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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Colistin plus Placebo | Active Comparator | Colistin alone, 150 mg every 8 hours intravenously or according to renal function, plus Placebo |
|
| Colistin plus Minocycline | Experimental | Colistin, 150 mg every 8 hours intravenously or according to renal function, plus Minocycline, 200 mg every 12 hours orally |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Colistin | Drug | 150 mg every 8 hours intravenously for at least 7 and up to a maximum of 28 days |
|
| 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 |
| 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) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Adhiratha Boonyasiri, MD | Contact | +66850632181 | adhiratha.bon@mahidol.ac.th |
| Name | Affiliation | Role |
|---|---|---|
| Adhiratha Boonyasiri, MD | Mahidol University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Faculty of Medicine Siriraj Hospital, Mahidol University | Recruiting | Bangkok | 10700 | Thailand |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 17291803 | Background | 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. | |
| 26725031 |
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| ID | Term |
|---|---|
| D000151 | Acinetobacter Infections |
| C562573 | cyclopia sequence |
| ID | Term |
|---|---|
| D045828 | Moraxellaceae Infections |
| D016905 | Gram-Negative Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
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| ID | Term |
|---|---|
| D003091 | Colistin |
| C004691 | colistinmethanesulfonic acid |
| D008911 | Minocycline |
| ID | Term |
|---|---|
| D011113 | Polymyxins |
| D010456 | Peptides, Cyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
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A Phase 4 Randomized, Double blind, Placebo Controlled
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Double blind, Placebo Controlled
| Minocycline | Drug | 200 mg every 12 hours orally for at least 7 and up to a maximum of 28 days |
|
|
| Placebo | Drug | Capsule without active compound |
|
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 |
| 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. |
| D007239 | Infections |
| D055666 |
| Lipopeptides |
| D008055 | Lipids |
| D023181 | Antimicrobial Cationic Peptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D000089882 | Antimicrobial Peptides |
| D052899 | Pore Forming Cytotoxic Proteins |
| D008565 | Membrane Proteins |
| D011506 | Proteins |
| D013754 | Tetracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |