Erasmus MC HO502 Other

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Main info

Identificatie:
HO502 (DUET)
Sponsor:
Erasmus MC
Working group party:
SCT & Supportive care
Stadium:
1st lijn
Echelon:
Limited Site Selection
Included patients:
4
(of 650)
Active sites:
2
(of 28)
16 sites are pending
Title:

Azole-echinocandin combination therapy for invasive aspergillosis. A multicenter pragmatic randomized superiority trial

Timeline

Scheduled
Actual
2020
27 jan.
Opportunity
2020
01 nov.
EC Approval
2020
03 dec.
Submission in Progress
2020
28 dec.
EC Approval
2021
19 apr.
First Site
2021
01 mei
FPI
2021
07 mei
Activated
2021
12 mei
First Site

Flow

Flow

Details

Phase:
Prospective randomized Phase III study
Monitoring Type:
Site Evaluation Visit
Objectives:

Primary objective
1. 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 objectives
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 survival.

Eligibility

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 (protocol) or being admitted to the ICU with influenza
4. For non-ICU patients or ICU patients without influenza: Meet the EORTC/MSG clinical criterium (appendix 1, protocol)
5. For non-ICU patients or ICU patients without influenza: Meet the mycological criterium (appendix 1, protocol) or fulfil inclusion criterium 7
6. For ICU patients with influenza we consider an isolated positive sputum culture for Aspergillus spp. insufficient as amycological 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.
8. Written informed consent by patient or legal representative.

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 or an azole 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, protocol)
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

(*) Subtherapeutic levels are defined as itraconazole (parent compound only) <0.5 mg/L or posaconazole <0.7mg/L or voriconazole <1.0mg/L or isavuconazole <1.0mg/L

Registration Details

Eligible patients should be randomized before start of study treatment. Patients need to be registered and randomized at the HOVON Data Center by one of the following options:

  • By ALEA; Use goto eCRF button > select the [Patient tab] and click the [Add new patient] button. Complete all items and click the [Submit] button
  • By mailing the completed registration/randomization CRF to hdc@erasmusmc.nl
  • By phone +31 (0)10 704 1560 Monday through Friday, from 09:00 to 17:00 CET

The following information will be requested at registration:

Protocol number
Institution name
Name of caller/responsible investigator
Sex
(Partial) date of birth and age at time of registration
Date written informed consent
Specific items patient gives consent for (see ICF)
Eligibility criteria

Participating Sites

Ziekenhuizen die deelnemen aan het onderzoek staan benoemd op de HOVON website bij het onderzoek. Het kan zijn dat uw ziekenhuis niet genoemd wordt, maar wel aan het onderzoek deelneemt. Informeer hiernaar bij uw arts.

Site
18 results
Order by
Accrual rate
Activation date
NL-Rotterdam-ERASMUSMC
4
12 mei 2021
BE-Brugge-AZBRUGGE
BE-Brussel-BORDET
BE-Liege-CHULIEGE
NL-Leeuwarden-MCL
NL-Groningen-UMCG
NL-Nieuwegein-ANTONIUS
NL-Nijmegen-RADBOUDUMC
NL-Amsterdam-OLVG
NL-Amersfoort-MEANDERMC
NL-Eindhoven-MAXIMAMC
NL-Maastricht-MUMC
NL-Amsterdam-AMC
BE-Gent-UZGENT
BE-Leuven-UZLEUVEN
02 jul. 2021
BE-Antwerpen Edegem-UZA
BE-Bruxelles-STLUC
BE-Brussel-ERASME
= Active hospitals
= Inactive hospitals

Participating Parties

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