Efficacy of Colistin Monotherapy Versus Colistin Plus Minocycline for Carbapenem-Resistant A. Baumannii Infection

Acinetobacter Infections Clinical Trial

Official title:

Efficacy of Colistin Monotherapy Versus Colistin Plus Minocycline for Therapy of Carbapenem-Resistant Acinetobacter Baumannii Infection

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05586815
• Other study ID #: SI-CEU-03-2022
• Status: Recruiting
• Phase: Phase 4
• Start date: January 10, 2023
• Est. completion date: June 30, 2024

Study information

• Verified date: January 2023
• Source: Mahidol University
• Contact: Adhiratha Boonyasiri, MD
• Phone: +66850632181
• Email: adhiratha.bon[@]mahidol.ac.th
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Acinetobacter baumannii causes severe infections (pneumonia, bacteremia, organ space) with high lethality in hospitalised critically ill patients. It can acquire resistance to all classes of antibiotics (multidrug resistance, MDR) except an 'old' drug, colistin, which may be the only therapeutic option. The addition of minocycline to colistin has been shown to be synergistic in vitro, and may be promising in vivo, but this combination has not been limited to case report or case series in comparison with colistin alone.

Description:

The purpose of this double-blind, randomized, parallel, placebo-controlled clinical trial is to assess whether the association of colistin and minocycline reduces significantly the mortality of patients with severe MDR A. baumannii infections compared with colistin alone.

The trial will enroll 94 patients from internal medicine ward and intensive care units (ICU) of an university care hospitals where MDR A. baumannii infection is endemic with epidemic phases. Patients will be randomly allocated to either colistin plus placebo (control arm) or colistin plus minocycline (experimental arm).

Primary end point is overall mortality, defined as death occurring within 28 days from randomisation.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 94
• Est. completion date: June 30, 2024
• Est. primary completion date: January 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 95 Years

Eligibility

Inclusion Criteria:

• Clinical and microbiological evidence of a severe infection due to multi-drug resistant A. baumannii during hospitalization

• Susceptibility of the A. baumannii isolate to colistin (MIC < or =2 mg/l).

Exclusion Criteria:

• Treatment with one of the study drugs prior to the diagnosis of A. baumannii infection more than 48 hours

• Severe liver dysfunction

• History of prior hypersensitivity to the study drugs

• Pregnancy and lactation

Related Conditions & MeSH terms

• Acinetobacter Infections
• Communicable Diseases
• Infections

Intervention

Drug:
• Colistin
150 mg every 8 hours intravenously for at least 7 and up to a maximum of 28 days
• Minocycline
200 mg every 12 hours orally for at least 7 and up to a maximum of 28 days
• Placebo
Capsule without active compound

Locations

Country	Name	City	State
Thailand	Faculty of Medicine Siriraj Hospital, Mahidol University	Bangkok

Sponsors (1)

Lead Sponsor	Collaborator
Mahidol University

Country where clinical trial is conducted

Thailand, 

References & Publications (2)

Koomanachai P, Tiengrim S, Kiratisin P, Thamlikitkul V. Efficacy and safety of colistin (colistimethate sodium) for therapy of infections caused by multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii in Siriraj Hospital, Bangkok, Thailand. Int J Infect Dis. 2007 Sep;11(5):402-6. doi: 10.1016/j.ijid.2006.09.011. Epub 2007 Feb 8. — View Citation

Thamlikitkul V, Tiengrim S, Seenama C. Comparative in vitro activity of minocycline and selected antibiotics against carbapenem-resistant Acinetobacter baumannii from Thailand. Int J Antimicrob Agents. 2016 Jan;47(1):101-2. doi: 10.1016/j.ijantimicag.2015.11.006. Epub 2015 Dec 11. No abstract available. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	All cause mortality	The study primary outcome is patient overall mortality, defined as death occurring during hospitalisation or within 28 days from randomization.	28 days
Secondary	Microbiological eradication	Microbiological eradication is defined as the disappearance of A. baumannii in cultures from blood, bronchial aspirate, urines and drainage fluids.	28 days
Secondary	Incidence of Renal toxicity (safety)	Renal toxicity is defined as decrease of creatinine clearance below 50 ml/min or >50% reduction in the creatinine clearance relative to the baseline.	28 days
Secondary	Incidence of Hepatic toxicity (safety)	Hepatic toxicity is defined as increase of direct bilirubin above 3 mg/dl.	28 days