Therapy Visit

The percentage of participants with cUTI who display a favorable Overall Microbiological Response at the End of Therapy visit was calculated. Per protocol, only a subset of the cIAI/cUTI study arm was analyzed: only participants with cUTI were evaluated because the microbiological response evaluation is primarily relevant to cUTI. A favorable Overall Microbiological Response is defined as a urine culture taken at the End of Therapy Visit showing eradication (e.g., ≥10\^5 CFU/mL is reduced to \<10\^4 CFU/mL) of all uropathogens found at study entry.

Time frame:
Between Day 5 and Day 14 (End of Therapy Visit)
Reported as:
Number · Percentage of Participants
Percentage of Complicated Urinary Tract Infection (cUTI) Participants With Favorable Overall Microbiological Response at End of Therapy Visit
Percentage of ParticipantscUTI
Percentage of Complicated Urinary Tract Infection (cUTI) Participants With Favorable Overall Microbiological Response at End of Therapy Visit100 (89.3 to 100.0)
SecondaryPercentage of Complicated Intra-Abdominal Infection (cIAI) Participants With Favorable Clinical Response at Test of Cure Visit

The percentage of participants with cIAI who display a favorable Clinical Response at the Test of Cure visit was calculated. Per protocol, only a subset of the cIAI/cUTI study arm was analyzed: only participants with cIAI were evaluated because the clinical response evaluation is primarily relevant to cIAI. A favorable clinical response is a rating of "cure" as determined by the investigator at the Test of Cure Visit. "Cure" is defined as: all pretherapy signs and symptoms of the index infection(s) have resolved (or returned to "preinfection status") AND no additional intravenous antibiotic therapy is required AND no unplanned surgical or percutaneous drainage procedures have been performed.

Time frame:
Between Day 10 and Day 23 (Test of Cure Visit)
Reported as:
Number · Percentage of Participants
Percentage of Complicated Intra-Abdominal Infection (cIAI) Participants With Favorable Clinical Response at Test of Cure Visit
Percentage of ParticipantscIAI
Percentage of Complicated Intra-Abdominal Infection (cIAI) Participants With Favorable Clinical Response at Test of Cure Visit82.1 (63.9 to 92.6)
SecondaryPercentage of Complicated Urinary Tract Infection (cUTI) Participants With Favorable Overall Microbiological Response at Test of Cure Visit

The percentage of participants with cUTI who display a favorable Overall Microbiological Response at the Test of Cure visit was calculated. Per protocol, only a subset of the cIAI/cUTI study arm was analyzed: only participants with cUTI were evaluated because the microbiological response evaluation is primarily relevant to cUTI. A favorable Overall Microbiological Response is defined as a urine culture taken at the Test of Cure visit still showing eradication (e.g., ≥10\^5 CFU/mL is reduced to \<10\^4 CFU/mL) of all uropathogens found at study entry.

Time frame:
Between Day 10 and Day 23 (Test of Cure Visit)
Reported as:
Number · Percentage of Participants
Percentage of Complicated Urinary Tract Infection (cUTI) Participants With Favorable Overall Microbiological Response at Test of Cure Visit
Percentage of ParticipantscUTI
Percentage of Complicated Urinary Tract Infection (cUTI) Participants With Favorable Overall Microbiological Response at Test of Cure Visit59.0 (43.4 to 72.9)

Adverse events

Collected over Up to 28 days (up to 14 days after completion of intravenous study therapy). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
cIAI/cUTI1/81 (1.2%)9/81 (11.1%)18/81 (22.2%)
Most frequent serious events
Most frequent serious events
EventcIAI/cUTI
Abdominal abscessInfections and infestations2/81
Rhegmatogenous retinal detachmentEye disorders1/81
Large intestine perforationGastrointestinal disorders1/81
Pancreatitis acuteGastrointestinal disorders1/81
Cholecystitis acuteHepatobiliary disorders1/81
Pelvic abscessInfections and infestations1/81
PeritonitisInfections and infestations1/81
Postoperative ileusInjury, poisoning and procedural complications1/81
Acute kidney injuryRenal and urinary disorders1/81
Renal haematomaRenal and urinary disorders1/81
Most frequent other events
Most frequent other events
EventcIAI/cUTI
DiarrhoeaGastrointestinal disorders7/81
NauseaGastrointestinal disorders7/81
NasopharyngitisInfections and infestations5/81

Baseline characteristics

Age, Continuous
Age, Continuous(Years)cIAI/cUTI
Mean62.8 ± 18.2
Sex: Female, Male
Sex: Female, Male(Participants)cIAI/cUTI
Female45
Male38
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)cIAI/cUTI
Hispanic or Latino0
Not Hispanic or Latino83
Unknown or Not Reported0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)cIAI/cUTI
American Indian or Alaska Native0
Asian83
Native Hawaiian or Other Pacific Islander0
Black or African American0
White0
More than one race0
Unknown or Not Reported0
Infection Type
Infection Type(Participants)cIAI/cUTI
cIAI39
cUTI44
07

Study locations

29 sites
  • Nagoya Ekisaikai Hospital ( Site 1724)
    Nagoya, Aichi 454-8502, Japan
  • Toyota Memorial Hospital ( Site 1708)
    Toyota, Aichi 471-8513, Japan
  • Medical Corporation Chiyukai Fukuoka Shin Mizumaki Hospital ( Site 1710)
    Onga-gun, Fukuoka 807-0051, Japan
  • Shin Yukuhashi Hospital ( Site 1722)
    Yukuhashi, Fukuoka 824-0026, Japan
  • National Hospital Organization Fukuyama Medical Center ( Site 1706)
    Fukuyama, Hiroshima 720-8520, Japan
  • Fukuyama City Hospital ( Site 1721)
    Fukuyama, Hiroshima 721-8511, Japan
  • KKR Sapporo Medical Center ( Site 1728)
    Sapporo, Hokkaido 062-0931, Japan
  • Sano Hospital ( Site 1701)
    Kobe, Hyogo 655-0031, Japan
  • National Hospital Organization Mito Medical Center ( Site 1729)
    Higashiibaraki-gun, Ibaraki 311-3193, Japan
  • Medical Corporation Tokushukai Koga General Hospital ( Site 1712)
    Koga, Ibaraki 306-0041, Japan
  • Ishikawa Prefectural Central Hospital ( Site 1707)
    Kanazawa, Ishikawa 920-8530, Japan
  • National Hospital Organization Kanazawa Medical Center ( Site 1716)
    Kanazawa, Ishikawa 920-8650, Japan
  • Kawahara Clinic ( Site 1719)
    Aira, Kagoshima 899-5431, Japan
  • National Hospital Organization Yokohama Medical Center ( Site 1702)
    Yokohama, Kanagawa 245-8575, Japan
  • National Hospital Organization Mie Chuo Medical Center ( Site 1727)
    Tsu, Mie 514-1101, Japan
  • Japan Labour Health And Safety Organization Tohoku Rosai Hospital ( Site 1714)
    Sendai, Miyagi 981-8563, Japan
  • National Hospital Organization Sendai Medical Center ( Site 1723)
    Sendai, Miyagi 983-8520, Japan
  • Suwa Red Cross Hospital ( Site 1705)
    Suwa, Nagano 392-8510, Japan
  • National Hospital Organization Nagasaki Medical Center ( Site 1718)
    Omura, Nagasaki 856-8562, Japan
  • National Hospital Organization Osaka Minami Medical Center ( Site 1715)
    Kawachinagano, Osaka 586-8521, Japan
  • National Hospital Organization Utsunomiya National Hospital ( Site 1711)
    Utsunomiya, Tochigi 329-1193, Japan
  • National Hospital Organization Minami Wakayama Medical Center ( Site 1725)
    Tanabe, Wakayama 646-8558, Japan
  • Yamanashi Prefectural Central Hospital ( Site 1703)
    Kofu, Yamanashi 400-8506, Japan
  • Fukuiken Saiseikai Hospital ( Site 1704)
    Fukui, 918-8503, Japan
  • Medical Corporation Chiyukai Fukuoka Wajiro Hospital ( Site 1709)
    Fukuoka, 811-0213, Japan
  • Medical Corporation Shingenkai Kawahara Urological Clinic ( Site 1726)
    Kagoshima, 890-0073, Japan
  • Medical Corporation Seifukai Yagi Clinic ( Site 1720)
    Kagoshima, 891-0105, Japan
  • National Hospital Organization Kumamoto Medical Center ( Site 1713)
    Kumamoto, 860-0008, Japan
  • National Hospital Organization Oita Medical Center ( Site 1717)
    Oita, 870-0263, Japan
08

References and documents

Publications

  • Kohno S, Bando H, Yoneyama F, Kikukawa H, Kawahara K, Shirakawa M, Aoyama N, Brown M, Paschke A, Takase A. The safety and efficacy of relebactam/imipenem/cilastatin in Japanese patients with complicated intra-abdominal infection or complicated urinary tract infection: A multicenter, open-label, noncomparative phase 3 study. J Infect Chemother. 2021 Feb;27(2):262-270. doi: 10.1016/j.jiac.2020.09.032. Epub 2020 Nov 13. PubMed 33191112 ↗

Study documents

  • Protocol and statistical analysis plan · May 18, 2017

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

09

Registry details

Key details

Study ID
NCT03293485
Lead sponsor
Merck Sharp & Dohme LLC
Responsible party
Sponsor
First posted
Sep 26, 2017
Start date
Oct 4, 2017
Primary completion
Sep 14, 2018
Completion
Sep 14, 2018
Results posted
Sep 17, 2019
Last update
Feb 12, 2021

Study contacts

Medical Director
study director · Merck Sharp & Dohme LLC

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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