Acinetobacter Infections
Conditions
Keywords
colistin, minocycline, carbapenem-resistant Acinetobacter baumannii
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.
Interventions
DRUGColistin
150 mg every 8 hours intravenously for at least 7 and up to a maximum of 28 days
DRUGMinocycline
200 mg every 12 hours orally for at least 7 and up to a maximum of 28 days
DRUGPlacebo
Capsule without active compound
Sponsors
Mahidol University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Double blind, Placebo Controlled
Intervention model description
A Phase 4 Randomized, Double blind, Placebo Controlled
Eligibility
Sex/Gender
ALL
Age
18 Years to 95 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Thailand
Contacts
Primary ContactAdhiratha Boonyasiri, MD
Outcome results
None listed