Candida in the Respiratory Tract Secretions of Critically Ill Patients and The Efficacy of Antifungal Treatment (CANTREAT)
|Ventilator Associated Pneumonia Respiratory Tract Infection||Other: Normal Saline Drug: anidulafungin||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
|Official Title:||Candida in the Respiratory Tract Secretions of Critically Ill Patients and The Efficacy of Antifungal Treatment (The CANTREAT Study): A Prospective, Randomized, Double Blind, Placebo Controlled Pilot Study|
- Feasibility will be assessed as follows: 1) Recruitment rates; 2) time required to capture required data; 3) acceptability of treatment protocol and requirement for open-label antifungal agents; 4)acceptability of laboratory procedures. [ Time Frame: 32 months ]
- Duration of stay in ICU [ Time Frame: 32 months ]
- Adjudicated diagnosis of superinfection [ Time Frame: 32 months ]
- Acquired resistance to antifungal therapy [ Time Frame: 32 months ]
- Ventilator free days [ Time Frame: 32 months ]
- ICU free days [ Time Frame: 32 months ]
- Antibiotic free days 28-day post randomization [ Time Frame: 32 months ]
- Hospital length of stay (hospital survival and 90 day mortality) [ Time Frame: 32 months ]
- Change in organ function as measured by Sequential Organ Failure Assessment (COFA) post randomization [ Time Frame: 32 months ]
- Sequential procalcitonin, C-reactive protein, interleukin-6 and B-glucan levels [ Time Frame: 32 months ]
|Study Start Date:||April 2010|
|Estimated Study Completion Date:||December 2013|
|Primary Completion Date:||August 2012 (Final data collection date for primary outcome measure)|
Placebo Comparator: Placebo
Saline will serve as the placebo solution since the active comparator is clear and colourless.
Other: Normal Saline
Active Comparator: Antifungal
Patient will receive a dose daily for a total of 14 days
Other Name: TBA
Candida spp. is commonly retrieved from microbiologic specimens of ICU patients with suspected VAP. It has been associated with increased systemic inflammation and worse clinical outcomes. This association may be due to the propensity for Candida to colonize those who are sicker, who have increased levels of systemic inflammation and worse clinical outcomes. However, an alternate possibility is that Candida is more than a colonizer and is responsible for the clinical and biochemical features observed. The only way to clarify the pathogenic role of Candida from this patient population is to treat the organism and see if patients improve compared to an untreated group. The purpose of this research program is to conduct such a study to determine if Candida in respiratory tract secretions should be routinely treated in critically ill patients. Since a definitive randomized controlled trial designed to demonstrate a reduction in mortality would be large, require the commitment of large amount of resources including both time and money, the investigators propose to first conduct a small pilot feasibility study.
Eligible patients will be randomized to receive antifungal treatment with anidulafungin or placebo. Following enrollment, study treatment (or placebo) will be started as soon as possible. When the Candida or yeast organisms have been speciated and/or a susceptibility profile is known, the study medication will be adjusted based on susceptibility patterns. The investigators propose to treat with antifungal therapy for a total of 14 days.
Patients will be followed daily for their entire stay in ICU or till day 28, whichever comes first. For patients discharged from the ICU to the ward, they will be followed until study treatment is complete (i.e. day 14). Mortality will be determined for the ICU stay, hospital stay and at 90 days. The investigators will record admission and discharge dates to ICU, step down units, and to hospital.
All patients will have 13 mL of blood/day drawn at baseline, day 3, day 8 and at the end of the treatment period on day 14 (or last day of treatment). The samples will be prepared on site and shipped to a central lab for processing. The investigators will use the blood specimens to measure markers of inflammation (C-reactive protein, Procalcitonin, and Interleukin-6 and others as determined by the investigators), markers of candida presence (b-glucan and other potential future markers) and markers of immune dysfunction (to be determined by investigators).
Please refer to this study by its ClinicalTrials.gov identifier: NCT00934934
|Hamilton Health Sciences Centre|
|Hamilton, Ontario, Canada|
|Kingston General Hospital|
|Kingston, Ontario, Canada, K7L 2V7|
|Ottawa General Hospital|
|Ottawa, Ontario, Canada|
|Montreal, Quebec, Canada, H1T 2M4|
|Hopital du Sacre-Coeur do Montreal|
|Montreal, Quebec, Canada, H4J 1C5|
|Quebec, Canada, G1J 1Z4|
|Study Chair:||Daren Heyland, MD||Clinical Evaluation Research Unit|