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

Bacteremia Clinical Trial

— ATTACK  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03894046
• Other study ID #: CS2514-2017-0004
• Status: Completed
• Phase: Phase 3
• Start date: September 5, 2019
• Est. completion date: July 26, 2021

Study information

• Verified date: January 2023
• Source: Entasis Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 207
• Est. completion date: July 26, 2021
• Est. primary completion date: July 26, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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;

Related Conditions & MeSH terms

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

Intervention

Drug:
• Sulbactam
1.0 g sulbactam IV infused over 3 hours every 6 hours (q6h).
• 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.
• Colistin
Treatment for 7 days up to 14 days if clinically indicated.
• 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.

Locations

Country	Name	City	State
Belarus	Entasis Research Site	Brest
Belarus	Entasis Research Site	Gomel
Belarus	Entasis Research Site	Grodno
Belarus	Entasis Research Site	Minsk
Brazil	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
China	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
Greece	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
Hungary	Entasis Research Site 1	Budapest
Hungary	Entasis Research Site 2	Budapest
Hungary	Entasis Research Site	Debrecen
India	Entasis Research Site	Ahmedabad
India	Entasis Research Site	Belgaum
India	Entasis Research Site 1	Gujrat
India	Entasis Research Site 2	Gujrat
India	Entasis Research Site	Hyderabad
India	Entasis Research Site	Kolkata
India	Entasis Research Site	Pune
Israel	Entasis Research Site	Holon
Israel	Entasis Research Site	Tel Aviv
Israel	Entasis Research Site	Tel Hashomer
Israel	Entasis Research Site	Zerifin
Korea, Republic of	Entasis Research Site	Gyeonggi-do
Korea, Republic of	Entasis Research Site 1	Seoul
Korea, Republic of	Entasis Research Site 2	Seoul
Lithuania	Entasis Research Site	Kaunas
Lithuania	Entasis Research Site	Klaipeda
Lithuania	Entasis Research Site	Vilnius
Mexico	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
Peru	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
Puerto Rico	Entasis Research Site	Ponce
Russian Federation	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
Russian Federation	Entasis Research Site 1	Tomsk
Russian Federation	Entasis Research Site 2	Tomsk
Taiwan	Entasis Research Site	Kaohsiung
Taiwan	Entasis Research Site	Taichung
Taiwan	Entasis Research Site	Taipei
Taiwan	Entasis Research Site	Taipei City
Thailand	Entasis Research Site	Chiang Mai
Thailand	Entasis Research Site	Khon Kaen
Thailand	Entasis Research Site	Nakhon Ratchasima
Thailand	Entasis Research Site	Nonthaburi
Turkey	Entasis Research Site 1	Ankara
Turkey	Entasis Research Site 2	Ankara
Turkey	Entasis Research Site	Eskisehir
Turkey	Entasis Research Site	Kocaeli
Turkey	Entasis Research Site	Küçükçekmece
Turkey	Entasis Research Site	Trabzon
United States	Entasis Research Site	Chicago	Illinois
United States	Entasis Research Site	Cincinnati	Ohio
United States	Entasis Research Site	Houston	Texas
United States	Entasis Research Site	Memphis	Tennessee
United States	Entasis Research Site	Shreveport	Louisiana

Sponsors (1)

Lead Sponsor	Collaborator
Entasis Therapeutics

Countries where clinical trial is conducted

United States,  Belarus,  Brazil,  China,  Greece,  Hungary,  India,  Israel,  Korea, Republic of,  Lithuania,  Mexico,  Peru,  Puerto Rico,  Russian Federation,  Taiwan,  Thailand,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	28 Days
Primary	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.	28 days