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

This study has been terminated.
(slow enrollment)
Sponsor:
Collaborators:
The Physicians' Services Incorporated Foundation
Queen's University
Pfizer
Information provided by (Responsible Party):
Daren K. Heyland, Clinical Evaluation Research Unit at Kingston General Hospital
ClinicalTrials.gov Identifier:
NCT00934934
First received: July 7, 2009
Last updated: July 31, 2013
Last verified: July 2013
  Purpose

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 Intervention Phase
Ventilator Associated Pneumonia
Respiratory Tract Infection
Other: Normal Saline
Drug: anidulafungin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Clinical Evaluation Research Unit at Kingston General Hospital:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Duration of stay in ICU [ Time Frame: 32 months ] [ Designated as safety issue: No ]
  • Adjudicated diagnosis of superinfection [ Time Frame: 32 months ] [ Designated as safety issue: No ]
  • Acquired resistance to antifungal therapy [ Time Frame: 32 months ] [ Designated as safety issue: No ]
  • Ventilator free days [ Time Frame: 32 months ] [ Designated as safety issue: No ]
  • ICU free days [ Time Frame: 32 months ] [ Designated as safety issue: No ]
  • Antibiotic free days 28-day post randomization [ Time Frame: 32 months ] [ Designated as safety issue: No ]
  • Hospital length of stay (hospital survival and 90 day mortality) [ Time Frame: 32 months ] [ Designated as safety issue: No ]
  • Change in organ function as measured by Sequential Organ Failure Assessment (COFA) post randomization [ Time Frame: 32 months ] [ Designated as safety issue: No ]
  • Sequential procalcitonin, C-reactive protein, interleukin-6 and B-glucan levels [ Time Frame: 32 months ] [ Designated as safety issue: No ]

Enrollment: 60
Study Start Date: April 2010
Estimated Study Completion Date: December 2013
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
TBA
Other Name: TBA

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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00934934

Locations
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 du Sacre-Coeur do Montreal
Montreal, Quebec, Canada, H4J 1C5
Hopital Maisonneuve-Rosemont
Montreal, Quebec, Canada, H1T 2M4
Canada
Hopital l'Enfant-Jesus
Quebec, Canada, G1J 1Z4
Sponsors and Collaborators
Daren K. Heyland
The Physicians' Services Incorporated Foundation
Queen's University
Pfizer
Investigators
Study Chair: Daren Heyland, MD Clinical Evaluation Research Unit
  More Information

Publications:
Muscedere J., Martin C., Heyland D. The Direct burden of Illness from Ventilator Associated Pneumonia. J of Critical Care, 2008; 23: 5-10.
Van Saene H., Peric M., De La Cal M., Silvestri L.: Pneumonia during Mechanical Ventilation. Anestiologie a Intenzivni Medicina 2004; 15: 89-100.
Chastre J. Fagon J. Ventilator-Associated Pneumonia. Am. J. of Respir Crit Care Med. 2002; 165: 867- 903.
Heyland D., Dodek P., Day A. Muscedere J., Cook D. for the Canadian Critical Care Trials Group. A Randomized Trial Of Diagnostic Techniques For Suspected Ventilator-Associated Pneumonia. New Eng J of Medicine, N Engl J Med 2006;355:2619-30.
Chastre J. Fagon JY. Ventilator-associated pneumonia. American Journal of Respiratory & Critical Care Medicine. 2002; 165:867-903.
Reade M., Angus D. The clinical research enterprise in critical care: What's right, what's wrong and what's ahead. Critical Care Medicine 2009; 37(1S): S1-S9.
Van An Teijlingen E., Hundley V. The importance of pilot studies. Nursing Standard 2002; 16: 33-36.
Arnold D., Burns K., Adhikari N., Kho M., Meade M., Cook D. et al. The design and interpretation of pilot trials in clinical research in critical care. Critical Care Medicine 2009; 37(Suppl.):S69-74.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Daren K. Heyland, Director, Clinical Evaluation Research Unit, Clinical Evaluation Research Unit at Kingston General Hospital
ClinicalTrials.gov Identifier: NCT00934934     History of Changes
Other Study ID Numbers: CANTREAT
Study First Received: July 7, 2009
Last Updated: July 31, 2013
Health Authority: Canada: Health Canada

Keywords provided by Clinical Evaluation Research Unit at Kingston General Hospital:
Candida
ventilator associated pneumonia
respiratory tract infection
antifungal
biomarker

Additional relevant MeSH terms:
Critical Illness
Infection
Pneumonia
Pneumonia, Ventilator-Associated
Respiratory Tract Infections
Cross Infection
Disease Attributes
Lung Diseases
Lung Injury
Pathologic Processes
Respiratory Tract Diseases
Ventilator-Induced Lung Injury
Anidulafungin
Antifungal Agents
Miconazole
14-alpha Demethylase Inhibitors
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014