Health TrialsbyHealthPanel

PTX3-targeted Antifungal Prophylaxis

ConditionsCandidiasisFungal InfectionAcute Myeloid LeukemiaGenetic PredispositionAspergillosis
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorBochud Pierre-Yves

About this trial

This is a prospective genetically-stratified randomized double-blind event-driven multicentre clinical trial to assess the efficacy of posaconazole-based antifungal prophylaxis allocation strategies for patients with acute myeloid leukemia who receive induction chemotherapy. Allocation strategy based on an invasive mold infection genetic risk will be double-blinded.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Signed Informed Consent according to national/local regulations.

Age ≥18 years.

Diagnosis of Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome in transformation (MDSit) treated with an intensive chemotherapy regimen, including induction / consolidation / salvage remission chemotherapy.

Planned hospital admission for the duration of the neutropenic phase (absolute neutrophils count <500 cells/mm3).

Disqualifiers

Patients with neutropenia (absolute neutrophils count<500 cells/mm3) upon presentation and prior to chemotherapy initiation.

Patients with a diagnosis of acute promyelocytic leukemia (APL) or AML-M3.

Patients with known history of allergy, hypersensitivity or serious reaction to azole antifungals

Women who are pregnant (positive blood/urine pregnancy test within 10 days before randomization) or breast-feeding.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Posaconazole

    Drug

    Posaconazole is a triazole with broad-spectrum activity, to include Candida species, Aspergillus species, and other fungal pathogens, including the Zygomycetes. Posaconazole is available as slow release tablets (300mg/day) and as intravenous (IV) formulation (300mg/day) and is licensed and approved in Switzerland for the prevention of IFI, including mold and yeast infections, in patients \>18 years who are at high risk of developing these types of infection (patients with long-term neutropenia or HCT recipients). Furthermore, international guidelines recommend posaconazole for primary antifungal prophylaxis in high-risk patients, such as AML patients with prolonged neutropenia. Posaconazole is available in Switzerland under the name of Noxafil® in capsules of 100mg, suspension of 40mg/mL and intravenous formulation of 300mg/16.7 mL.

  • Fluconazole

    Drug

    Fluconazole is an antifungal with activity against most Candida species. Fluconazole is licensed and approved in Switzerland for prophylaxis of IC in patients with neutropenia induced by chemotherapy or radiotherapy at a daily dose of 200 to 400 mg once daily. Fluconazole (200 mg or 400 mg once daily) is still currently used as primary antifungal prophylaxis (standard of care) in all 7 centers participating in this trial. Fluconazole is available in Switzerland under the name of Diflucan® in capsules of 50 mg, 150 mg and 200 mg and in powder for preparation of suspension (50 mg/5 ml and 200 mg/5 ml (forte)) or perfusion (2 mg/1 ml). Several generics of Diflucan® are authorized in Switzerland. Prescribing Diflucan® or any of its generics will remain at the discretion of and based on the standard operating procedures (SOP) at each institution.

Treatment groups

410 Participants
are divided into 2 treatment groups
Group A: high-risk PTX3 SNPsOther 2 interventions
Group B: low-risk PTX3 SNPsOther 2 interventions

Trial outcomes

Primary outcomes

1

Cumulative incidence of proven and probable invasive mold infection (IMI)

The cumulative incidence of proven and probable invasive mold infection (IMI) (based on published consensus guidelines by the EORTC/MSG groups and after validation by an independent adjudication committee of infectious disease experts blinded to treatment arms) in the intention-to-treat (ITT) population by day 180.

Time frame
Day 180

Secondary outcomes

1

Cumulative incidence of possible invasive mold infection (IMI)

The cumulative incidence of possible invasive mold infection (IMI) (based on published consensus guidelines by the EORTC/MSG groups and after validation by an independent adjudication committee of infectious disease experts blinded to treatment arms) by day 180 in the ITT population.

Time frame
Day 180
2

Cumulative incidence of probable and proven Invasive Fungal Infections (IFI)

The cumulative incidence of probable and proven Invasive Fungal Infections (IFI) (based on published consensus guidelines by the EORTC/MSG groups and after validation by an independent adjudication committee of infectious disease experts blinded to treatment arms), namely: (a) all IFI, (b) Invasive Aspergillosis (IA) only and (c) Invasive Candidiasis (IC) only in the ITT patient population by day 180.

Time frame
Day 180
3

Time to probable and proven invasive mold infection (IMI)

The time to probable and proven invasive mold infection (IMI) (based on published consensus guidelines by the EORTC/MSG groups and after validation by an independent adjudication committee of infectious disease experts blinded to treatment arms) during 180 days in the ITT population

Time frame
Day 180
4

Cumulative incidence of mortality

The cumulative incidence of mortality in the ITT population by day 180.

Time frame
Day 180

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Bochud Pierre-Yves

Lead sponsor

Centre Hospitalier Universitaire Vaudois

Sponsor institution

Swiss National Science Foundation

Collaborator

Source ClinicalTrials.gov
Apply now