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

NCT00934934 | Terminated Phase 2 Results

• 1 other identifier: CANTREAT
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 6

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.

Conditions

Ventilator Associated Pneumonia; Respiratory Tract Infection

Keywords

Candida; ventilator associated pneumonia; respiratory tract infection; antifungal; biomarker

Outcome Measures

Primary Outcomes (1)

• Overall Recruitment Rate

  Overall recruitment rate per site

  32 months

Secondary Outcomes (10)

• Duration of Stay in ICU

  28 days

• Ventilator Free Days

  28 days

• ICU Free Days

  28 days

• Antibiotic Free Days 28-day Post Randomization

  28 days

• Hospital Length of Stay

  90 days

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Saline will serve as the placebo solution since the active comparator is clear and colourless.

Other: Normal Saline

Antifungal

ACTIVE COMPARATOR

Patient will receive a dose daily for a total of 14 days

Drug: anidulafungin

Interventions

Normal Saline OTHER

Normal Saline

Placebo

anidulafungin DRUG

TBA

Also known as: TBA

Antifungal

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients (\>18 years old)
• In the ICU \> 48 hours
• Mechanically ventilated (\>48 hours)
• 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.
• 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

You may not qualify if:

• Patients not expected to be in ICU for more than 72 hours (due to imminent death, withdrawal of aggressive care or discharge).
• Patients with Candida spp. in the blood or another sterile body site.
• Patients colonized at other non-pulmonary body site(s) with Candida.
• Already being treated with antifungal drugs (because of documented fungal infection, pre-emptive therapy, or prophylaxis).
• Allergy to study drugs (Fluconazole or the Echinocandin on formulary at treating institution).
• 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.
• Patients with fulminant liver failure or end stage liver disease (Child's Class C).
• Women who are pregnant or lactating.
• 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).
• Prior randomization in this study.

Sponsors & Collaborators

• Daren K. Heyland: lead
• The Physicians' Services Incorporated Foundation: collaborator
• Queen's University: collaborator
• Pfizer: collaborator

Study Sites (6)

Hamilton Health Sciences Centre

Hamilton, Ontario, Canada

Location

Kingston General Hospital

Kingston, Ontario, K7L 2V7, Canada

Location

Ottawa General Hospital

Ottawa, Ontario, Canada

Location

Hopital Maisonneuve-Rosemont

Montreal, Quebec, H1T 2M4, Canada

Location

Hopital du Sacre-Coeur do Montreal

Montreal, Quebec, H4J 1C5, Canada

Location

Hopital l'Enfant-Jesus

Québec, G1J 1Z4, Canada

Location

Related Publications (33)

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  PMID: 16215368 BACKGROUND

• Muscedere JG, Martin CM, Heyland DK. The impact of ventilator-associated pneumonia on the Canadian health care system. J Crit Care. 2008 Mar;23(1):5-10. doi: 10.1016/j.jcrc.2007.11.012.

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• Van Saene H., Peric M., De La Cal M., Silvestri L.: Pneumonia during Mechanical Ventilation. Anestiologie a Intenzivni Medicina 2004; 15: 89-100.

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• Chastre J, Fagon JY. Ventilator-associated pneumonia. Am J Respir Crit Care Med. 2002 Apr 1;165(7):867-903. doi: 10.1164/ajrccm.165.7.2105078.

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• Canadian Critical Care Trials Group. A randomized trial of diagnostic techniques for ventilator-associated pneumonia. N Engl J Med. 2006 Dec 21;355(25):2619-30. doi: 10.1056/NEJMoa052904.

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• Heyland DK, Dodek P, Muscedere J, Day A, Cook D; Canadian Critical Care Trials Group. Randomized trial of combination versus monotherapy for the empiric treatment of suspected ventilator-associated pneumonia. Crit Care Med. 2008 Mar;36(3):737-44. doi: 10.1097/01.CCM.0B013E31816203D6.

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• Muscedere J, Dodek P, Keenan S, Fowler R, Cook D, Heyland D; VAP Guidelines Committee and the Canadian Critical Care Trials Group. Comprehensive evidence-based clinical practice guidelines for ventilator-associated pneumonia: prevention. J Crit Care. 2008 Mar;23(1):126-37. doi: 10.1016/j.jcrc.2007.11.014.

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• Muscedere J, Dodek P, Keenan S, Fowler R, Cook D, Heyland D; VAP Guidelines Committee and the Canadian Critical Care Trials Group. Comprehensive evidence-based clinical practice guidelines for ventilator-associated pneumonia: diagnosis and treatment. J Crit Care. 2008 Mar;23(1):138-47. doi: 10.1016/j.jcrc.2007.12.008.

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• Muscedere JG, McColl C, Shorr A, Jiang X, Marshall J, Heyland DK; Canadian Critical Care Trials Group. Determinants of outcome in patients with a clinical suspicion of ventilator-associated pneumonia. J Crit Care. 2008 Mar;23(1):41-9. doi: 10.1016/j.jcrc.2007.12.007.

  PMID: 18359420 BACKGROUND

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• Delisle MS, Williamson DR, Perreault MM, Albert M, Jiang X, Heyland DK. The clinical significance of Candida colonization of respiratory tract secretions in critically ill patients. J Crit Care. 2008 Mar;23(1):11-7. doi: 10.1016/j.jcrc.2008.01.005.

  PMID: 18359416 BACKGROUND

• Heyland et al, WATTCH database. Observational study of the clinical characteristics and biomarker profiles of 569 critically ill patients. Analysis ongoing.

  BACKGROUND

• 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.

  BACKGROUND

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• Canadian Institutes of Health Research. Available at: www.cihr.ca Accessed February 9, 2009.

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  PMID: 24981955 DERIVED

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  PMID: 21287306 DERIVED

MeSH Terms

Conditions

Pneumonia, Ventilator-Associated; Respiratory Tract Infections; Torulopsis

Interventions

Saline Solution; Anidulafungin

Condition Hierarchy (Ancestors)

Healthcare-Associated Pneumonia; Cross Infection; Infections; Pneumonia; Lung Diseases; Respiratory Tract Diseases; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Echinocandins; Peptides, Cyclic; Peptides; Amino Acids, Peptides, and Proteins

Limitations and Caveats

We had an overall enrolment rate/month of 0.6 patients/site for the randomized trial. Consequently, recruitment was halted prematurely despite efforts to optimize enrolment because of difficulty in recruiting patients and diminishing study resources.

Results Point of Contact

• Title: Dr.Daren Heyland
• Organization: CERU Queens University

dkh2@queensu.ca

403-915-5573

Study Officials

• Daren Heyland, MD

  Clinical Evaluation Research Unit

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, Clinical Evaluation Research Unit

Study Record Dates

• First Submitted: July 7, 2009
• First Posted: July 8, 2009
• Study Start: April 1, 2010
• Primary Completion: August 1, 2012
• Study Completion: August 1, 2012
• Last Updated: February 1, 2021
• Results First Posted: February 1, 2021

Record last verified: 2021-01

Locations

CA (6)