ClinicalTrials.gg
CompletedNCT03894046ATTACKUpdated Feb 1, 2023Results posted

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 interventional study of Sulbactam and Durlobactam in Acinetobacter Baumannii-calcoaceticus Complex, Hospital-acquired Bacterial Pneumonia and Ventilator-associated Bacterial Pneumonia, sponsored by Entasis Therapeutics. Completed at 92 sites in 17 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-02-01.

Sponsored by Entasis Therapeutics · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
207
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

02

Conditions studied

  • Acinetobacter Baumannii-calcoaceticus Complex
  • Hospital-acquired Bacterial Pneumonia
  • Ventilator-associated Bacterial Pneumonia
  • Bacteremia
  • Colistin Resistant ABC

Browse trials for

03

In context

Bacteremia

297 studies on the registry are indexed under Bacteremia; 51 are open to participants now.

This study's enrollment of 207 is above the median of 156 across 156 interventional studies indexed under Bacteremia.

Browse Bacteremia studies →

Lead sponsor

Entasis Therapeutics is the lead sponsor of 9 studies on the registry; none are open to participants now.

Of its 6 completed or terminated interventional studies of FDA-regulated products, 2 (33%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

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

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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 (ie, not 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 (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

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;
Terms in these criteria, in plain language(3)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Childbearing potential

Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).

Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.

Postmenopausal

Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
207 participants (actual)

Study arms

  • 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 · Drug: Durlobactam · Drug: Imipenem/Cilastatin 500 mg/500 mg

  • 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 · Drug: Imipenem/Cilastatin 500 mg/500 mg

  • 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 · Drug: Durlobactam · Drug: Imipenem/Cilastatin 500 mg/500 mg

Interventions

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

  • 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.

    Also known as: ETX2514

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

    Also known as: COLOMYCIN INJECTION 2 million IU/vial

  • DrugImipenem/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.

06

What researchers measure

Primary outcomes

  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.

    Time frame: 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.

    Time frame: 28 days

07

Results

Posted Feb 1, 2023

Participant flow

Participant flow — Overall Study
MilestonePart A - Group 1Part A - Group 2Part B - Group 3
Started928926
Completed696120
Not completed23286
Withdrew: Protocol violation100
Withdrew: Adverse event010
Withdrew: Withdrawal by subject231
Withdrew: Death15214
Withdrew: No growth of abc210
Withdrew: Physician decision111
Withdrew: Prohibited concomitant medication100
Withdrew: Transferred to other arm/group110

Outcome measures

PrimaryProportion 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.

Time frame:
28 Days
Reported as:
Count of participants · Participants
Proportion of Patients With All-Cause Mortality in CRABC m-MITT Population
ParticipantsPart A - Group 1Part A - Group 2
Proportion of Patients With All-Cause Mortality in CRABC m-MITT Population1220
Statistical analysis
  • Part A - Group 1 vs Part A - Group 2 · Mean difference (final values): -13.2 · 95% CI -30 to 3.5
PrimaryProportion 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.

Time frame:
28 days
Reported as:
Count of participants · Participants
Proportion of Patients With Nephrotoxicity
ParticipantsPart A - Group 1Part A - Group 2
Proportion of Patients With Nephrotoxicity1232
Statistical analysis
  • Part A - Group 1 vs Part A - Group 2 · Chi-squared · p = 0.0002 (p-value was obtained based on a Chi-Square test for treatment group differences.)

Adverse events

Collected over Adverse event monitoring starts from the time the patient consents to the study until up to 30 days after treatment.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Part A - Group 125/91 (27.5%)36/91 (39.6%)48/91 (52.7%)
Part A - Group 231/86 (36%)42/86 (48.8%)53/86 (61.6%)
Part B - Group 34/28 (14.3%)9/28 (32.1%)14/28 (50%)
Most frequent serious events
Showing 10 of 79
Most frequent serious events
EventPart A - Group 1Part A - Group 2Part B - Group 3
Septic shockInfections and infestations7/917/860/28
Multiple organ dysfunction syndromeGeneral disorders1/914/862/28
Cardiac arrestCardiac disorders2/914/861/28
PneumoniaInfections and infestations1/914/860/28
Shock haemorrhagicVascular disorders1/910/861/28
Ventricular tachycardiaCardiac disorders0/910/861/28
Respiratory failureRespiratory, thoracic and mediastinal disorders2/911/861/28
Pleural effusionRespiratory, thoracic and mediastinal disorders1/910/861/28
NeutropeniaBlood and lymphatic system disorders0/910/861/28
AscitesGastrointestinal disorders0/910/861/28
Most frequent other events
Showing 10 of 17
Most frequent other events
EventPart A - Group 1Part A - Group 2Part B - Group 3
DiarrhoeaGastrointestinal disorders15/919/862/28
AnaemiaBlood and lymphatic system disorders12/9111/864/28
Decubitus ulcerSkin and subcutaneous tissue disorders5/913/864/28
HypokalaemiaMetabolism and nutrition disorders13/919/860/28
Blood creatinine increasedInvestigations2/917/863/28
Enterococcus test positiveInvestigations0/910/863/28
Acute kidney injuryRenal and urinary disorders3/919/860/28
PyrexiaGeneral disorders9/918/861/28
Urinary tract infectionInfections and infestations7/918/861/28
Blood alkaline phosphatase increasedInvestigations0/911/862/28

Baseline characteristics

Two (2) participants were transferred from Part A to part B. These participants were analyzed at each arm until/ from the time point of transfer. The number of participants is reported according to the initial Arm/group in which individual participant was assigned.

Age, Categorical
Age, Categorical(Participants)Part A- Group 1Part A - Group 2Part B - Group 3Total
<=18 years0000
Between 18 and 65 years43371898
>=65 years49528109
Age, Continuous
Age, Continuous(years)Part A- Group 1Part A - Group 2Part B - Group 3Total
Mean63.4 ± 15.4266.9 ± 17.1356.2 ± 16.3359.8 ± 16.45
Sex: Female, Male
Sex: Female, Male(Participants)Part A- Group 1Part A - Group 2Part B - Group 3Total
Female2423552
Male686621155
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Part A- Group 1Part A - Group 2Part B - Group 3Total
American Indian or Alaska Native5207
Asian3344380
Native Hawaiian or Other Pacific Islander0000
Black or African American0101
White484123112
More than one race0000
Unknown or Not Reported6107
08

Study locations

92 sites
  • Entasis Research Site
    Chicago, Illinois 60611, United States
  • Entasis Research Site
    Shreveport, Louisiana 71101, United States
  • Entasis Research Site
    Cincinnati, Ohio 45219, United States
  • Entasis Research Site
    Memphis, Tennessee 38163, United States
  • Entasis Research Site
    Houston, Texas 77030, United States
  • Entasis Research Site
    Brest, Belarus
  • Entasis Research Site
    Gomel, Belarus
  • Entasis Research Site
    Grodno, Belarus
  • Entasis Research Site
    Minsk, Belarus
  • Entasis Research Site
    Belo Horizonte, Brazil
  • Entasis Research Site
    Campinas, Brazil
  • Entasis Research Site
    Porto Alegre, Brazil
  • Entasis Research Site
    Salvador, Brazil
  • Entasis Research Site
    Sao Jose do Rio Preto, Brazil
  • Entasis Research Site 1
    Beijing, China
  • Entasis Research Site 2
    Beijing, China
  • Entasis Research Site 3
    Beijing, China
  • Entasis Research Site
    Changsha, China
  • Entasis Research Site
    Chongqing, China
  • Entasis Research Site
    Guangzhou, China
  • Entasis Research Site
    Hebei, China
  • Entasis Research Site 1
    Hefei, China
  • Entasis Research Site 2
    Hefei, China
  • Entasis Research Site
    Hubei, China
  • Entasis Research Site
    Nanchang, China
  • Entasis Research Site
    Nanjing, China
  • Entasis Research Site
    Nanning, China
  • Entasis Research Site 1
    Shanghai, China
  • Entasis Research Site 2
    Shanghai, China
  • Entasis Research Site
    Shenzhen, China
  • Entasis Research Site
    Tianjin, China
  • Entasis Research Site
    Wuhan, China
  • Entasis Research Site 1
    Athens, Greece
  • Entasis Research Site 3
    Athens, Greece
  • Entasis Research Site
    Heraklion, Greece
  • Entasis Research Site
    Larisa, Greece
  • Entasis Research Site
    Larissa, Greece
  • Entasis Research Site
    Thessaloniki, Greece
  • Entasis Research Site 1
    Budapest, Hungary
  • Entasis Research Site 2
    Budapest, Hungary
  • Entasis Research Site
    Debrecen, Hungary
  • Entasis Research Site
    Ahmedabad, India
  • Entasis Research Site
    Belgaum, India
  • Entasis Research Site 2
    Gujrat, 382 428, India
  • Entasis Research Site 1
    Gujrat, 395002, India
  • Entasis Research Site
    Hyderabad, India
  • Entasis Research Site
    Kolkata, India
  • Entasis Research Site
    Pune, India
  • Entasis Research Site
    Holon, Israel
  • Entasis Research Site
    Tel Aviv, Israel
  • Entasis Research Site
    Tel Hashomer, Israel
  • Entasis Research Site
    Zerifin, Israel
  • Entasis Research Site
    Gyeonggi-do, Korea, Republic of
  • Entasis Research Site 1
    Seoul, Korea, Republic of
  • Entasis Research Site 2
    Seoul, Korea, Republic of
  • Entasis Research Site
    Kaunas, Lithuania
  • Entasis Research Site
    Klaipėda, Lithuania
  • Entasis Research Site
    Vilnius, Lithuania
  • Entasis Research Site 1
    Guadalajara, Mexico
  • Entasis Research Site 2
    Guadalajara, Mexico
  • Entasis Research Site
    Mexico DF, Mexico
  • Entasis Research Site
    Monterrey, Mexico
  • Entasis Research Site
    San Luis Potosi, Mexico
  • Entasis Research Site
    Bellavista, Peru
  • Entasis Research Site
    Cusco, Peru
  • Entasis Research Site
    Lima, Peru
  • Entasis Research Site
    San Isidro, Peru
  • Entasis Research Site
    San Martin de Porres, Peru
  • Entasis Research Site
    Ponce, Puerto Rico
  • Entasis Research Site
    Arkhangelsk, Russian Federation
  • Entasis Research Site
    Krasnodar, Russian Federation
  • Entasis Research Site 1
    Novosibirsk, Russian Federation
  • Entasis Research Site 2
    Novosibirsk, Russian Federation
  • Entasis Research Site 3
    Novosibirsk, Russian Federation
  • Entasis Research Site
    Smolensk, Russian Federation
  • Entasis Research Site 2
    St Petersburg, 192242, Russian Federation
  • Entasis Research Site 1
    Tomsk, Russian Federation
  • Entasis Research Site 2
    Tomsk, Russian Federation
  • Entasis Research Site
    Kaohsiung, Taiwan
  • Entasis Research Site
    Taichung, Taiwan
  • Entasis Research Site
    Taipei City, Taiwan
  • Entasis Research Site
    Taipei, Taiwan
  • Entasis Research Site
    Chiang Mai, Thailand
  • Entasis Research Site
    Khon Kaen, Thailand
  • Entasis Research Site
    Nakhon Ratchasima, Thailand
  • Entasis Research Site
    Nonthaburi, Thailand
  • Entasis Research Site 1
    Ankara, Turkey
  • Entasis Research Site 2
    Ankara, Turkey
  • Entasis Research Site
    Eskişehir, Turkey
  • Entasis Research Site
    Kocaeli, Turkey
  • Entasis Research Site
    Küçükçekmece, Turkey
  • Entasis Research Site
    Trabzon, Turkey
09

References and documents

Study documents

PDFs hosted by the registry, ClinicalTrials.gov.

10

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Ran from Sep 2019 to primary completion in Jul 2021, 22 months.

Results were first posted in Feb 2023, 1 year 6 months after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered
Mar 27, 2019
First posted
Mar 28, 2019
StartActual
Sep 5, 2019
Primary completionActual
Jul 26, 2021
CompletionActual
Jul 26, 2021
Results first posted
Feb 1, 2023
Last update
Feb 1, 2023
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Feb 1, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03894046
Lead sponsor
Entasis Therapeutics
Responsible party
Sponsor
First posted
Mar 28, 2019
Start date
Sep 5, 2019
Primary completion
Jul 26, 2021
Completion
Jul 26, 2021
Results posted
Feb 1, 2023
Last update
Feb 1, 2023

Oversight

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

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Studies of the drug tested here: Durlobactam

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