Invasive Candidiasis
Conditions
Keywords
Candida, Prophylaxis, High risk adults, Intensive care unit (ICU)
Brief summary
Adults admitted to intensive care units are at risk for a variety of complications. Infections due to the fungus called candida are of particular concern. The study will test the possibility that caspofungin, a new therapy for fungal infections, can successfully reduce the rate of candida infections in subjects at risk. It will also test if caspofungin is useful in treating subjects for this disease when diagnosed using a new blood test that is performed twice weekly, permitting earlier diagnosis than current practice standards.
Interventions
DRUGCaspofungin
50 mg IV daily
DRUGNormal Saline
100 cc IV daily
Sponsors
Merck Sharp & Dohme LLC
Mycoses Study Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Non-pregnant \>18 yrs of age * Subjects admitted to ICU during the preceding 3 days and expected to stay in the ICU for at least another 48 hours.Subjects can be enrolled on days 3-5 of ICU admission. * Subjects meeting the clinical prediction rule
Exclusion criteria
* Subjects with an allergy/intolerance to caspofungin or echinocandin analog * absolute neutrophil count \<500/mm3 at study entry or likely to develop such a count during therapy * acquired immunodeficiency syndrome, aplastic anemia or chronic granulomatous disease * moderate or severe hepatic insufficiency * subjects who are pregnant or lactating * unlikely to survive \< 24 hours * subjects who have received systemic antifungal therapy within 10 days prior to study entry * Documented active proven or probable invasive fungal infection upon enrollment * previously enrolled in this study * Currently on another investigational agent or have received an investigational agent within 10 days prior to study entry.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proven and Probable Invasive Candidiasis Based on Modified Mycoses Study Group/European Organization for Research and Treatment of Cancer (MSG/EORTC) Criteria. | Within 7 days after end of therapy | Modified MSG/EORTC criteria for the diagnosis of fungal infections: Proven invasive candidiasis is defined as candidemia, Candida cultured from a sterile site, or histopathological evidence of candida infection. Probable invasive candidiasis is defined as 2 consecutive positive beta glucan levels in the presence of signs and symptoms of infection. |
Secondary
| Measure | Time frame |
|---|---|
| All Cause Mortality | Within 7 days of end of therapy |
| Initiation of Other Antifungals | Within 7 days after end of therapy |
| Time to Development of Proven or Probable Invasive Candidiasis | Within 7 days after end of therapy |
| Incidence of Proven and Probable Invasive Fungal Infections Other Than Invasive Candidiasis. | Within 7 days after end of therapy |
| Incidence of Proven Invasive Candidiasis by MSG/ EORTC Criteria. | Within 7 days of end of therapy |
| Incidence of Complete and Partial Response by Clinical and Microbiological or Serological Evidence for Subjects on the Pre-emptive Therapy Phase. | Within 14 days after end of therapy |
| Hospital Metrics (to be Evaluated Separately for Prophylaxis and Pre-emptive Therapy Phases); Length of Stay in the Hospital, Length of Stay in the ICU, and the Costs Data for the ICU Stay and the Hospitalization, if Available. | Hospital discharge |
| Subjects Who Discontinue Study Therapy Due to a Drug-related Adverse Event | Up to 14 days after end of therapy |
| Subjects With 1 or More Serious Drug-related Adverse Event(s) | Up to 14 days after end of therapy |
| Time to Beta Glucan Negativity in Pre-emptive Phase. | Within 14 days after end of therapy |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Prophylaxis Caspofungin 50 mg IV daily up to 28 days of therapy | 117 |
| Placebo Normal Saline 100 cc IV daily | 102 |
| Total | 219 |
Baseline characteristics
| Characteristic | Total | Placebo | Prophylaxis |
|---|---|---|---|
| Acute Physiology And Chronic Health Evaluation (APACHE) II score (minimum 0, maximum 71) | 25.2 Score on a scale STANDARD_DEVIATION 8.3 | 25.1 Score on a scale STANDARD_DEVIATION 8.7 | 25.3 Score on a scale STANDARD_DEVIATION 8 |
| Age Continuous | 57.5 years STANDARD_DEVIATION 17.1 | 56.7 years STANDARD_DEVIATION 16.6 | 58.2 years STANDARD_DEVIATION 17.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 15 Participants | 8 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 203 Participants | 94 Participants | 109 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 70 Participants | 35 Participants | 35 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 8 Participants | 5 Participants | 3 Participants |
| Race (NIH/OMB) White | 138 Participants | 60 Participants | 78 Participants |
| Sex: Female, Male Female | 87 Participants | 41 Participants | 46 Participants |
| Sex: Female, Male Male | 132 Participants | 61 Participants | 71 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 106 / 117 | 87 / 102 |
| serious Total, serious adverse events | 33 / 117 | 28 / 102 |
Outcome results
Primary
Proven and Probable Invasive Candidiasis Based on Modified Mycoses Study Group/European Organization for Research and Treatment of Cancer (MSG/EORTC) Criteria.
Modified MSG/EORTC criteria for the diagnosis of fungal infections: Proven invasive candidiasis is defined as candidemia, Candida cultured from a sterile site, or histopathological evidence of candida infection. Probable invasive candidiasis is defined as 2 consecutive positive beta glucan levels in the presence of signs and symptoms of infection.
Time frame: Within 7 days after end of therapy
Population: Modified intent-to-treat population, defined as subjects who received at least one dose of study drug and did not have baseline invasive candidiasis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prophylaxis | Proven and Probable Invasive Candidiasis Based on Modified Mycoses Study Group/European Organization for Research and Treatment of Cancer (MSG/EORTC) Criteria. | 9.8 percent of participants |
| Placebo | Proven and Probable Invasive Candidiasis Based on Modified Mycoses Study Group/European Organization for Research and Treatment of Cancer (MSG/EORTC) Criteria. | 16.6 percent of participants |
p-value: 0.14Cochran-Mantel-Haenszel
Secondary
All Cause Mortality
Time frame: Within 7 days of end of therapy
Secondary
Hospital Metrics (to be Evaluated Separately for Prophylaxis and Pre-emptive Therapy Phases); Length of Stay in the Hospital, Length of Stay in the ICU, and the Costs Data for the ICU Stay and the Hospitalization, if Available.
Time frame: Hospital discharge
Secondary
Incidence of Complete and Partial Response by Clinical and Microbiological or Serological Evidence for Subjects on the Pre-emptive Therapy Phase.
Time frame: Within 14 days after end of therapy
Secondary
Incidence of Proven and Probable Invasive Fungal Infections Other Than Invasive Candidiasis.
Time frame: Within 7 days after end of therapy
Secondary
Incidence of Proven Invasive Candidiasis by MSG/ EORTC Criteria.
Time frame: Within 7 days of end of therapy
Secondary
Initiation of Other Antifungals
Time frame: Within 7 days after end of therapy
Secondary
Subjects Who Discontinue Study Therapy Due to a Drug-related Adverse Event
Time frame: Up to 14 days after end of therapy
Population: Safety population, defined as all subjects who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prophylaxis | Subjects Who Discontinue Study Therapy Due to a Drug-related Adverse Event | 2 participants |
| Placebo | Subjects Who Discontinue Study Therapy Due to a Drug-related Adverse Event | 2 participants |
Secondary
Subjects With 1 or More Serious Drug-related Adverse Event(s)
Time frame: Up to 14 days after end of therapy
Population: Safety population, defined as all subjects who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prophylaxis | Subjects With 1 or More Serious Drug-related Adverse Event(s) | 1 participants |
| Placebo | Subjects With 1 or More Serious Drug-related Adverse Event(s) | 0 participants |
Secondary
Time to Beta Glucan Negativity in Pre-emptive Phase.
Time frame: Within 14 days after end of therapy
Secondary
Time to Development of Proven or Probable Invasive Candidiasis
Time frame: Within 7 days after end of therapy