Invasive Candidiasis
Conditions
Brief summary
Comparison of the safety and effectiveness of standard drug dosing versus a daily dose 3 times higher than the standard dose in patients with invasive candidiasis (bloodstream and/or systemic yeast infections)
Interventions
Caspofungin acetate 50 mg IV infusion (diluted with 9% saline) (following a 70-mg IV loading dose on Day 1); Caspofungin acetate 150 mg IV infusion (diluted with 9% saline) administered daily, over the course of \ 2 hrs. Duration of Treatment - 14-90 days.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Clinical and Laboratory evidence of blood stream &/or systemic candida infections
Exclusion criteria
* Possible candida contamination * Candida colonization (non invasive infection), urine, cardiac, bone or brain and prosthetic device infections * Acute or moderately severe liver disease * Abnormal liver function tests * Abnormal blood clotting for patients on blood thinners
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Who Develop Significant Drug-related Adverse Events. | 90 Days | Number of patients with at least 1 significant drug-related adverse event (serious drug-related or drug-related adverse events leading to caspofungin discontinuation) while on caspofungin study therapy or during the immediate 14-day post-caspofungin therapy period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With a Favorable Overall Response. | 90 Days | Number of patients with a favorable overall response, defined as a clinical response of cure or apparent cure along with a microbiological response of eradication or presumptive eradication at the End of Caspofungin Therapy. |
Participant flow
Recruitment details
This was a Phase III study. The first patient was enrolled (FPE) on 13-Jan-2006. The last patient's last visit (LPLV) was on 13-Mar-2008. A total of 38 inpatient centers were involved in the recruitment worldwide (14 in the United States, 13 in the European Union, 7 in Central or South America, and 4 in Asia)
Participants by arm
| Arm | Count |
|---|---|
| Caspofungin 70/50 mg Caspofungin 50 mg IV daily (following a 70-mg IV loading dose on Day 1) | 104 |
| Caspofungin 150 mg Caspofungin 150 mg IV daily | 100 |
| Total | 204 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 25 | 29 |
| Overall Study | Lack of Efficacy | 2 | 1 |
| Overall Study | Lost to Follow-up | 6 | 5 |
| Overall Study | Patient Moved | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 3 |
| Overall Study | Pt died out of posttherapy report period | 6 | 5 |
| Overall Study | Pt was considered untreatable | 0 | 1 |
| Overall Study | Withdrawal by Subject | 6 | 2 |
Baseline characteristics
| Characteristic | Total | Caspofungin 70/50 mg | Caspofungin 150 mg |
|---|---|---|---|
| Age, Continuous | 56.9 years | 56.0 years | 57.8 years |
| APACHE II Score (at Study Entry) | 16.8 Units on a Scale | 16.5 Units on a Scale | 17.0 Units on a Scale |
| Race/Ethnicity, Customized Asian | 33 participants | 17 participants | 16 participants |
| Race/Ethnicity, Customized Black | 23 participants | 11 participants | 12 participants |
| Race/Ethnicity, Customized Caucasian | 135 participants | 70 participants | 65 participants |
| Race/Ethnicity, Customized Hispanic | 9 participants | 4 participants | 5 participants |
| Race/Ethnicity, Customized Other | 4 participants | 2 participants | 2 participants |
| Sex: Female, Male Female | 90 Participants | 50 Participants | 40 Participants |
| Sex: Female, Male Male | 114 Participants | 54 Participants | 60 Participants |
| Site Of Invasive Candida Infection Abscess(involving an intra-abdominal site) | 2 Participants | 0 Participants | 2 Participants |
| Site Of Invasive Candida Infection Abscess (involving a non-abdominal site) | 1 Participants | 0 Participants | 1 Participants |
| Site Of Invasive Candida Infection Acute disseminated candidiasis or multiple sites | 13 Participants | 6 Participants | 7 Participants |
| Site Of Invasive Candida Infection Blood (candidemia) | 172 Participants | 91 Participants | 81 Participants |
| Site Of Invasive Candida Infection Chronic disseminated candidiasis (hepatosplenic) | 1 Participants | 1 Participants | 0 Participants |
| Site Of Invasive Candida Infection Fungemia (non Candida) | 2 Participants | 0 Participants | 2 Participants |
| Site Of Invasive Candida Infection Kidney (Pyelonephritis) | 1 Participants | 0 Participants | 1 Participants |
| Site Of Invasive Candida Infection Lung (Pneumonia) | 2 Participants | 1 Participants | 1 Participants |
| Site Of Invasive Candida Infection Peritoneal fluid (Peritonitis) | 9 Participants | 4 Participants | 5 Participants |
| Site Of Invasive Candida Infection Pleural fluid (Empyema) | 1 Participants | 1 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 69 / — | 70 / — |
| serious Total, serious adverse events | 46 / — | 44 / — |
Outcome results
Primary
Number of Patients Who Develop Significant Drug-related Adverse Events.
Number of patients with at least 1 significant drug-related adverse event (serious drug-related or drug-related adverse events leading to caspofungin discontinuation) while on caspofungin study therapy or during the immediate 14-day post-caspofungin therapy period.
Time frame: 90 Days
Population: All patients as treated population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Caspofungin 70/50 mg | Number of Patients Who Develop Significant Drug-related Adverse Events. | 2 Participants |
| Caspofungin 150 mg | Number of Patients Who Develop Significant Drug-related Adverse Events. | 3 Participants |
Comparison: A significant drug-related adverse event was defined as either a drug-related serious adverse event or a drug-related adverse event leading to discontinuation of caspofungin therapy. Comparison between the 2 caspofungin groups was based on upper bound of the 95% confidence interval for the difference.95% CI: [-4.1, 6.8]
Secondary
Number of Patients With a Favorable Overall Response.
Number of patients with a favorable overall response, defined as a clinical response of cure or apparent cure along with a microbiological response of eradication or presumptive eradication at the End of Caspofungin Therapy.
Time frame: 90 Days
Population: Full Analysis Set (FAS): Included those patients who received at least 1 full dose of caspofungin study therapy and had a documented diagnosis of invasive candidiasis from a sterile, invasive body site, as defined in the protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Caspofungin 70/50 mg | Number of Patients With a Favorable Overall Response. | 73 Participants |
| Caspofungin 150 mg | Number of Patients With a Favorable Overall Response. | 74 Participants |
Comparison: There was no formal hypothesis testing for efficacy in this study. The main efficacy analysis was the number (percentage) of patients with a favorable overall response at the end of caspofungin study therapy, together with the within treatment 95% exact binomial confidence intervals, and the estimated treatment difference, and its 95% confidence interval.95% CI: [-5.9, 18.4]