Vancomycin Dose Optimization in Obesity

NCT06601257 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: HUM0025644475F40122C00147
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn how to optimize vancomycin dosing in obese adults based on weight and kidney function. It will also assess the safety of different vancomycin dosing strategies. The main questions it aims to answer are: Does dosing vancomycin based on kidney function provide better drug exposure than dosing based on weight? What medical or safety issues arise when vancomycin is dosed according to weight versus kidney function? Participants will be randomized into two groups. One group will receive vancomycin doses based on their weight, while the other will receive doses based on their kidney function. Participants will: Receive a single dose of vancomycin based on either their weight or kidney function after pretreatment with antihistamines Provide blood and urine samples at specific times for pharmacokinetic analysis Undergo body composition measurements using DEXA scans and other methods Visit the clinic for physical exams, medical history, and laboratory tests

Conditions

Pharmacokinetics and Pharmacodynamics

Keywords

obesity; pharmacokinetics; vancomycin; antibiotics; body composition; kidney function; renal

Outcome Measures

Primary Outcomes (1)

• Probability of target attainment

  Number of participants with a vancomycin area under the concentration-time curve that is between 400 h\*mg/L and 600 h\*mg/L after a single dose.

  24 hours

Study Arms (2)

Control

ACTIVE COMPARATOR

Weight-stratified dosing as the current standard of care

Drug: Vancomycin (IV)

Test

EXPERIMENTAL

Kidney function stratified dosing

Drug: Vancomycin (IV)

Interventions

Vancomycin (IV) DRUG

Vancomycin weight-based or kidney function-based dosing

Control; Test

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• healthy obese participants within three obese class groups; BMI 30-34.9 kg/m2 (n=8), BMI 35-39.9 kg/m2 (n=8), and BMI ≥ 40 kg/m2 (n=8)
• Male or female adults age 18 to 50 years
• Weight ≥ 80 kg
• Estimated creatinine clearance of 60 mL/min to 119 mL/min (n=12) or ≥ 120 mL/min (n=12) (based on the Cockcroft-Gault equation and dosing weight)

You may not qualify if:

• Pregnant or lactating females
• Significant clinical illness within 3 weeks prior to screening
• History of severe allergic diseases including drug allergies, with the exception of seasonal allergies
• Patients initiated on GLP1 agonists
• Any other factor, condition, or disease, including but not limited to cardiovascular, renal, hepatic, or gastrointestinal disorders that may, in the opinion of the Investigator, jeopardize the safety of the participant or impact the validity of the study results.
• History of drug addiction or alcohol abuse within the past 12 months
• Any clinically significant abnormal lab values (Chemistry and Complete Blood Count) during screening
• Participants unwilling or unable to receive vancomycin by intravenous infusion
• Individuals with a history of psychiatric or neurological illness, including seizure disorders
• Systolic blood pressure less than 90 mm of Hg or more than 140 mm of Hg
• Diastolic blood pressure less than 60 mm of Hg or more than 90 mm of Hg
• Pulse rate \<50 beats/minute or \>100 beats/minute.
• History of hypersensitivity or infusion reaction to vancomycin, cetirizine, or famotidine
• Participants with underlying hearing loss
• Participants that are taking ototoxic drugs

Sponsors & Collaborators

• University of Michigan: lead

Study Sites (1)

Michigan Clinical Research Unit

Ann Arbor, Michigan, 48108, United States

RECRUITING

Related Publications (5)

• Pai MP. Antimicrobial Dosing in Specific Populations and Novel Clinical Methodologies: Kidney Function. Clin Pharmacol Ther. 2021 Apr;109(4):952-957. doi: 10.1002/cpt.2179. Epub 2021 Mar 3.

  PMID: 33523498 BACKGROUND

• Pai MP. Antimicrobial Dosing in Specific Populations and Novel Clinical Methodologies: Obesity. Clin Pharmacol Ther. 2021 Apr;109(4):942-951. doi: 10.1002/cpt.2181. Epub 2021 Feb 28.

  PMID: 33523485 BACKGROUND

• Pai MP, Derstine BA, Lichty M, Ross BE, Sullivan JA, Su GL, Wang SC. Relationships of Vancomycin Pharmacokinetics to Body Size and Composition Using a Novel Pharmacomorphomic Approach Based on Medical Imaging. Antimicrob Agents Chemother. 2017 Oct 24;61(11):e01402-17. doi: 10.1128/AAC.01402-17. Print 2017 Nov.

  PMID: 28807918 BACKGROUND

• Crass RL, Dunn R, Hong J, Krop LC, Pai MP. Dosing vancomycin in the super obese: less is more. J Antimicrob Chemother. 2018 Nov 1;73(11):3081-3086. doi: 10.1093/jac/dky310.

  PMID: 30203073 BACKGROUND

• Rybak MJ, Le J, Lodise TP, Levine DP, Bradley JS, Liu C, Mueller BA, Pai MP, Wong-Beringer A, Rotschafer JC, Rodvold KA, Maples HD, Lomaestro BM. Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: A revised consensus guideline and review by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists. Am J Health Syst Pharm. 2020 May 19;77(11):835-864. doi: 10.1093/ajhp/zxaa036. No abstract available.

  PMID: 32191793 BACKGROUND

MeSH Terms

Conditions

Obesity

Interventions

Vancomycin

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins

Central Study Contacts

Amit Pai, PharmD

CONTACT

7346470006; amitpai@med.umich.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 11, 2024
• First Posted: September 19, 2024
• Study Start: April 1, 2025
• Primary Completion: March 31, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: May 30, 2025

Record last verified: 2025-05

Locations

US (1)