This is the classic website, which will be retired eventually. Please visit the modernized ClinicalTrials.gov instead.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    Sulbactam-durlobactam | Hospital-acquired Bacterial Pneumonia
Previous Study | Return to List | Next Study

Study to Evaluate the Efficacy and Safety of Intravenous Sulbactam-ETX2514 in the Treatment of Patients With Infections Caused by Acinetobacter Baumannii-calcoaceticus Complex (ATTACK)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03894046
Recruitment Status : Completed
First Posted : March 28, 2019
Results First Posted : February 1, 2023
Last Update Posted : February 1, 2023
Sponsor:
Information provided by (Responsible Party):
Entasis Therapeutics

Brief Summary:
This is a 2-part study, with Part A being the randomized, controlled portion of the study in patients with ABC hospital-acquired bacterial pneumonia (HABP), ventilator-associated bacterial pneumonia (VABP), or bacteremia. Part B is the single-group portion of the study and includes ABC infections that are resistant to or have failed colistin or polymyxin B treatment, as detailed in the inclusion criteria.

Condition or disease Intervention/treatment Phase
Acinetobacter Baumannii-calcoaceticus Complex Hospital-acquired Bacterial Pneumonia Ventilator-associated Bacterial Pneumonia Bacteremia Colistin Resistant ABC Drug: Sulbactam Drug: Durlobactam Drug: Colistin Drug: Imipenem/Cilastatin 500 mg/500 mg Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 207 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Masking Description: Study drugs will not be masked due to logistical reasons, every attempt will be made to maintain the blind for patients, all staff at the site, and the Sponsor or its designees, except for the treatment physician and other immediate healthcare providers.
Primary Purpose: Treatment
Official Title: A Randomized, Active-controlled Study to Evaluate the Efficacy and Safety of Intravenous Sulbactam-ETX2514 in the Treatment of Patients With Infections Caused by Acinetobacter Baumannii-calcoaceticus Complex
Actual Study Start Date : September 5, 2019
Actual Primary Completion Date : July 26, 2021
Actual Study Completion Date : July 26, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Part A - Group 1

Part A was the pivotal, assessor-blind, randomized, comparative portion of the study in patients with documented ABC hospital-acquired bacterial pneumonia (HABP), ventilator-associated bacterial pneumonia (VABP), ventilated pneumonia (VP), or bacteremia.

Part A - Group 1 (experimental): 1.0 g sulbactam/1.0 g durlobactam IV infused over 3 hours every 6 hours (q6h) plus 1.0 g imipenem/1.0 g cilastatin IV infused over 1 hour q6h

Drug: Sulbactam
1.0 g sulbactam IV infused over 3 hours every 6 hours (q6h).

Drug: Durlobactam

1.0 g durlobactam IV infused over 3 hours every 6 hours (q6h).

Sulbactam-Durlobactam: Treatment for 7 days up to 14 days if clinically indicated.

Other Name: ETX2514

Drug: Imipenem/Cilastatin 500 mg/500 mg
1.0 g imipenem/1.0 g cilastatin IV infused over 1 hour q6h. Treatment for 7 days up to 14 days if clinically indicated.

Active Comparator: Part A - Group 2
Part A - Group 2 (control group): 2.5 mg/kg colistin IV infused over 30 minutes every 12 hours (after an initial loading dose of colistin 2.5 to 5 mg/kg) plus 1.0 g imipenem/1.0 g cilastatin IV infused over 1 hour q6h.
Drug: Colistin
Treatment for 7 days up to 14 days if clinically indicated.
Other Name: COLOMYCIN INJECTION 2 million IU/vial

Drug: Imipenem/Cilastatin 500 mg/500 mg
1.0 g imipenem/1.0 g cilastatin IV infused over 1 hour q6h. Treatment for 7 days up to 14 days if clinically indicated.

Experimental: Part B - Group 3

Part B (Group 3) was the open-label, supportive portion of the study that included patients known to have HABP, VABP, VP, and/or bacteremia infections associated with ABC organisms resistant to colistin or polymyxin B, who failed a colistin or polymyxin B regimen prior to study entry or were on acute renal replacement therapy, and patients with infections due to colistin- or polymyxin B-resistant ABC with sources of infection other than HABP, VABP, VP, and/or bacteremia.

Part B - Group 3: 1.0 g ETX2514/1.0 g sulbactam IV infused over 3 hours q6h plus 1.0 g imipenem/1.0 g cilastatin IV infused over 1 hour q6h.

Drug: Sulbactam
1.0 g sulbactam IV infused over 3 hours every 6 hours (q6h).

Drug: Durlobactam

1.0 g durlobactam IV infused over 3 hours every 6 hours (q6h).

Sulbactam-Durlobactam: Treatment for 7 days up to 14 days if clinically indicated.

Other Name: ETX2514

Drug: Imipenem/Cilastatin 500 mg/500 mg
1.0 g imipenem/1.0 g cilastatin IV infused over 1 hour q6h. Treatment for 7 days up to 14 days if clinically indicated.




Primary Outcome Measures :
  1. Proportion of Patients With All-Cause Mortality in CRABC m-MITT Population [ Time Frame: 28 Days ]
    The primary efficacy endpoint for the study is 28-day all-cause mortality in the CRABC m-MITT population in Part A.

  2. Proportion of Patients With Nephrotoxicity [ Time Frame: 28 days ]
    The primary safety endpoint for the study is nephrotoxicity, as measured by the Risk-Injury-Failure-Loss-End-stage renal disease (RIFLE) criteria, in the MITT population in Part A.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

PART A

  1. A confirmed diagnosis of a serious infection that will require treatment with IV antibiotics;
  2. A known infection caused by ABC (bacteremia, HABP, VABP, VP, cUTI or AP, or surgical or post-traumatic wound infections) as either a single pathogen or member of a polymicrobial infection based on evidence from culture or, if available, rapid diagnostic test from a sample collected within 72 hours prior to randomization (HABP/VABP/VP patients), AND 1 of the following:

    1. Has received no more than 48 hrs of potentially effective (ie, Gram negative coverage) antimicrobial therapy prior to the first dose of study drug;
    2. Is clinically failing prior treatment regimens
  3. APACHE II score 10 and 30 inclusive, or SOFA score between 7 and 11 inclusive, at time of diagnosis
  4. Expectation, in the judgment of the Investigator, that the patient will benefit from effective antibiotic therapy and appropriate supportive care for the anticipated duration of the study
  5. Women of childbearing potential (ie, not post-menopausal or surgically sterilized) must have a negative highly sensitive urine or serum pregnancy test before randomization. Participating women of childbearing potential must be willing to consistently use one highly effective method of contraception (ie, condom, combined oral contraceptive, implant, injectable, indwelling intrauterine device, or a vasectomized partner) from Screening until at least 30 days after administration of the last dose of study drug.

PART B

1. Has an infection (HABP, VABP, VP, bacteremia, cUTI, AP, or surgical or post-traumatic wound infections) caused by ABC organisms known to be resistant to colistin (defined as MIC ≥4 mg/L by a non-agar based method);

  1. Known to be resistant to colistin or polymyxin B; or
  2. Known intolerance to colistin; or
  3. Has myasthenia gravis or another neuromuscular syndrome(s) that contraindicates colistin and is not ventilated; or
  4. Has acute kidney injury and is receiving renal replacement therapy at study entry.

Exclusion Criteria:

  1. Evidence of active concurrent pneumonia requiring additional antimicrobial treatment
  2. Presence of suspected or confirmed deep seated bacterial infections such as bacterial Gram negative osteomyelitis, endocarditis, or meningitis requiring prolonged therapy, as determined by history and/or physical examination;
  3. Sustained shock with persisting hypotension requiring vasopressors to maintain mean arterial pressure (MAP) ≥ 60 mmHg;
  4. Pregnant or breastfeeding women;
  5. Receiving peritoneal dialysis;
  6. Requirement for continuing treatment with probenecid, methotrexate, ganciclovir, valproic acid, or divalproex sodium during the study;
  7. Evidence of significant hepatic disease or dysfunction, including known acute viral hepatitis, hepatic cirrhosis, hepatic failure, chronic ascites, or hepatic encephalopathy;

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03894046


Locations
Show Show 92 study locations
Sponsors and Collaborators
Entasis Therapeutics
  Study Documents (Full-Text)

Documents provided by Entasis Therapeutics:
Study Protocol  [PDF] December 17, 2020
Statistical Analysis Plan  [PDF] June 22, 2021

Layout table for additonal information
Responsible Party: Entasis Therapeutics
ClinicalTrials.gov Identifier: NCT03894046    
Other Study ID Numbers: CS2514-2017-0004
First Posted: March 28, 2019    Key Record Dates
Results First Posted: February 1, 2023
Last Update Posted: February 1, 2023
Last Verified: January 2023

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Pneumonia
Pneumonia, Bacterial
Bacterial Infections
Bacterial Infections and Mycoses
Gram-Negative Bacterial Infections
Bacteremia
Acinetobacter Infections
Infections
Respiratory Tract Infections
Lung Diseases
Respiratory Tract Diseases
Sepsis
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Moraxellaceae Infections
Imipenem
Colistin
Sulbactam
Durlobactam
Cilastatin
Anti-Bacterial Agents
Anti-Infective Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
beta-Lactamase Inhibitors