Imipenem-Relebactam for Obesity in ICU Patients

Overseen By Eric Wenzler, PharmD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Illinois at Chicago

Must not be taking: Antimicrobials, Valproic acid

Disqualifiers: Seizures, High creatinine, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how the drugs imipenem (an antibiotic) and relebactam behave in the bodies of obese ICU patients. Researchers intend to track how these drugs are processed and ensure their safety for this specific group. The trial seeks ICU patients who are not currently fighting an infection and have a body mass index (BMI) of 40 or more or weigh over 120 kg. As a Phase 4 trial, this research focuses on how these FDA-approved and effective treatments can benefit more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking certain medications like anti-epileptic agents or valproic acid. It's best to discuss your current medications with the study team.

What is the safety track record for imipenem/cilastatin and relebactam?

Research has shown that imipenem-cilastatin and relebactam are generally well-tolerated. Trials with these medications reported side effects that were usually mild and manageable. Common side effects included nausea and diarrhea, while serious side effects were rare.

The FDA has approved imipenem-cilastatin-relebactam for treating certain bacterial infections, indicating a good safety record. This approval means it has been tested and used in people before, adding to the evidence of its safety.

Although obesity can affect how drugs work in the body, studies in ICU patients have shown that adjusting the dose can help manage this, ensuring the treatment remains safe and effective.

Prospective trial participants should discuss potential risks and benefits with a doctor. A doctor can provide personalized advice based on individual health needs. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the combination of Imipenem/Cilastatin and Relebactam for obesity in ICU patients because it offers a new approach to managing infections in this challenging population. Unlike standard antibiotics, this combination leverages Relebactam, a beta-lactamase inhibitor, which helps Imipenem overcome bacterial resistance, making it potentially more effective against tough infections. Moreover, the specific focus on obese ICU patients is crucial, as these individuals often have different drug metabolism and distribution, which can affect treatment outcomes. This unique angle could lead to better-tailored therapies for a vulnerable group, improving their recovery chances.

What evidence suggests that imipenem-relebactam might be an effective treatment for obesity in ICU patients?

Research has shown that the combination of imipenem, cilastatin, and relebactam effectively treats bacterial infections, especially in challenging cases. Studies indicate that this combination spreads well throughout the body and is primarily eliminated through urine, enhancing its ability to reach and treat infections. Obesity can alter drug effectiveness, so this trial will examine the pharmacokinetics and safety of this drug combination specifically in obese ICU patients. Past studies have explored its effects in obese patients, and overall, this treatment has proven effective for bacterial infections, prompting further study in specific patient groups. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for obese ICU patients with a BMI of 40 or more, or weighing at least 120 kg. They must be adults (18+), not currently infected but in the ICU, and able to consent to the study. Exclusions include kidney issues (low creatinine clearance), current infection treatments, past study participation, known allergies to similar drugs, high serum creatinine levels, recent involvement in other drug trials, pregnancy or breastfeeding women, use of certain seizure medications.

Inclusion Criteria

Provide a signed and dated written informed consent prior to study participation

BMI ≥40 kg/m2 and/or total body weight ≥120 kg

Admitted to the ICU

Exclusion Criteria

Actively receiving antimicrobial therapy for treatment of a confirmed or suspected infection

Estimated creatinine clearance (CLCR) <60 mL/minute as determined by Cockcroft-Gault equation:

Has previously participated in this study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive multiple doses of imipenem-relebactam, with serial blood samples collected to evaluate pharmacokinetics

6 months

Multiple visits (in-person) for dosing and blood sampling

Safety Monitoring

Safety is monitored closely during study drug dosing and through 72 hours after the last dose

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Imipenem/Cilastatin
• Relebactam

Trial Overview The trial tests how obesity affects the body's handling of Imipenem-Relebactam (a combination antibiotic) given at a dose of 1.25g. It involves multiple doses and monitors non-infected obese ICU patients over time to understand this relationship.

How Is the Trial Designed?

Group I: Safety cohort Experimental Treatment 1 Intervention

After at least 2 doses of study drug, safety will be monitored closely during study drug dosing and through 72 hours after the last dose is administered in the same 12 non-infected, obese ICU patients from the PK arm

Group II: Pharmacokinetic cohort Experimental Treatment 1 Intervention

After at least 2 doses of study drug, serial blood samples will be collected from 12 non-infected, obese ICU patients to evaluate the pharmacokinetics of imipenem and relebactam in this population.

Who Is Running the Clinical Trial?

University of Illinois at Chicago

Lead Sponsor

Trials

653

Recruited

1,574,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05146154

Impact of Obesity on the Pharmacokinetics of Imipenem ... This study is an open-label, multiple-dose pharmacokinetic study of imipenem-relebactam conducted in 12 non-infected, obese ICU patients. Official Title. Impact ...

2. idse.net idse.net/Bacterial-Infections/Article/05-25/Obesity-Impact-Beta-Lactam-Antibiotics-Treatment/77266?ses=ogst

Obesity Affects PKs of Newer Beta-Lactam Combinations Obesity has been associated with treatment failure in patients receiving beta-lactam antibiotics, including novel beta-lactam/beta-lactamase ...

3. ctv.veeva.com ctv.veeva.com/study/impact-of-obesity-on-the-pharmacokinetics-of-imipenem-relebactam-in-icu-patients

Impact of Obesity on the Pharmacokinetics of Imipenem ... This study is an open-label, multiple-dose pharmacokinetic study of imipenem-relebactam conducted in 12 non-infected, obese ICU patients.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12465972/

Efficacy and safety of imipenem/cilastatin/relebactam (IMI/ ... Pharmacokinetic studies have demonstrated that IMI/CS/REL excretes primarily through the urinary tract, and that it has a good distribution in ...

5. academic.oup.com academic.oup.com/ofid/article/10/Supplement_2/ofad500.027/7448465

972. Imipenem-Cilastatin-Relebactam (I/R) Pharmacokinetics ... These are the first data to describe I/R PK in critically ill patients supported by ECMO. For patients treated with ECMO, currently labeled ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05146154

Study Details | NCT05146154 | Impact of Obesity on the ... This study is an open-label, multiple-dose pharmacokinetic study of imipenem-relebactam conducted in 12 non-infected, obese ICU patients. Official Title. Impact ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9985325/

Imipenem/cilastatin/relebactam efficacy, safety and ... To assess the relationship between renal function and efficacy/safety of imipenem/cilastatin/relebactam for the treatment of hospital-acquired/ventilator- ...

8. academic.oup.com academic.oup.com/jacamr/article-pdf/5/2/dlad011/49422577/dlad011.pdf

Imipenem/cilastatin/relebactam efficacy, safety and probability 25,26 Dose adjustment of imipenem/cilastatin/relebactam is recommended for patients with RI; full dosing of 1.25 g every 6 h is recommended for patients with ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11782751/

Real-World Experience of Imipenem–Relebactam ... In this study, the resistance rate to IMR was 2.5%, with a higher rate of 5.3% in patients admitted to the intensive care unit (ICU) compared to ...