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

Study Overview
=================
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.

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.

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

Conditions
-----------------
Acinetobacter Infections

Intervention / Treatment
-----------------
* Drug: Colistin
* Drug: Minocycline
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 95 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A Phase 4 Randomized, Double blind, Placebo Controlled
Masking: Double


Arms and Interventions

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

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microbiological eradication | Microbiological eradication is defined as the disappearance of A. baumannii in cultures from blood, bronchial aspirate, urines and drainage fluids. | 28 days | 
| 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 | 
| Incidence of Hepatic toxicity (safety) | Hepatic toxicity is defined as increase of direct bilirubin above 3 mg/dl. | 28 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
colistin, minocycline, carbapenem-resistant Acinetobacter baumannii