TerminatedNCT00934934CANTREATUpdated Feb 1, 2021Results posted

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

A Phase 2 interventional study of Normal Saline and anidulafungin in Ventilator Associated Pneumonia and Respiratory Tract Infection, sponsored by Daren K. Heyland. Terminated at 6 sites in Canada. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-02-01.

Sponsored by Daren K. Heyland · Phase 2, Interventional, and Other

Why this study was terminated

slow enrollment

Phase: Phase 2
Study type: Interventional
Enrollment: 61
Allocation: Randomized
Ages: 18 Years and older
Sex: All

Study 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.

Read the 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).

Conditions studied

Ventilator Associated Pneumonia
Respiratory Tract Infection

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Keywords

Candida
ventilator associated pneumonia
respiratory tract infection
antifungal
biomarker

In context

Pneumonia

2,044 studies on the registry are indexed under Pneumonia; 283 are open to participants now.

This study's enrollment of 61 is below the median of 106 across 1,247 interventional studies indexed under Pneumonia.

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Lead sponsor

Daren K. Heyland is the lead sponsor of 10 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

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

Exclusion criteria

Exclusion Criteria:

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.

Study design

Phase: Phase 2
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 61 participants (actual)

Study arms

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
Drug: anidulafungin

Interventions

OtherNormal Saline
Normal Saline
Druganidulafungin
TBA
Also known as: TBA

What researchers measure

Primary outcomes

Overall Recruitment Rate
Overall recruitment rate per site
Time frame: 32 months

Secondary outcomes

Duration of Stay in ICU
Measure of the duration of participant stay in the ICU
Time frame: 28 days
Ventilator Free Days
Number of days in ICU free of ventilation
Time frame: 28 days
ICU Free Days
Number of days free of ICU
Time frame: 28 days
Antibiotic Free Days 28-day Post Randomization
Number of days free of antibiotic use within the first 28 days
Time frame: 28 days
Hospital Length of Stay
Measure of the duration of the participant's hospital stay
Time frame: 90 days
(SOFA) Post Randomization
Sequential organ failure assessment. 0-24 The higher the number the more severe organ failure
Time frame: post randomization
Sequential Procalcitonin
Time frame: 28 days
C-reactive Protein
Time frame: 28 days
Interleukin-6
Time frame: 28 days
B-glucan Levels
Time frame: 28 days

Results

Posted Feb 1, 2021

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.

Participant flow

Participant flow — Overall Study
Milestone	Placebo	Antifungal
Started	30	31
Completed	29	31
Not completed	1	0

Outcome measures

PrimaryOverall Recruitment Rate

Overall recruitment rate per site

Time frame:: 32 months
Reported as:: Number · participants per site /month

Overall Recruitment Rate
participants per site /month	Overall
Overall Recruitment Rate	0.6

SecondaryDuration of Stay in ICU

Measure of the duration of participant stay in the ICU

Time frame:: 28 days
Reported as:: Median · days

Duration of Stay in ICU
days	Placebo	Antifungal
Duration of Stay in ICU	11.5 (8 to 20)	13 (8 to 28)

SecondaryVentilator Free Days

Number of days in ICU free of ventilation

Time frame:: 28 days
Reported as:: Median · days

Ventilator Free Days
days	Placebo	Antifungal
Ventilator Free Days	8 (6 to 11)	9 (4 to 10)

SecondaryICU Free Days

Number of days free of ICU

Time frame:: 28 days
Reported as:: Median · days

ICU Free Days
days	Placebo	Antifungal
ICU Free Days	14 (0 to 17)	4 (0 to 17)

SecondaryAntibiotic Free Days 28-day Post Randomization

Number of days free of antibiotic use within the first 28 days

Time frame:: 28 days
Reported as:: Median · days

Antibiotic Free Days 28-day Post Randomization
days	Placebo	Antifungal
Antibiotic Free Days 28-day Post Randomization	16 (12 to 20)	10 (0 to 20)

SecondaryHospital Length of Stay

Measure of the duration of the participant's hospital stay

Time frame:: 90 days
Reported as:: Median · days

Hospital Length of Stay
days	Placebo	Antifungal
Hospital Length of Stay	29 (17 to 38)	28 (18 to 46)

Secondary(SOFA) Post Randomization

Sequential organ failure assessment. 0-24 The higher the number the more severe organ failure

Time frame:: post randomization
Reported as:: Mean · score on a scale

(SOFA) Post Randomization
score on a scale	Placebo	Antifungal
(SOFA) Post Randomization	5.9 ± 3.3	5.9 ± 3.6

SecondarySequential Procalcitonin

Time frame:: 28 days
Reported as:: Mean · ng/ml

Sequential Procalcitonin
ng/ml	VAP withCandida	VAP Without Candida
Sequential Procalcitonin	3.0 ± 8.8	22.5 ± 89.4

SecondaryC-reactive Protein

Time frame:: 28 days
Reported as:: Mean · mg/l

C-reactive Protein
mg/l	VAP withCandida	VAP Without Candida
C-reactive Protein	133 ± 115	145.7 ± 104

SecondaryInterleukin-6

Time frame:: 28 days
Reported as:: Mean · pg/ml

Interleukin-6
pg/ml	VAP withCandida	VAP Without Candida
Interleukin-6	97.5 ± 183	3 ± 10.3

SecondaryB-glucan Levels

Time frame:: 28 days
Reported as:: Mean · pg/ml

B-glucan Levels
pg/ml	VAP withCandida	VAP Without Candida
B-glucan Levels	116 ± 171	129.1 ± 190.5

Adverse events

Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Placebo	—	—	—
Antifungal	—	—	—

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Placebo	Antifungal	Total
Mean	63.0 ± 13.8	57.6 ± 17.1	60.3 ± 15.5

Sex: Female, Male
Sex: Female, Male(Participants)	Placebo	Antifungal	Total
Female	6	10	16
Male	23	21	44

Region of Enrollment
Region of Enrollment(participants)	Placebo	Antifungal	Total
Canada	29	31	60

Study locations

6 sites

Hamilton Health Sciences Centre
Hamilton, Ontario, Canada
Kingston General Hospital
Kingston, Ontario K7L 2V7, Canada
Ottawa General Hospital
Ottawa, Ontario, Canada
Hopital Maisonneuve-Rosemont
Montreal, Quebec H1T 2M4, Canada
Hopital du Sacre-Coeur do Montreal
Montreal, Quebec H4J 1C5, Canada
Hopital l'Enfant-Jesus
Quebec, G1J 1Z4, Canada

References and documents

Publications

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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. PubMed 18359430 ↗
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Rello J, Esandi ME, Diaz E, Mariscal D, Gallego M, Valles J. The role of Candida sp isolated from bronchoscopic samples in nonneutropenic patients. Chest. 1998 Jul;114(1):146-9. doi: 10.1378/chest.114.1.146. PubMed 9674461 ↗
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Wheeler RT, Fink GR. A drug-sensitive genetic network masks fungi from the immune system. PLoS Pathog. 2006 Apr;2(4):e35. doi: 10.1371/journal.ppat.0020035. Epub 2006 Apr 28. PubMed 16652171 ↗
Azoulay E, Timsit JF, Tafflet M, de Lassence A, Darmon M, Zahar JR, Adrie C, Garrouste-Orgeas M, Cohen Y, Mourvillier B, Schlemmer B; Outcomerea Study Group. Candida colonization of the respiratory tract and subsequent pseudomonas ventilator-associated pneumonia. Chest. 2006 Jan;129(1):110-7. doi: 10.1378/chest.129.1.110. PubMed 16424420 ↗
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. PubMed 18359416 ↗
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.
Magill SS, Swoboda SM, Johnson EA, Merz WG, Pelz RK, Lipsett PA, Hendrix CW. The association between anatomic site of Candida colonization, invasive candidiasis, and mortality in critically ill surgical patients. Diagn Microbiol Infect Dis. 2006 Aug;55(4):293-301. doi: 10.1016/j.diagmicrobio.2006.03.013. Epub 2006 May 15. Erratum In: Diagn Microbiol Infect Dis. 2007 Mar;57(3):351. PubMed 16698215 ↗
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Nseir S, Jozefowicz E, Cavestri B, Sendid B, Di Pompeo C, Dewavrin F, Favory R, Roussel-Delvallez M, Durocher A. Impact of antifungal treatment on Candida-Pseudomonas interaction: a preliminary retrospective case-control study. Intensive Care Med. 2007 Jan;33(1):137-42. doi: 10.1007/s00134-006-0422-0. Epub 2006 Nov 8. PubMed 17115135 ↗
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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
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Albert M, Williamson D, Muscedere J, Lauzier F, Rotstein C, Kanji S, Jiang X, Hall M, Heyland D. Candida in the respiratory tract secretions of critically ill patients and the impact of antifungal treatment: a randomized placebo controlled pilot trial (CANTREAT study). Intensive Care Med. 2014 Sep;40(9):1313-22. doi: 10.1007/s00134-014-3352-2. Epub 2014 Jul 1. PubMed 24981955 ↗
Williamson DR, Albert M, Perreault MM, Delisle MS, Muscedere J, Rotstein C, Jiang X, Heyland DK. The relationship between Candida species cultured from the respiratory tract and systemic inflammation in critically ill patients with ventilator-associated pneumonia. Can J Anaesth. 2011 Mar;58(3):275-84. doi: 10.1007/s12630-010-9439-5. Epub 2010 Dec 14. PubMed 21287306 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Feb 1, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00934934
Lead sponsor: Daren K. Heyland
Collaborators: The Physicians' Services Incorporated Foundation, Queen's University, Pfizer
Responsible party: Daren K. Heyland (Director, Clinical Evaluation Research Unit, Clinical Evaluation Research Unit at Kingston General Hospital) — Sponsor-investigator
First posted: Jul 8, 2009
Start date: Apr 2010
Primary completion: Aug 2012
Completion: Aug 2012
Results posted: Feb 1, 2021
Last update: Feb 1, 2021

Study contacts

Daren Heyland, MD

study chair · Clinical Evaluation Research Unit

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

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