Clinical trial NCT03894046: Study to Evaluate the Efficacy and Safety of Intravenous Sulbactam-ETX2514 in the Treatment of Patients With Infections Caused by Acinetobacter Baumannii-calcoaceticus Complex
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acinetobacter Baumannii-calcoaceticus Complex
Hospital-acquired Bacterial Pneumonia
Ventilator-associated Bacterial Pneumonia
Bacteremia
Colistin Resistant ABC
Lead sponsor: Entasis Therapeutics
Sponsor class: INDUSTRY
First posted: 2019-03-28
Enrollment: 207
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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;

Primary outcomes:
measure: Proportion of Patients With All-Cause Mortality in CRABC m-MITT Population
timeFrame: 28 Days
measure: Proportion of Patients With Nephrotoxicity
timeFrame: 28 days
Secondary outcomes:
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Entasis Research Site
state: Illinois
city: Shreveport
country: United States
facility: Entasis Research Site
state: Louisiana
city: Cincinnati
country: United States
facility: Entasis Research Site
state: Ohio
city: Memphis
country: United States
facility: Entasis Research Site
state: Tennessee
city: Houston
country: United States
facility: Entasis Research Site
state: Texas
city: Brest
country: Belarus
facility: Entasis Research Site
city: Gomel
country: Belarus
facility: Entasis Research Site
city: Grodno
country: Belarus
facility: Entasis Research Site
city: Minsk
country: Belarus
facility: Entasis Research Site
city: Belo Horizonte
country: Brazil
facility: Entasis Research Site
city: Campinas
country: Brazil
facility: Entasis Research Site
city: Porto Alegre
country: Brazil
facility: Entasis Research Site
city: Salvador
country: Brazil
facility: Entasis Research Site
city: Sao Jose do Rio Preto
country: Brazil
facility: Entasis Research Site
city: Beijing
country: China
facility: Entasis Research Site 1
city: Beijing
country: China
facility: Entasis Research Site 2
city: Beijing
country: China
facility: Entasis Research Site 3
city: Changsha
country: China
facility: Entasis Research Site
city: Chongqing
country: China
facility: Entasis Research Site
city: Guangzhou
country: China
facility: Entasis Research Site
city: Hebei
country: China
facility: Entasis Research Site
city: Hefei
country: China
facility: Entasis Research Site 1
city: Hefei
country: China
facility: Entasis Research Site 2
city: Hubei
country: China
facility: Entasis Research Site
city: Nanchang
country: China
facility: Entasis Research Site
city: Nanjing
country: China
facility: Entasis Research Site
city: Nanning
country: China
facility: Entasis Research Site
city: Shanghai
country: China
facility: Entasis Research Site 1
city: Shanghai
country: China
facility: Entasis Research Site 2
city: Shenzhen
country: China
facility: Entasis Research Site
city: Tianjin
country: China
facility: Entasis Research Site
city: Wuhan
country: China
facility: Entasis Research Site
city: Athens
country: Greece
facility: Entasis Research Site 1
city: Athens
country: Greece
facility: Entasis Research Site 3
city: Heraklion
country: Greece
facility: Entasis Research Site
city: Larisa
country: Greece
facility: Entasis Research Site
city: Larissa
country: Greece
facility: Entasis Research Site
city: Thessaloniki
country: Greece
facility: Entasis Research Site
city: Budapest
country: Hungary
facility: Entasis Research Site 1
city: Budapest
country: Hungary
facility: Entasis Research Site 2
city: Debrecen
country: Hungary
facility: Entasis Research Site
city: Ahmedabad
country: India
facility: Entasis Research Site
city: Belgaum
country: India
facility: Entasis Research Site
city: Gujrat
country: India
facility: Entasis Research Site 2
city: Gujrat
country: India
facility: Entasis Research Site 1
city: Hyderabad
country: India
facility: Entasis Research Site
city: Kolkata
country: India
facility: Entasis Research Site
city: Pune
country: India
facility: Entasis Research Site
city: Holon
country: Israel
facility: Entasis Research Site
city: Tel Aviv
country: Israel
facility: Entasis Research Site
city: Tel Hashomer
country: Israel
facility: Entasis Research Site
city: Zerifin
country: Israel
facility: Entasis Research Site
city: Gyeonggi-do
country: Korea, Republic of
facility: Entasis Research Site
city: Seoul
country: Korea, Republic of
facility: Entasis Research Site 1
city: Seoul
country: Korea, Republic of
facility: Entasis Research Site 2
city: Kaunas
country: Lithuania
facility: Entasis Research Site
city: Klaipėda
country: Lithuania
facility: Entasis Research Site
city: Vilnius
country: Lithuania
facility: Entasis Research Site
city: Guadalajara
country: Mexico
facility: Entasis Research Site 1
city: Guadalajara
country: Mexico
facility: Entasis Research Site 2
city: Mexico DF
country: Mexico
facility: Entasis Research Site
city: Monterrey
country: Mexico
facility: Entasis Research Site
city: San Luis Potosi
country: Mexico
facility: Entasis Research Site
city: Bellavista
country: Peru
facility: Entasis Research Site
city: Cusco
country: Peru
facility: Entasis Research Site
city: Lima
country: Peru
facility: Entasis Research Site
city: San Isidro
country: Peru
facility: Entasis Research Site
city: San Martin de Porres
country: Peru
facility: Entasis Research Site
city: Ponce
country: Puerto Rico
facility: Entasis Research Site
city: Arkhangelsk
country: Russian Federation
facility: Entasis Research Site
city: Krasnodar
country: Russian Federation
facility: Entasis Research Site
city: Novosibirsk
country: Russian Federation
facility: Entasis Research Site 1
city: Novosibirsk
country: Russian Federation
facility: Entasis Research Site 2
city: Novosibirsk
country: Russian Federation
facility: Entasis Research Site 3
city: Smolensk
country: Russian Federation
facility: Entasis Research Site
city: St Petersburg
country: Russian Federation
facility: Entasis Research Site 2
city: Tomsk
country: Russian Federation
facility: Entasis Research Site 1
city: Tomsk
country: Russian Federation
facility: Entasis Research Site 2
city: Kaohsiung
country: Taiwan
facility: Entasis Research Site
city: Taichung
country: Taiwan
facility: Entasis Research Site
city: Taipei City
country: Taiwan
facility: Entasis Research Site
city: Taipei
country: Taiwan
facility: Entasis Research Site
city: Chiang Mai
country: Thailand
facility: Entasis Research Site
city: Khon Kaen
country: Thailand
facility: Entasis Research Site
city: Nakhon Ratchasima
country: Thailand
facility: Entasis Research Site
city: Nonthaburi
country: Thailand
facility: Entasis Research Site
city: Ankara
country: Turkey
facility: Entasis Research Site 1
city: Ankara
country: Turkey
facility: Entasis Research Site 2
city: Eskişehir
country: Turkey
facility: Entasis Research Site
city: Kocaeli
country: Turkey
facility: Entasis Research Site
city: Küçükçekmece
country: Turkey
facility: Entasis Research Site
city: Trabzon
country: Turkey
facility: Entasis Research Site
Study officials:
References: