Invasive aspergillosis MedDRA version: 20.1 Level: LLT Classification code 10022881 Term: Invasive bronchopulmonary aspergillosis System Organ Class: 100000004862
Conditions
Interventions
Trade Name: Ecalta
Product Name: anidulafungin
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: ANIDULAFUNGIN
CAS Number: 166663-25-8
Concentration unit: mg m
Sponsors
Erasmus MC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 18 years or older 2. Have started or will start voriconazole or isavuconazole (or posaconazole if voriconazole or isavuconazole cannot be given as per treating physician’s decision) as antifungal therapy on the baseline visit. 3. For all patients: presence of one of the EORTC/MSG host factors as defined in appendix 1 or being admitted to the ICU with influenza 4. For non-ICU patients or ICU patients without influenza: Meet the EORTC/MSG clinical criterium 5. For non-ICU patients or ICU patients without influenza: Meet the mycological criterium or fulfil inclusion criterium 7 6. For ICU patients with influenza we consider an isolated positive sputum culture for Aspergillus spp. insufficient as a mycological criterium. Therefore, in these patients only one of the following mycological criteria are acceptable; Serum galactomannan ?0.5, BAL galactomannan ?1.0 or Aspergillus spp. cultured in BAL fluid. 7. Please note that patients with AML receiving chemotherapy or patients with ALL receiving or having received corticosteroid therapy within the last 4 weeks in the context of their pre-phase, induction, consolidation, intensification or interphase treatment as well as patients receiving systemic immunosuppressive therapy for GVHD can be included before the mycological criterium is fulfilled on condition that they fulfill the EORTC/MSG lung CT radiology criteria (halo sign, well-described nodule, cavity as described in appendix 1) at the time of inclusion and as long as the mycological test results are expected to become available within 96 and no later than 7 days after inclusion. If these test results turn out to be negative, the patient will be withdrawn from the study and further treatment is at physician’s discretion. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 350 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 300
Exclusion criteria
Exclusion criteria: 1. Known history of allergy, hypersensitivity or serious reaction to azole or echinocandin antifungals; 2. Patients with chronic invasive aspergillosis or a chronic non-invasive aspergillus infection (e.g. aspergilloma) defined as the clinical or radiological sign of infection being present for >28 days. 3. Receipt of itraconazole, voriconazole, posaconazole or isavuconazole as prophylaxis for at least 7 days in the 14 days preceding the date of the first radiological signs of the Aspergillus infection. Patients in which the most recent serum level of the triazole given as prophylaxis was subtherapeutic can be included (*). 4. Receipt of echinocandin prophylaxis for >96 hours in the preceding 7 days 5. Receipt of systemic antifungal treatment with an echinocandin, an azole or amphotericin B for the current episode of invasive aspergillosis for a duration of > 96 hours. 6. For patients in the Netherlands only: Diagnostic testing to exclude azole resistance will not be possible (sputum cultures are negative and BAL sampling will not be performed) 7. ICU patients only: Patients with a sequential organ failure assessment (SOFA) score >11 at the time of screening for the study are excluded. If randomization is done >24 hours after screening the calculation should be repeated before the patient can be randomized (appendix 3) 8. ICU patients only: Patients in which weaning from the ventilator or ECMO system is deemed unlikely due to irreversible lung damage 9. Patients with any condition which, in the opinion of the investigator, could affect patient safety, preclude evaluation of response (e.g. because survival beyond 6 weeks is unlikely due to the underlying disease status) 10. Patient previously included in this study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate if the survival in patients with a triazole susceptible IA can be improved when the initial therapy consists of triazole and echinocandin combination therapy instead of triazole monotherapy.;Secondary Objective: 1. Evaluate if a triazole/echinocandin combination therapy improves the overall quality of life and if it is a cost-effective intervention 2. Evaluate the outcome of patients in which a triazole-resistant A. fumigatus is detected in relation to the initial antifungal therapy they had received (i.e. triazole monotherapy or combination therapy). 3. Evaluate the outcome of patients in which resistance testing is unsuccessful in function of the antifungal therapy they received. 4. Evaluate if the baseline serum galactomannan value and the serum galactomannan kinetics are predictive of overall 6-week mortality. ;Primary end point(s): Overall survival 42 days after the start of antifungal therapy in the MITT population;Timepoint(s) of evaluation of this end point: When the relevant data are available. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Overall aspergillus attributable mortality 12 weeks after the start of antifungal therapy(*). 2. Overall survival 12 weeks after the start of antifungal therapy in the MITT population 3. Overall survival 6 weeks after the start of therapy in the subgroup of patients in the MITT population with a positive serum galactomannan test at baseline. 4. Overall survival 6 weeks after the start of therapy in the subgroup of non-ICU patients who fulfill the EORTC/MSG probable or proven definition (MITT population). 5. Overall survival 6 weeks after the start of therapy in the subgroup of non-ICU patients with an underlying haematological disease (MITT population) 6. Overall survival 6 weeks after the start of therapy in the subgroup of non-ICU patients without an underlying haematological disease (MITT population) 7. Overall survival 6 weeks after the start of therapy in patients that started with triazole monotherapy and in which triazole resistance is detected during follow-up (MITT population) 8. Overall survival 6 weeks after the start of therapy in patients that started with triazole-anidulafungin combination therapy and in which triazole resistance is detected during follow-up (MITT population) 9. In the subgroup of patients with a positive serum galactomannan; Kinetics of serum galactomannan levels with combination versus monotherapy 10. Outcome of patients in which resistance testing was unsuccessful 11. Time to hospital discharge (in the MITT subgroup of patients admitted to the hospital at baseline) 12. Cost-effectivity of azole-anidulafungin combination therapy;Timepoint(s) of evaluation of this end point: When the relevant data are available. | — |
Countries
Belgium, Netherlands, Sweden
Contacts
Public ContactHOVON Data Centrum
Erasmus MC
Outcome results
None listed