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

Sponsor

Mahidol University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05586815

Collaborator

(none)

Enrollment

Location

Arms

17.6

Anticipated Duration (Months)

5.3

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Acinetobacter Infections	Drug: Colistin Drug: Minocycline Drug: Placebo	Phase 4

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

94 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

A Phase 4 Randomized, Double blind, Placebo ControlledA Phase 4 Randomized, Double blind, Placebo Controlled

Masking:

Double (Participant, Investigator)

Masking Description:

Double blind, Placebo Controlled

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jan 10, 2023

Anticipated Primary Completion Date :

Jan 31, 2024

Anticipated Study Completion Date :

Jun 30, 2024

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Colistin plus Placebo Colistin alone, 150 mg every 8 hours intravenously or according to renal function, plus Placebo	Drug: Colistin 150 mg every 8 hours intravenously for at least 7 and up to a maximum of 28 days Other Names: Sodium colistimethate Drug: Placebo Capsule without active compound
Experimental: Colistin plus Minocycline Colistin, 150 mg every 8 hours intravenously or according to renal function, plus Minocycline, 200 mg every 12 hours orally	Drug: Colistin 150 mg every 8 hours intravenously for at least 7 and up to a maximum of 28 days Other Names: Sodium colistimethate Drug: Minocycline 200 mg every 12 hours orally for at least 7 and up to a maximum of 28 days Other Names: Mino

Arm

Intervention/Treatment

Active Comparator: Colistin plus Placebo

Colistin alone, 150 mg every 8 hours intravenously or according to renal function, plus Placebo

Drug: Colistin

150 mg every 8 hours intravenously for at least 7 and up to a maximum of 28 days

Other Names:

Sodium colistimethate

Drug: Placebo

Capsule without active compound

Experimental: Colistin plus Minocycline

Colistin, 150 mg every 8 hours intravenously or according to renal function, plus Minocycline, 200 mg every 12 hours orally

Drug: Colistin

150 mg every 8 hours intravenously for at least 7 and up to a maximum of 28 days

Other Names:

Sodium colistimethate

Drug: Minocycline

200 mg every 12 hours orally for at least 7 and up to a maximum of 28 days

Other Names:

Mino

Outcome Measures

Primary Outcome Measures

All cause mortality [28 days]
The study primary outcome is patient overall mortality, defined as death occurring during hospitalisation or within 28 days from randomization.

Secondary Outcome Measures

Microbiological eradication [28 days]
Microbiological eradication is defined as the disappearance of A. baumannii in cultures from blood, bronchial aspirate, urines and drainage fluids.
Incidence of Renal toxicity (safety) [28 days]
Renal toxicity is defined as decrease of creatinine clearance below 50 ml/min or >50% reduction in the creatinine clearance relative to the baseline.
Incidence of Hepatic toxicity (safety) [28 days]
Hepatic toxicity is defined as increase of direct bilirubin above 3 mg/dl.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 95 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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