ATM-AVI for Bacterial Infections

Recruiting in Palo Alto (17 mi)

+38 other locations

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Pfizer

Must be taking: Intravenous antibiotics

Must not be taking: Prohibited concomitant medications

Disqualifiers: Pregnancy, Suicidal ideation, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it mentions that current use of any prohibited medications is not allowed. It's best to discuss your current medications with the study doctor to see if they are allowed.

What data supports the effectiveness of the drug ATM-AVI for bacterial infections?

Research shows that the combination of ceftazidime-avibactam (a part of ATM-AVI) is effective against various drug-resistant bacteria, including those causing complicated abdominal and urinary tract infections. Additionally, aztreonam/avibactam, another component, shows promise in treating highly resistant bacterial infections. ^{1 2 3 4 5}

Is ATM-AVI generally safe for humans?

Ceftazidime-avibactam, a component of ATM-AVI, is generally well tolerated in humans, with a safety profile similar to other injectable antibiotics. It has been used safely in treating serious infections, suggesting that ATM-AVI may also be safe, but specific safety data for ATM-AVI is still pending further clinical trials. ^{1 2 4 6 7}

What makes the drug ATM-AVI unique for treating bacterial infections?

ATM-AVI is unique because it combines aztreonam with avibactam to target bacteria that produce metallo-β-lactamases, enzymes that make them resistant to many antibiotics. This combination is particularly effective against difficult-to-treat infections caused by certain resistant bacteria, like Klebsiella pneumoniae, which are not easily managed by standard antibiotics. ^{8 9 10 11 12}

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

This trial is for hospitalized children aged 9 months to less than 18 years with suspected or confirmed serious gram-negative infections, requiring IV antibiotics. It's not for those unlikely to respond to the study drugs within 14 days, pregnant/breastfeeding individuals without effective contraception, or those with certain medical conditions.

Inclusion Criteria

I have an infection suspected to be caused by gram-negative bacteria.

I am between 9 months and 18 years old.

I am a woman and my pregnancy test was negative.

Exclusion Criteria

My kidney function is very low.

I am not currently taking any prohibited medications and have not participated in another drug study within the last 30 days or 5 half-lives.

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 make the participant inappropriate for the study

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 days

Treatment

Participants receive intravenous ATM-AVI or BAT for up to 14 days, with potential switch to oral therapy after 3 days

14 days

Daily in-hospital visits

Follow-up

Participants are monitored for safety and effectiveness after treatment, including a phone contact 28 to 35 days after the last study treatment

33 to 50 days

1 in-person visit after discharge, phone contact

Test of Cure (TOC)

Clinical assessment of cure within 7 to 14 days after the last antibiotic treatment

7 to 14 days

Treatment Details

Interventions

• Avibactam (Beta-lactamase inhibitor)
• Aztreonam (Antibiotic)

Trial Overview The trial compares Aztreonam and Avibactam (ATM-AVI) combination against the best available therapy (BAT) in treating complicated infections like abdominal, urinary tract, bloodstream, and lung infections. ATM-AVI dosage depends on weight and kidney function; treatment lasts up to 14 days with possible switch to oral therapy.

Participant Groups

Group I: ATM-AVI Experimental Treatment 1 Intervention

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

Group II: Best available therapy (BAT) Active Control 1 Intervention

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Weill Cornell Medicine-New York Presbyterian Hospital New York, NY

Le Bonheur Children's Hospital Memphis, TN

Rady Children's Hospital San Diego, CA

Mount Sinai Kravis Children´s Hospital New York, NY

More Trial Locations

Who Is Running the Clinical Trial?

Pfizer

Lead Sponsor

Trials

4712

Patients Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Findings from Research

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phenotypic synergy testing of ceftazidime-avibactam with aztreonam in a university hospital having high number of metallobetalactamase producing bacteria. Sahu, C., Pal, S., Patel, SS., et al.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing the in vitro impact of ceftazidime on aztreonam/avibactam susceptibility testing for highly resistant MBL-producing Enterobacterales. Bhatnagar, A., Ransom, EM., Machado, MJ., et al.[2021]

Ceftazidime/avibactam is an effective new antibiotic combination that restores the antibacterial activity of ceftazidime against drug-resistant bacteria, particularly those producing carbapenemase, such as KPC-producing Klebsiella pneumoniae.

The medication has shown promise in treating various infections, including lung, abdominal, bloodstream, and urinary tract infections, while also addressing clinical safety and indications for its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Several key points that need to be concerned in the clinical application of ceftazidime/avibactam]. Tang, B., Cui, N.[2021]

Ceftazidime-avibactam (Avycaz) is effective in treating complicated infections, particularly those caused by multidrug-resistant bacteria.

The combination of ceftazidime and avibactam enhances the efficacy of treatment by inhibiting bacterial resistance mechanisms, making it a valuable option for difficult-to-treat infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ceftazidime-Avibactam (Avycaz): For the Treatment of Complicated Intra-Abdominal and Urinary Tract Infections. Mosley, JF., Smith, LL., Parke, CK., et al.[2020]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of ceftazidime-avibactam for the treatment of infections due to Pseudomonas aeruginosa. Corbella, L., Boán, J., San-Juan, R., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aztreonam-Avibactam Susceptibility Testing Program for Metallo-Beta-Lactamase-Producing Enterobacterales in the Antibiotic Resistance Laboratory Network, March 2019 to December 2020. Bhatnagar, A., Boyd, S., Sabour, S., et al.[2022]

Ceftazidime-avibactam is effective against a wide range of drug-resistant Gram-negative bacteria, including those producing extended-spectrum β-lactamases, making it a valuable treatment for complicated infections like urinary tract infections and hospital-acquired pneumonia.

In clinical trials, ceftazidime-avibactam demonstrated high response rates and was generally well tolerated, showing a safety profile similar to that of ceftazidime alone, which supports its use as a new treatment option for serious infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ceftazidime-Avibactam: A Review in the Treatment of Serious Gram-Negative Bacterial Infections. Shirley, M.[2019]

In a study of 102 patients with bloodstream infections caused by metallo-β-lactamase-producing Enterobacterales, the combination of ceftazidime-avibactam (CAZ-AVI) and aztreonam (ATM) significantly reduced the 30-day mortality rate to 19.2%, compared to 44% in those treated with other active antibiotics.

The CAZ-AVI + ATM treatment also led to lower clinical failure rates at day 14 and shorter hospital stays, indicating its potential as a more effective therapy for these serious infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Ceftazidime-avibactam Plus Aztreonam in Patients With Bloodstream Infections Caused by Metallo-β-lactamase-Producing Enterobacterales. Falcone, M., Daikos, GL., Tiseo, G., et al.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A simple disk pre-diffusion test to predict in vitro aztreonam/avibactam activity against NDM-producing Klebsiella pneumoniae complex. Lima, KO., de Lima, AV., Rocha, DADC., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A practical laboratory method to determine ceftazidime-avibactam-aztreonam synergy in patients with New Delhi metallo-beta-lactamase (NDM)-producing Enterobacterales infection. Rawson, TM., Brzeska-Trafny, I., Maxfield, R., et al.[2023]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro activity of aztreonam/avibactam against a global collection of Klebsiella pneumoniae collected from defined culture sources in 2016 and 2017. Esposito, S., Stone, GG., Papaparaskevas, J.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suboptimal drug exposure leads to selection of different subpopulations of ceftazidime-avibactam-resistant Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae in a critically ill patient. Gaibani, P., Gatti, M., Rinaldi, M., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Phenotypic synergy testing of ceftazidime-avibactam with aztreonam in a university hospital having high number of metallobetalactamase producing bacteria. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Assessing the in vitro impact of ceftazidime on aztreonam/avibactam susceptibility testing for highly resistant MBL-producing Enterobacterales. [2021]

3. China pubmed.ncbi.nlm.nih.gov

[Several key points that need to be concerned in the clinical application of ceftazidime/avibactam]. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Ceftazidime-Avibactam (Avycaz): For the Treatment of Complicated Intra-Abdominal and Urinary Tract Infections. [2020]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Effectiveness of ceftazidime-avibactam for the treatment of infections due to Pseudomonas aeruginosa. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Aztreonam-Avibactam Susceptibility Testing Program for Metallo-Beta-Lactamase-Producing Enterobacterales in the Antibiotic Resistance Laboratory Network, March 2019 to December 2020. [2022]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Ceftazidime-Avibactam: A Review in the Treatment of Serious Gram-Negative Bacterial Infections. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Efficacy of Ceftazidime-avibactam Plus Aztreonam in Patients With Bloodstream Infections Caused by Metallo-β-lactamase-Producing Enterobacterales. [2021]

9. Netherlands pubmed.ncbi.nlm.nih.gov

A simple disk pre-diffusion test to predict in vitro aztreonam/avibactam activity against NDM-producing Klebsiella pneumoniae complex. [2022]

10. Netherlands pubmed.ncbi.nlm.nih.gov

A practical laboratory method to determine ceftazidime-avibactam-aztreonam synergy in patients with New Delhi metallo-beta-lactamase (NDM)-producing Enterobacterales infection. [2023]

11. Netherlands pubmed.ncbi.nlm.nih.gov

In vitro activity of aztreonam/avibactam against a global collection of Klebsiella pneumoniae collected from defined culture sources in 2016 and 2017. [2021]

12. Canada pubmed.ncbi.nlm.nih.gov

Suboptimal drug exposure leads to selection of different subpopulations of ceftazidime-avibactam-resistant Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae in a critically ill patient. [2022]