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Acinetobacter Baumannii-calcoaceticus ComplexPhase 3ATTACKNCT03894046

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

A Phase 3 study testing Sulbactam, Durlobactam and Colistin in people with Acinetobacter Baumannii-calcoaceticus Complex and Hospital-acquired Bacterial Pneumonia, run by Entasis Therapeutics at 90 sites in 17 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Sulbactam, Durlobactam and Colistin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
207 participants
Where
90 sitesin 17 countries
Study dates
5 Sep 2019to 26 Jul 2021
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • PART A
  • A confirmed diagnosis of a serious infection that will require treatment with IV antibiotics;
  • 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:
  • Has received no more than 48 hrs of potentially effective (ie, Gram negative coverage) antimicrobial therapy prior to the first dose of study drug;
  • Is clinically failing prior treatment regimens
  • APACHE II score 10 and 30 inclusive, or SOFA score between 7 and 11 inclusive, at time of diagnosis
Show all 14Show fewer
  • 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
  • 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);
  • Known to be resistant to colistin or polymyxin B; or
  • Known intolerance to colistin; or
  • Has myasthenia gravis or another neuromuscular syndrome(s) that contraindicates colistin and is not ventilated; or
  • Has acute kidney injury and is receiving renal replacement therapy at study entry.

Who cannot join

  • Evidence of active concurrent pneumonia requiring additional antimicrobial treatment
  • 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;
  • Sustained shock with persisting hypotension requiring vasopressors to maintain mean arterial pressure (MAP) ≥ 60 mmHg;
  • Pregnant or breastfeeding women;
  • Receiving peritoneal dialysis;
  • Requirement for continuing treatment with probenecid, methotrexate, ganciclovir, valproic acid, or divalproex sodium during the study;
  • Evidence of significant hepatic disease or dysfunction, including known acute viral hepatitis, hepatic cirrhosis, hepatic failure, chronic ascites, or hepatic encephalopathy;

Trial locations and contacts

90 sites in 17 countries.

90 sites in 17 countries

China18 sites
  • Entasis Research Site 1

    Beijing

  • Entasis Research Site 2

    Beijing

  • Entasis Research Site 3

    Beijing

  • Entasis Research Site

    Changsha

  • Entasis Research Site

    Chongqing

  • Entasis Research Site

    Guangzhou

  • Entasis Research Site

    Hebei

  • Entasis Research Site 1

    Hefei

  • Entasis Research Site 2

    Hefei

  • Entasis Research Site

    Hubei

  • Entasis Research Site

    Nanchang

  • Entasis Research Site

    Nanjing

  • Entasis Research Site

    Nanning

  • Entasis Research Site 1

    Shanghai

  • Entasis Research Site 2

    Shanghai

  • Entasis Research Site

    Shenzhen

  • Entasis Research Site

    Tianjin

  • Entasis Research Site

    Wuhan

Other trials in China

Russia9 sites
  • Entasis Research Site

    Arkhangelsk

  • Entasis Research Site

    Krasnodar

  • Entasis Research Site 1

    Novosibirsk

  • Entasis Research Site 2

    Novosibirsk

  • Entasis Research Site 3

    Novosibirsk

  • Entasis Research Site 2

    Saint Petersburg, 192242

  • Entasis Research Site

    Smolensk

  • Entasis Research Site 1

    Tomsk

  • Entasis Research Site 2

    Tomsk

Other trials in Russia

India7 sites
  • Entasis Research Site

    Ahmedabad

  • Entasis Research Site

    Belagavi

  • Entasis Research Site 2

    Gujrāt, 382 428

  • Entasis Research Site 1

    Gujrāt, 395002

  • Entasis Research Site

    Hyderabad

  • Entasis Research Site

    Kolkata

  • Entasis Research Site

    Pune

Other trials in India

Turkey (Türkiye)6 sites
  • Entasis Research Site 1

    Ankara

  • Entasis Research Site 2

    Ankara

  • Entasis Research Site

    Eskişehir

  • Entasis Research Site

    Kocaeli

  • Entasis Research Site

    Küçükçekmece

  • Entasis Research Site

    Trabzon

Other trials in Turkey (Türkiye)

United States5 sites
  • Entasis Research Site

    Chicago, Illinois, 60611

  • Entasis Research Site

    Cincinnati, Ohio, 45219

  • Entasis Research Site

    Houston, Texas, 77030

  • Entasis Research Site

    Memphis, Tennessee, 38163

  • Entasis Research Site

    Shreveport, Louisiana, 71101

Other trials in United States

Brazil5 sites
  • Entasis Research Site

    Belo Horizonte

  • Entasis Research Site

    Campinas

  • Entasis Research Site

    Porto Alegre

  • Entasis Research Site

    Salvador

  • Entasis Research Site

    São José do Rio Preto

Other trials in Brazil

Greece5 sites
  • Entasis Research Site 1

    Athens

  • Entasis Research Site 3

    Athens

  • Entasis Research Site

    Heraklion

  • Entasis Research Site

    Larissa

  • Entasis Research Site

    Thessaloniki

Other trials in Greece

Mexico5 sites
  • Entasis Research Site 1

    Guadalajara

  • Entasis Research Site 2

    Guadalajara

  • Entasis Research Site

    Mexico City

  • Entasis Research Site

    Monterrey

  • Entasis Research Site

    San Luis Potosí City

Other trials in Mexico

Peru5 sites
  • Entasis Research Site

    Bellavista

  • Entasis Research Site

    Cusco

  • Entasis Research Site

    Lima

  • Entasis Research Site

    San Isidro

  • Entasis Research Site

    San Martín de Porres

Other trials in Peru

Belarus4 sites
  • Entasis Research Site

    Brest

  • Entasis Research Site

    Grodno

  • Entasis Research Site

    Homyel

  • Entasis Research Site

    Minsk

Other trials in Belarus

Israel4 sites
  • Entasis Research Site

    Holon

  • Entasis Research Site

    Tel Aviv

  • Entasis Research Site

    Tel HaShomer

  • Entasis Research Site

    Tsrifin

Other trials in Israel

Thailand4 sites
  • Entasis Research Site

    Chiang Mai

  • Entasis Research Site

    Khon Kaen

  • Entasis Research Site

    Nakhon Ratchasima

  • Entasis Research Site

    Nonthaburi

Other trials in Thailand

Hungary3 sites
  • Entasis Research Site 1

    Budapest

  • Entasis Research Site 2

    Budapest

  • Entasis Research Site

    Debrecen

Other trials in Hungary

Lithuania3 sites
  • Entasis Research Site

    Kaunas

  • Entasis Research Site

    Klaipėda

  • Entasis Research Site

    Vilnius

Other trials in Lithuania

South Korea3 sites
  • Entasis Research Site

    Gyeonggi-do

  • Entasis Research Site 1

    Seoul

  • Entasis Research Site 2

    Seoul

Other trials in South Korea

Taiwan3 sites
  • Entasis Research Site

    Kaohsiung City

  • Entasis Research Site

    Taichung

  • Entasis Research Site

    Taipei

Other trials in Taiwan

Puerto Rico1 site
  • Entasis Research Site

    Ponce

Other trials in Puerto Rico

About this study

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

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.

Being tested
Sulbactam, Durlobactam, Colistin, Imipenem/Cilastatin 500 mg/500 mg
Medical subject headings
Bacteremia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SulbactamDrug

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

  • DurlobactamDrug

    Also called ETX2514

    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.

  • ColistinDrug

    Also called COLOMYCIN INJECTION 2 million IU/vial

    Treatment for 7 days up to 14 days if clinically indicated.

  • Imipenem/Cilastatin 500 mg/500 mgDrug

    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.

Study groups in NCT03894046
Study groupRoleWhat they receive
Part A - Group 1ExperimentalPart 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
Receives: Drug: Sulbactam; Drug: Durlobactam; Drug: Imipenem/Cilastatin 500 mg/500 mg
Part A - Group 2Active comparatorPart 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.
Receives: Drug: Colistin; Drug: Imipenem/Cilastatin 500 mg/500 mg
Part B - Group 3ExperimentalPart 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.
Receives: Drug: Sulbactam; Drug: Durlobactam; Drug: Imipenem/Cilastatin 500 mg/500 mg

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Proportion of Patients With All-Cause Mortality in CRABC m-MITT Population

    The primary efficacy endpoint for the study is 28-day all-cause mortality in the CRABC m-MITT population in Part A.

    Measured: 28 Days

  2. Proportion of Patients With Nephrotoxicity

    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.

    Measured: 28 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Mar 2019
  2. Study start5 Sep 2019
  3. Primary completion26 Jul 2021
  4. Study completion26 Jul 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
207 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03894046
Sponsor's protocol ID
CS2514-2017-0004
Acronym
ATTACK
Status last verified
Jan 2023
First submitted
27 Mar 2019
Last updated
1 Feb 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Kaye KS, Shorr AF, Wunderink RG, Du B, Poirier GE, Rana K, Miller A, Lewis D, O'Donnell J, Chen L, Reinhart H, Srinivasan S, Isaacs R, Altarac D. Efficacy and safety of sulbactam-durlobactam versus colistin for the treatment of patients with serious infections caused by Acinetobacter baumannii-calcoaceticus complex: a multicentre, randomised, active-controlled, phase 3, non-inferiority clinical trial (ATTACK). Lancet Infect Dis. 2023 Sep;23(9):1072-1084. doi: 10.1016/S1473-3099(23)00184-6. Epub 2023 May 11.

    PubMed 37182534

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Sulbactam, Durlobactam and Colistin in people with Acinetobacter Baumannii-calcoaceticus Complex and Hospital-acquired Bacterial Pneumonia, run by Entasis Therapeutics at 90 sites in 17 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 90 sites in China, Russia, India, Turkey (Türkiye), United States and 12 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Feb 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of Patients With All-Cause Mortality in CRABC m-MITT Population (time frame: 28 Days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03894046, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Feb 2023.

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