Candida in the Respiratory Tract Secretions of Critically Ill Patients and The Efficacy of Antifungal Treatment (CANTREAT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00934934
Recruitment Status : Terminated (slow enrollment)
First Posted : July 8, 2009
Last Update Posted : January 26, 2018
The Physicians' Services Incorporated Foundation
Queen's University
Information provided by (Responsible Party):
Daren K. Heyland, Clinical Evaluation Research Unit at Kingston General Hospital

Brief Summary:
The purpose of the study is to determine whether the effect of treating Candida spp. isolated in the respiratory tract secretions of patients with a clinical suspicion of ventilator associated pneumonia (VAP) on clinical outcomes will be feasible and supported by biomarker data obtained.

Condition or disease Intervention/treatment Phase
Ventilator Associated Pneumonia Respiratory Tract Infection Other: Normal Saline Drug: anidulafungin Phase 2

Detailed Description:

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).

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Other
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
Study Start Date : April 2010
Actual Primary Completion Date : August 2012
Actual Study Completion Date : August 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pneumonia
U.S. FDA Resources

Arm Intervention/treatment
Placebo Comparator: Placebo
Saline will serve as the placebo solution since the active comparator is clear and colourless.
Other: Normal Saline
Normal Saline
Active Comparator: Antifungal
Patient will receive a dose daily for a total of 14 days
Drug: anidulafungin
Other Name: TBA

Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. Duration of stay in ICU [ Time Frame: 32 months ]
  2. Adjudicated diagnosis of superinfection [ Time Frame: 32 months ]
  3. Acquired resistance to antifungal therapy [ Time Frame: 32 months ]
  4. Ventilator free days [ Time Frame: 32 months ]
  5. ICU free days [ Time Frame: 32 months ]
  6. Antibiotic free days 28-day post randomization [ Time Frame: 32 months ]
  7. Hospital length of stay (hospital survival and 90 day mortality) [ Time Frame: 32 months ]
  8. Change in organ function as measured by Sequential Organ Failure Assessment (COFA) post randomization [ Time Frame: 32 months ]
  9. Sequential procalcitonin, C-reactive protein, interleukin-6 and B-glucan levels [ Time Frame: 32 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Adult patients (>18 years old)
  2. In the ICU > 48 hours
  3. Mechanically ventilated (>48 hours)
  4. Grow a Candida spp. on respiratory tract secretion culture (either by Bronchoalveolar Lavage or Endotracheal Aspirate) taken on or between 48 hours before or after the day of their suspicion of respiratory tract infection.
  5. Develop a clinical suspicion of respiratory tract infection while ventilated as defined by the following criteria (as defined previously in our VAP trial)5:

    • The presence of new, worsening or persistent radiographic features suggestive of pneumonia without another obvious cause AND
    • The presence of any two of the following:

      • Fever > 38C (core temperature)
      • Leukocytosis (>11.0 x109/L) or neutropenia (<3.5 x109/L)
      • Purulent endotracheal aspirates or change in character of aspirates
      • Isolation of pathogenic bacteria from endotracheal aspirates
      • Increasing oxygen requirements

Exclusion Criteria:

  1. Patients not expected to be in ICU for more than 72 hours (due to imminent death, withdrawal of aggressive care or discharge).
  2. Patients with Candida spp. in the blood or another sterile body site.
  3. Patients colonized at other non-pulmonary body site(s) with Candida.
  4. Already being treated with antifungal drugs (because of documented fungal infection, pre-emptive therapy, or prophylaxis).
  5. Allergy to study drugs (Fluconazole or the Echinocandin on formulary at treating institution).
  6. Immunocompromised patients (post-organ transplantation, Acquired Immunodeficiency Syndrome [AIDS], neutropenia [<1000 absolute neutrophils], corticosteroids [>20 mgs/day of prednisone or equivalent for more than 6 months]). These patients are excluded since Candida may be more invasive and these patients are much more likely to require systemic antifungal therapy.
  7. Patients with fulminant liver failure or end stage liver disease (Child's Class C).
  8. Women who are pregnant or lactating.
  9. Enrollment in industry sponsored interventional trial (co-enrollment in other academic studies would be allowed with the proviso that there was no potential interaction between the protocols).
  10. Prior randomization in this study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00934934

Canada, Ontario
Hamilton Health Sciences Centre
Hamilton, Ontario, Canada
Kingston General Hospital
Kingston, Ontario, Canada, K7L 2V7
Ottawa General Hospital
Ottawa, Ontario, Canada
Canada, Quebec
Hopital Maisonneuve-Rosemont
Montreal, Quebec, Canada, H1T 2M4
Hopital du Sacre-Coeur do Montreal
Montreal, Quebec, Canada, H4J 1C5
Hopital l'Enfant-Jesus
Quebec, Canada, G1J 1Z4
Sponsors and Collaborators
Daren K. Heyland
The Physicians' Services Incorporated Foundation
Queen's University
Study Chair: Daren Heyland, MD Clinical Evaluation Research Unit

Van Saene H., Peric M., De La Cal M., Silvestri L.: Pneumonia during Mechanical Ventilation. Anestiologie a Intenzivni Medicina 2004; 15: 89-100.
Heyland et al, WATTCH database. Observational study of the clinical characteristics and biomarker profiles of 569 critically ill patients. Analysis ongoing.
Williamson D., Martin A., Perreault M., Delisle M., Muscedere J., Rotstein C., Jiang X., Heyland D. Impact of pulmonary Candida colonization on systemic inflammation in the critically ill. Manuscript in preparation.
Williamson D., Albert M., Perreault M., Delisle M., Muscedere J., Rotstein C.Jiang X., Day A. ,Heyland D. Effect of Candida spp. in respiratory tract secretions on systemic inflammation. Submitted to SCCM for Feb. 2009
Canadian Institutes of Health Research. Available at: Accessed February 9, 2009.

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Daren K. Heyland, Director, Clinical Evaluation Research Unit, Clinical Evaluation Research Unit at Kingston General Hospital Identifier: NCT00934934     History of Changes
Other Study ID Numbers: CANTREAT
First Posted: July 8, 2009    Key Record Dates
Last Update Posted: January 26, 2018
Last Verified: January 2018

Keywords provided by Daren K. Heyland, Clinical Evaluation Research Unit at Kingston General Hospital:
ventilator associated pneumonia
respiratory tract infection

Additional relevant MeSH terms:
Critical Illness
Respiratory Tract Infections
Pneumonia, Ventilator-Associated
Lung Diseases
Respiratory Tract Diseases
Disease Attributes
Pathologic Processes
Cross Infection
Ventilator-Induced Lung Injury
Lung Injury
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP2C9 Inhibitors
Cytochrome P-450 CYP3A Inhibitors