Therapeutic Drug Monitoring in Patients With Difficult-to-Treat Gram-Negative Bacterial Infections

NCT05942157 | Unknown DMC

• 1 other identifier: TDM RCT
• Study Type: interventional
• Target: 810
• Locations: 1 country
• Sites: 1

Brief Summary

A prospective, open-label, randomized controlled trial will be conducted to evaluate a novel TDM-guided therapy in management of DT-GNB infections. We hypothesize that TDM-guided antibiotic therapy will reduce 14-day all-cause mortality by 6% (absolute risk reduction) in septic patients with DT-GNB infections, when compared to standard therapy. TDM for 11 antibiotics will be performed for all trial patients although test information will be withheld for the standard therapy arm. The primary aim is to compare the 14-day all-cause mortality rates of novel TDM-guided antibiotic dosing versus standard therapy.

Conditions

Sepsis; Hemodynamic Instability; Bacterial Infections; Therapeutic Drug Monitoring; Antimicrobial Resistance

Keywords

Sepsis; Hemodynamic Instability; Therapeutic Drug Monitoring; Gram-negative Bacteria; Beta-Lactams; Fosfomycin; Fluoroquinolone; Glycylcycline; Dialysis

Outcome Measures

Primary Outcomes (1)

• 14-day All-Cause Mortality Rate

  This is defined as death of any cause. Study aims to compare the difference in 14-day all-cause mortality rates from the day of randomization between both arms.

  14 Days

Secondary Outcomes (4)

• Fever Resolution

  14 Days

• Microbiological Treatment Cure of Difficult to Treat Gram-Negative Bacteria (DT-GNB)

  14 Days

• Improved or Stabilized Sequential Organ Failure Assessment (SOFA)

  14 Days

• Incidences of Adverse Drug Reactions

  Start to End of Antibiotic Therapy (Up to 90 days from randomization, discharge or demise, whichever comes earliest)

Study Arms (2)

Control

NO INTERVENTION

The prescription of antibiotics will follow institution antibiotic prescribing guidelines or at the Infectious Disease (ID) clinician's discretion, based on culture and antibiotic susceptibilities results (whenever available). Empiric antibiotic treatment will be employed prior to the availability of culture or antibiotic susceptibilities results. Antibiotic level measurements, Minimum Inhibitory Concentrations (MIC) testing and Pharmacokinetics/Pharmacodynamics (PK/PD) target analysis will only be performed at Day 14 post enrolment, but the results will not be released to the ID clinician and the primary clinician.

Intervention

EXPERIMENTAL

Once a positive GNB culture is known, antibiotic MIC testing will commence, and PK/PD target analysis will be performed using the antibiotic MIC. An every-other-day TDM-guided regimen will be chosen to rapidly adjust the antibiotic doses until the PK/PD target is achieved. In the event the antibiotic dose readjustment is unable to achieve the defined PK/PD target, blood sampling will continue every other day until Day 14 or the PK/PD target is achieved

Other: Therapeutic Drug Monitoring (TDM)

Interventions

Therapeutic Drug Monitoring (TDM) OTHER

Upon randomization and before the bacterial culture results are known, blood sampling will be obtained from the patient during the morning round of initial empiric antibiotic administration. PK/PD target analysis based on the clinical susceptibility breakpoints of Enterobacterales (the most prevalent organism family of DT-GNB infections in our setting) will be performed and a dosage recommendation will be communicated to the primary ID clinician. Antibiotic dosing adjustments (if any) will be made within 8 - 24 hours of the blood sampling by the Primary / Infectious Diseases clinician. In case of inappropriate dosing, where the PK/PD target is not achieved or exceeded with antibiotic side effects observed, the dosage will be increased or decreased, respectively.

Intervention

Eligibility Criteria

• Age: 16 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• years or older
• Receive intravenous therapy of the study antibiotics

You may not qualify if:

• Pregnancy
• Antibiotics cessation before first blood sample collection
• Receiving antibiotics only as prophylaxis
• On palliative care or with less than 48 hours of life expectancy

Sponsors & Collaborators

• Singapore General Hospital: lead

Study Sites (1)

Singapore General Hospital

Singapore, 168582, Singapore

RECRUITING

MeSH Terms

Conditions

Sepsis; Bacterial Infections

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Bacterial Infections and Mycoses

Study Officials

• Tze Peng Lim, PhD

  Singapore General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tze Peng Lim, PhD

CONTACT

+65 6326 6959; lim.tze.peng@sgh.com.sg

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2023
• First Posted: July 12, 2023
• Study Start: March 29, 2023
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: July 19, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)