Study of 2 Medicines (Aztreonam and Avibactam) Compared to Best Available Therapy for Serious Gram-negative Infections
NCT ID: NCT05639647
Last Updated: 2026-02-03
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
RECRUITING
PHASE2
48 participants
INTERVENTIONAL
2023-04-18
2026-08-17
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
The study is seeking participants who are:
* 9 months to less than 18 years of age
* Hospitalized
* Suspected/known to have a gram-negative infection
* Receiving intravenous (iv, given directly into a vein) antibiotics
* Being treated for complicated infections of various body parts that includes the abdomen, urinary tract, blood stream, and lungs.
* Participants will receive either ATM-AVI or best available therapy (BAT).
* Both therapies will be given through a vein.
* Participants with complicated abdominal infections will also receive iv Metronidazole (MTZ). Patients with cIAI and Cockayne Syndrome are excluded due to a risk of severe hepatotoxicity with the use of MTZ. - Participants on ATM-AVI treatment who have anaerobic infections will also receive iv MTZ at the study doctor's discretion.
* The iv dose of ATM-AVI will be based on the participant's weight and kidney function.
* The study doctor will determine the iv dose of BAT.
* During the first 2 study days, participants on ATM-AVI therapy will have 5 blood draws in small quantities.
* Starting on day 4, the study doctor will decide if participants may be switched to oral therapy.
* Participants will receive a maximum of 14 days of ATM-AVI treatment.
* After discharge from the hospital, 1 study visit may be required.
* Depending on the participant's response, the study duration will be from 33 to 50 days.
* The investigator will contact participants by phone 28 to 35 days after the last study treatment to check participants health status.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
A Study to Determine the Efficacy, Safety and Tolerability of Aztreonam-Avibactam (ATM-AVI) ± Metronidazole (MTZ) Versus Meropenem (MER) ± Colistin (COL) for the Treatment of Serious Infections Due to Gram Negative Bacteria.
NCT03329092
Efficacy, Safety, and Tolerability of ATM-AVI in the Treatment of Serious Infection Due to MBL-producing Gram-negative Bacteria
NCT03580044
A Study to Learn About the Study Medicine Aztreonam-Avibactam (ATM-AVI) in Infants and Newborns Admitted in Hospitals With Bacterial Infection (CHERISH)
NCT06462235
To Investigate the Safety and Tolerability of Aztreonam-Avibactam (ATM-AVI)
NCT01689207
Safety and Tolerability of Ceftazidime-Avibactam for Pediatric Patients With Suspected or Confirmed Infections
NCT01893346
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
* Although cultures are required, isolation of the causative pathogen is not a criteria for enrollment. - cUTI participants requiring systemic prophylactic antibiotics for any reason at screening are allowed to enter the study provided they discontinue this medication prior to first study drug dose.
* If the participant satisfies the inclusion and exclusion requirements, the participant will be randomly enrolled in a ratio of 3 iv ATM-AVI for each iv BAT.
* A total of 48 participants at approximately 33 sites will be randomized using interactive response technology (IRT).
* The study will be multicenter, international and open label with a single blinded observer assigned by each investigational site.
* There will be 4 cohorts with ages 12 to less than 18 years (Cohort 1), 6 to less than 12 years (Cohort 2), 2 to less than 6 years (Cohort 3) and 9 months to less than 2 years (Cohort 4).
* Each cohort will have 12 participants for a total of 48 participants.
* Cohorts 1 and 2 will be enrolled simultaneously. - - Cohort 3 will begin enrollment after the first 4 participants complete Cohort 2 and PK data and safety have been reviewed by the sponsor and an external data monitoring committee (DMC). Then ATM-AVI dose may be adjusted as needed.
* Cohort 4 will begin enrollment after the first 4 participants completed Cohort 3 and the PK data have been reviewed by the sponsor and the DMC. Then the ATM-AVI dose may be adjusted as needed.
* After 4 participants complete Cohort 4 the PK data will be review by the sponsor and DMC and then the ATM-AVI dose may be adjusted as needed.
* Enrollment will not be paused during the PK data reviews of the first 4 ATM-AVI participants in a cohort. If the ATM-AVI dose requires adjustment, the cohort 4 number will be increased to 20 with 15 receiving ATM-AVI and 5 BAT.
* All participants in the ATM-AVI group will receive an initial ATM-AVI loading dose and then maintenance doses every 6 or 8 hours depending on the participant's weight and kidney function.
* ATM-AVI will be infused over 3 hours.
* Those with cIAI will receive metronidazole (MTZ). Patients with cIAI and Cockayne Syndrome are excluded due to a risk of severe hepatotoxicity with the use of MTZ. - At the investigator's discretion MTZ will be administered to those with BSI, cUTI or HAP/VAP and an associated anaerobic infection.
* MTZ will be administered iv over 20 to 30 minutes starting.
* Optional gram-positive coverage with vancomycin, teicoplanin and linezolid is permitted. Daptomycin is only permitted for cIAI and BSI participants.
* Coverage with iv aminoglycoside is permitted for Pseudomonas aeruginosa.
* Concerning concomitant medications, participants with cUTI may not take prophylactic therapy during study drug treatment.
* Systemic antibiotics are not permitted unless the study drug failed, or it is for a remote site infection essential for participant's safety.
* Systemic iv antivirals are permitted.
* Systemic antifungals should be avoided unless indicated.
* Meropenem/carbapenem-type antibiotics cannot be given concomitantly with ATM-AVI.
* Probenecid and inhaled antibiotics are to be avoided from informed consent until the end of iv treatment (EOIV).
* Antibiotic peritoneal lavage is not permitted. Non-antibiotic lavage is permitted.
* The primary endpoints are pharmacokinetics (PK) and safety.
* Five PK micro-blood samples of at least 0.1 mL will be drawn. The initial 2 PK micro blood samples will be drawn at 2 hours and 5 hours after the first infusion. The next 3 PK micro-blood samples will be drawn at 15 minutes before, 5 hours and 5 3/4 hours after the 5th infusion or a later infusion.
* ATM and AVI clearance (CL), maximum (Cmax) and minimum (Cmin) venous blood concentration, area under the curve (AUC) and half-life (t1/2) will be analyzed.
* A blinded observer (BO), assigned by each investigational site, will clinically assess the participants every day.
* The BO will evaluate causality of all adverse events (AEs) and serious adverse events (SAEs) while the participant is in the hospital, within 24 hours of the end of iv study drug (EOIV), and within 48 hours of end of treatment for those switched to oral therapy.
* For the secondary endpoint of efficacy, the BO will clinically assess the test of cure (TOC) within 7 to 14 days of the last antibiotic treatment. Potential for liver function abnormalities and acute kidney injury will be specifically monitored in addition to standard of care assessments.
* Cure is defined as signs and symptoms improved with no further antimicrobial treatment required except for adjunctive gram-positive therapy or for Pseudomonas aeruginosa.
* In addition, for cIAI participants, no unplanned drainage or surgical intervention is necessary since the initial surgical procedure. Only for those switched to oral therapy before 14 days, improvement is afebrile with absence of new signs or symptoms and improvement of 1 or more symptoms or signs with no worsening of signs or symptoms.
* Failure is defined as death, requirement of antibiotics for the index infection, or discontinuation due to an AE(s). cIAI participants have additional failure criteria of requiring surgical intervention and/or have an infected post-surgical wound(s).
* Participant may choose to permanently discontinue and are free to discontinue treatment without further treatment prejudice. Possible reasons for permanent discontinuation are:
* Condition under investigation resolved prior to minimum treatment period
* AE or any other condition posing a risk to a participant or jeopardizing safety
* Investigator, national coordinators, medical monitor, and/or Sponsor decided it is in the best interest of the participant's safety
* Positive pregnancy test during the treatment period
* Absence of explanation for liver injury and/or increase in liver function tests or acute kidney toxicity
* Discontinuation of intervention does not represent withdrawal from the study and participants should remain in the study until the end of the study (EOS).
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
SINGLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
ATM-AVI
ATM-AVI administered iv every 6 or 8 hours and dosed according to participant's weight and kidney function for up to 14 days depending on response. At the investigator's discretion, the participant may be switched to oral therapy after 3 days of iv ATM-AVI therapy
ATM-AVI
A drug specifically designed to treat resistant gam-negative bacterial infections
Best available therapy (BAT)
BAT will be selected by the investigator and administered iv. At the investigator's discretion, the participant may be switched to oral therapy after 3 days of iv BAT
BAT
BAT will be selected by the investigator and administered iv as appropriate for the selected drug(s)
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
ATM-AVI
A drug specifically designed to treat resistant gam-negative bacterial infections
BAT
BAT will be selected by the investigator and administered iv as appropriate for the selected drug(s)
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
2. Suspected/confirmed cIAI, cUTI, HAP/VAP, or BSI with gram-negative pathogens.
3. Require hospitalization and IV antibiotic treatment.
Exclusion Criteria
1. Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
2. Gram-negative species not expected to respond to ATM AVI ≤14 days.
3. Pregnant or breastfeeding; fertile male/female unwilling/unable to use effective contraception for at ≥7 days (males) or ≥28 days (females) after last ATM-AVI infusion.
(HAP/VAP only):
4. Microbiologically known or high likelihood of monomicrobial infection with a gram-positive organism, lung abscess, pleural empyema, or post-obstructive pneumonia, lung or heart transplant.
5. Received \>24 hours of systemic antibiotics during the 48 hours before randomization unless participant has documented treatment failure after at least 48 hours of antibiotic therapy.
6. Current use of any prohibited concomitant medication(s) or unwilling/unable (Cockayne Syndrome patients with cIAI are excluded) to use MTZ or having received previous investigational drug(s) or vaccine ≤30 days or 5 half-lives before randomization (whichever is longer).
7. CrCL ≤15 mL/min/1.73 m2 (eCrCl or eGFR calculation based on age).
8. Non-infectious related screening ALT or AST \>3 x ULN, ALP \>3 x ULN and/or TBili \>2 x ULN (\> 3 x ULN for Gilbert's syndrome).
9. Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members.
9 Months
17 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Pfizer
INDUSTRY
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Pfizer CT.gov Call Center
Role: STUDY_DIRECTOR
Pfizer
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Rady Children's Hospital
San Diego, California, United States
Weill Cornell Medicine-New York Presbyterian Hospital
New York, New York, United States
Icahn School of Medicine at Mount Sinai
New York, New York, United States
Mount Sinai Kravis Children´s Hospital
New York, New York, United States
The Mount Sinai Hospital
New York, New York, United States
Le Bonheur Children's Hospital
Memphis, Tennessee, United States
Beijing Children's Hospital, Capital Medical University
Beijing, Beijing Municipality, China
Guangzhou Women and Children's Medical Center
Guangzhou, Guangdong, China
Shanghai Children's Medical Center
Shanghai, , China
University General Hospital of Heraklion
Heraklion, Irakleío, Greece
Ippokrateio General Hospital of Thessaloniki
Thessaloniki, Kentrikí Makedonía, Greece
Semmelweis Egyetem
Budapest, , Hungary
Semmelweis Egyetem
Budapest, , Hungary
Nirmal Hospital Pvt Ltd.
Surat, Gujarat, India
RajaRajeswari Medical College and Hospital
Bangalore, Karnataka, India
Sahaydri Super Speciality Hospital, Nagar road
Pune, Maharashtra, India
Medanta Hospital Lucknow
Lucknow, Uttar Pradesh, India
Institute of Child Health
Kolkata, West Bengal, India
Hospital Germans Trias i Pujol
Badalona, Barcelona [barcelona], Spain
Hospital Sant Joan de Déu
Esplugues de Llobregat, Barcelona [barcelona], Spain
Hospital Universitario HM Monteprincipe
Boadilla del Monte, Madrid, Spain
Hospital Universitario La Paz
Madrid, Madrid, Comunidad de, Spain
Hospital Universitari Vall d'Hebron
Barcelona, , Spain
Hospital Universitario 12 de Octubre
Madrid, , Spain
Hsinchu Municipal Mackay Children's Hospital
Hsinchu, Hsinchu, Taiwan
National Taiwan University Hospital
Taipei, , Taiwan
Chang Gung Medical Foundation-Linkou Branch
Taoyuan District, , Taiwan
Cukurova Universty
Sarçam, Adana, Turkey (Türkiye)
Istanbul Universitesi Istanbul Tıp Fakultesi Hastanesi
Istanbul, İ̇stanbul, Turkey (Türkiye)
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Related Links
Access external resources that provide additional context or updates about the study.
To obtain contact information for a study center near you, click here.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
2022-501575-12-00
Identifier Type: REGISTRY
Identifier Source: secondary_id
C3601008
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.