Invasive Fungal Infections
Conditions
Keywords
observational study, voriconazole, high-risk patients
Brief summary
Assessment of safety and efficacy of voriconazole in real-life setting in the treatment of high risk patients with invasive fungal infections. The study is conducted in Slovakia only.
Interventions
DRUGvoriconazole (VFEND®)
The use and dosage recommendations for voriconazole (VFEND®) will take place on the basis of the Summary of Product Characteristics (SmPC) and will be adjusted solely according to medical and therapeutic necessity. The formulation and dose will be managed by the treating physician according to the SmPC, disease and clinical situation. According to the SmPC, in the adults the treatment should be started with the loading dose of 6 mg/kg of voriconazole iv. every 12 hours (during the first 24 hrs) followed by the maintenance dose of 4 mg/kg BID. For peroral formulations, the initial dose should be depending on the weight of the patient 400 mg or 200 mg BID during the first 24 hrs, followed by the maintenance dose of 200 mg or 100 mg of voriconazole BID respectively For paediatric population (\<12 years of age), there is no initial dose necessary. Depending on the formulation, the daily dosage should be in children 7 mg/kg iv. BID or 200 mg of voriconazole orally BID.
Sponsors
Pfizer
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
2 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female patient of age 2 years or older. * High-risk patients with proven, probable or possible invasive fungal infection (IFI) according to the EORTC/MSG criteria. * Patients indicated for secondary prophylaxis of invasive aspergillosis.
Exclusion criteria
* Patients with known hypersensitivity to voriconazole or to any of the excipients. * Patients with contraindicated concomitant medications according to the SmPC. * Children less than 2 years of age. * Pregnancy and lactation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinical and/or Mycological Efficacy by Response at the End of Treatment (EOT) Visit | up to 2 weeks (EOT visit) | Clinical, mycological responses: clinical cure, clinical improvement, no clinical cure, mycological cure, no mycological cure, and no mycological culture performed. Participants could have had more than one response. Responses were based on the investigator's judgement according to the Infectious Disease Society of America, European Conference on Infections in Leukemia, and European Committee on Antimicrobial Susceptibility Testing guidelines. |
| Number of Participants With Clinical and/or Mycological Efficacy by Response at the Test-of-Cure Visit | more than 2 weeks (Test-of-Cure visit) | Clinical, mycological responses: clinical cure, clinical improvement, no clinical cure, mycological cure, no mycological cure, no mycological culture performed, death, and lost from follow-up. Participants could have had more than one response. Responses were based on the investigator's judgement according to the Infectious Disease Society of America, European Conference on Infections in Leukemia, and European Committee on Antimicrobial Susceptibility Testing guidelines. |
| Number of Participants With Investigator's Satisfaction With the Efficacy of Voriconazole Assessment at the EOT Visit | up to 2 weeks (EOT visit) | Investigator's Satisfaction Responses: very good, good, moderate, poor. Responses were based on the investigator's judgement. |
| Number of Participants With Investigator's Satisfaction With the Tolerability of Voriconazole Assessment at the EOT Visit | up to 2 weeks (EOT visit) | Investigator's Satisfaction Responses: very good, good, moderate, poor. Responses were based on the investigator's judgement. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Voriconazole In adults, treatment was started with the loading dose of 6 mg/kg of voriconazole intravenously every 12 hours (during the first 24 hrs) followed by the maintenance dose of 4 mg/kg twice a day (BID). Adults with a weight of \>40 kg receiving the oral formulation received a loading dose of 400 mg BID during the first 24 hours, followed by a maintenance dose of 200 mg BID for the duration of the study.
Adults with a weight of \<40 kg receiving the oral formulation received a loading dose of 200 mg BID during the first 24 hours, followed by a maintenance dose of 100 mg BID for the duration of the study. Pediatric participants under 12 years of age received 7 mg/kg IV BID or 200 mg orally BID for the duration of the study. A loading dose was not required in participants under 12 years of age. | 177 |
| Total | 177 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Death | 30 |
| Overall Study | Lack of Efficacy | 13 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Other | 7 |
Baseline characteristics
| Characteristic | Voriconazole |
|---|---|
| Age, Customized 19 to 44 years | 52 participants |
| Age, Customized 2 to 18 years | 16 participants |
| Age, Customized < 2 years | 3 participants |
| Age, Customized 45 to 64 years | 80 participants |
| Age, Customized > = 65 years | 26 participants |
| Number of Participants Having Certain Methods of Diagnosis of Invasive Aspergillosis Biopsy | 2 participants |
| Number of Participants Having Certain Methods of Diagnosis of Invasive Aspergillosis Blood Culture | 8 participants |
| Number of Participants Having Certain Methods of Diagnosis of Invasive Aspergillosis Bronchoalveolar Lavage (BAL) | 23 participants |
| Number of Participants Having Certain Methods of Diagnosis of Invasive Aspergillosis Galactomannan | 55 participants |
| Number of Participants Having Certain Methods of Diagnosis of Invasive Aspergillosis Hi-Resolution Computed Tomography | 91 participants |
| Number of Participants Having Certain Methods of Diagnosis of Invasive Aspergillosis Polymerase Chain Reaction (PCR) | 5 participants |
| Number of Participants with Risk Factors of Invasive Fungal Infections Allogenic Bone Marrow Transplant | 13 participants |
| Number of Participants with Risk Factors of Invasive Fungal Infections Antibiotic Prophylaxis | 81 participants |
| Number of Participants with Risk Factors of Invasive Fungal Infections Antifungal Prophylaxis | 114 participants |
| Number of Participants with Risk Factors of Invasive Fungal Infections Autologic Bone Marrow Transplant | 11 participants |
| Number of Participants with Risk Factors of Invasive Fungal Infections Central Venous Catether | 110 participants |
| Number of Participants with Risk Factors of Invasive Fungal Infections Chemotherapy | 122 participants |
| Number of Participants with Risk Factors of Invasive Fungal Infections Cytomegalovirus Infection | 13 participants |
| Number of Participants with Risk Factors of Invasive Fungal Infections Diabetes Mellitus | 10 participants |
| Number of Participants with Risk Factors of Invasive Fungal Infections Graft-Versus-Host Disease | 7 participants |
| Number of Participants with Risk Factors of Invasive Fungal Infections Hemodialysis | 5 participants |
| Number of Participants with Risk Factors of Invasive Fungal Infections Immunosuppressive Treatment | 42 participants |
| Number of Participants with Risk Factors of Invasive Fungal Infections Malignant Tumour | 110 participants |
| Number of Participants with Risk Factors of Invasive Fungal Infections Mucositisis | 38 participants |
| Number of Participants with Risk Factors of Invasive Fungal Infections Neuropenia | 104 participants |
| Number of Participants with Risk Factors of Invasive Fungal Infections Organ Transplant | 3 participants |
| Number of Participants with Risk Factors of Invasive Fungal Infections Other Invasive Mycosis | 5 participants |
| Number of Participants with Risk Factors of Invasive Fungal Infections Polytrauma | 13 participants |
| Number of Participants with Risk Factors of Invasive Fungal Infections Previous Antibiotic Treatment | 120 participants |
| Number of Participants with Risk Factors of Invasive Fungal Infections Primary/Secondary Immunodeficiency | 101 participants |
| Number of Participants with Risk Factors of Invasive Fungal Infections Radiotherapy | 8 participants |
| Number of Participants with Risk Factors of Invasive Fungal Infections Steroid Treatment | 74 participants |
| Number of Participants with Risk Factors of Invasive Fungal Infections Total Parental Nutrition | 35 participants |
| Number of Participants with Risk Factors of Invasive Fungal Infections Undergone Surgery | 23 participants |
| Number of Participants with Risk Factors of Invasive Fungal Infections Ventilation (Intubation) | 32 participants |
| Sex: Female, Male Female | 73 Participants |
| Sex: Female, Male Male | 104 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 6 / 177 |
| serious Total, serious adverse events | 34 / 177 |
Outcome results
Primary
Number of Participants With Clinical and/or Mycological Efficacy by Response at the End of Treatment (EOT) Visit
Clinical, mycological responses: clinical cure, clinical improvement, no clinical cure, mycological cure, no mycological cure, and no mycological culture performed. Participants could have had more than one response. Responses were based on the investigator's judgement according to the Infectious Disease Society of America, European Conference on Infections in Leukemia, and European Committee on Antimicrobial Susceptibility Testing guidelines.
Time frame: up to 2 weeks (EOT visit)
Population: Full Analysis Set (FAS) = all enrolled participants who were administered the study medication and had post baseline documentation of efficacy available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Voriconazole | Number of Participants With Clinical and/or Mycological Efficacy by Response at the End of Treatment (EOT) Visit | Clinical Improvement | 64 participants |
| Voriconazole | Number of Participants With Clinical and/or Mycological Efficacy by Response at the End of Treatment (EOT) Visit | Clinical Cure | 64 participants |
| Voriconazole | Number of Participants With Clinical and/or Mycological Efficacy by Response at the End of Treatment (EOT) Visit | No Clinical Cure | 36 participants |
| Voriconazole | Number of Participants With Clinical and/or Mycological Efficacy by Response at the End of Treatment (EOT) Visit | Mycological Cure | 34 participants |
| Voriconazole | Number of Participants With Clinical and/or Mycological Efficacy by Response at the End of Treatment (EOT) Visit | No Mycological Cure | 10 participants |
| Voriconazole | Number of Participants With Clinical and/or Mycological Efficacy by Response at the End of Treatment (EOT) Visit | No Mycological Culture Performed | 40 participants |
Primary
Number of Participants With Clinical and/or Mycological Efficacy by Response at the Test-of-Cure Visit
Clinical, mycological responses: clinical cure, clinical improvement, no clinical cure, mycological cure, no mycological cure, no mycological culture performed, death, and lost from follow-up. Participants could have had more than one response. Responses were based on the investigator's judgement according to the Infectious Disease Society of America, European Conference on Infections in Leukemia, and European Committee on Antimicrobial Susceptibility Testing guidelines.
Time frame: more than 2 weeks (Test-of-Cure visit)
Population: FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Voriconazole | Number of Participants With Clinical and/or Mycological Efficacy by Response at the Test-of-Cure Visit | Clinical Cure | 54 participants |
| Voriconazole | Number of Participants With Clinical and/or Mycological Efficacy by Response at the Test-of-Cure Visit | Clinical Improvement | 46 participants |
| Voriconazole | Number of Participants With Clinical and/or Mycological Efficacy by Response at the Test-of-Cure Visit | No Clinical Cure | 7 participants |
| Voriconazole | Number of Participants With Clinical and/or Mycological Efficacy by Response at the Test-of-Cure Visit | Mycological Cure | 31 participants |
| Voriconazole | Number of Participants With Clinical and/or Mycological Efficacy by Response at the Test-of-Cure Visit | No Mycological Cure | 1 participants |
| Voriconazole | Number of Participants With Clinical and/or Mycological Efficacy by Response at the Test-of-Cure Visit | No Mycological Culture Performed | 19 participants |
| Voriconazole | Number of Participants With Clinical and/or Mycological Efficacy by Response at the Test-of-Cure Visit | Death | 41 participants |
| Voriconazole | Number of Participants With Clinical and/or Mycological Efficacy by Response at the Test-of-Cure Visit | Lost From Follow-Up | 11 participants |
Primary
Number of Participants With Investigator's Satisfaction With the Efficacy of Voriconazole Assessment at the EOT Visit
Investigator's Satisfaction Responses: very good, good, moderate, poor. Responses were based on the investigator's judgement.
Time frame: up to 2 weeks (EOT visit)
Population: FAS. Number or participants analyzed = Number of participants with Investigator's satisfaction response for the efficacy of voriconazole at the EOT Visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Voriconazole | Number of Participants With Investigator's Satisfaction With the Efficacy of Voriconazole Assessment at the EOT Visit | Very Good | 85 participants |
| Voriconazole | Number of Participants With Investigator's Satisfaction With the Efficacy of Voriconazole Assessment at the EOT Visit | Good | 49 participants |
| Voriconazole | Number of Participants With Investigator's Satisfaction With the Efficacy of Voriconazole Assessment at the EOT Visit | Moderate | 33 participants |
| Voriconazole | Number of Participants With Investigator's Satisfaction With the Efficacy of Voriconazole Assessment at the EOT Visit | Poor | 5 participants |
Primary
Number of Participants With Investigator's Satisfaction With the Tolerability of Voriconazole Assessment at the EOT Visit
Investigator's Satisfaction Responses: very good, good, moderate, poor. Responses were based on the investigator's judgement.
Time frame: up to 2 weeks (EOT visit)
Population: FAS. Number or participants analyzed = Number of participants with Investigator's satisfaction response for the tolerability of voriconazole at the EOT Visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Voriconazole | Number of Participants With Investigator's Satisfaction With the Tolerability of Voriconazole Assessment at the EOT Visit | Very Good | 105 participants |
| Voriconazole | Number of Participants With Investigator's Satisfaction With the Tolerability of Voriconazole Assessment at the EOT Visit | Good | 61 participants |
| Voriconazole | Number of Participants With Investigator's Satisfaction With the Tolerability of Voriconazole Assessment at the EOT Visit | Moderate | 8 participants |
| Voriconazole | Number of Participants With Investigator's Satisfaction With the Tolerability of Voriconazole Assessment at the EOT Visit | Poor | 0 participants |