Study of 2 Medicines (Aztreonam and Avibactam) Compared to Best Available Therapy for Serious Gram-negative Infections
A PHASE 2A MULTICENTER, OBSERVER-BLINDED, RANDOMIZED 2 ARM STUDY TO INVESTIGATE PHARMACOKINETICS, SAFETY, TOLERABILITY AND EFFICACY OF INTRAVENOUS AZTREONAM-AVIBACTAM ± METRONIDAZOLE COMPARED TO BEST AVAILABLE THERAPY (BAT) IN PEDIATRIC PARTICIPANTS 9 MONTHS TO LESS THAN 18 YEARS OF AGE WITH SERIOUS GRAM-NEGATIVE BACTERIAL INFECTIONS INCLUDING COMPLICATED INTRA-ABDOMINAL INFECTION
Pfizer
48 participants
Apr 18, 2023
INTERVENTIONAL
Summary
The purpose of this study is to evaluate how Aztreonam (ATM) and Avibactam (AVI) are processed in pediatric participants. This study also aims to understand participant safety and effects in pediatric participants. 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.
Eligibility
Inclusion Criteria3
- Participants ≥9 months to <18 years of age at Screening; Female (post-menarchal) participants must have a negative serum/urine pregnancy test (β hCG sensitivity ≥25 mIU/mL).
- Suspected/confirmed cIAI, cUTI, HAP/VAP, or BSI with gram-negative pathogens.
- Require hospitalization and IV antibiotic treatment.
Exclusion Criteria11
- Participants with any of the following characteristics/conditions will be excluded:
- 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.
- Gram-negative species not expected to respond to ATM AVI ≤14 days.
- 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):
- 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.
- 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.
- 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).
- CrCL ≤15 mL/min/1.73 m2 (eCrCl or eGFR calculation based on age).
- 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).
- 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.
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Interventions
A drug specifically designed to treat resistant gam-negative bacterial infections
BAT will be selected by the investigator and administered iv as appropriate for the selected drug(s)
Locations(24)
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NCT05639647