Clinical trial NCT04238884: Effectiveness and Efficiency of a Voriconazole Preemptive Genotyping Strategy
Official title: Randomized and Multicenter Clinical Trial to Evaluate the Effectiveness and Efficiency of a Voriconazole Preemptive Genotyping Strategy in Patients With Risk of Aspergillosis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Invasive Fungal Infections
Lead sponsor: Instituto de Investigación Hospital Universitario La Paz
Sponsor class: OTHER
First posted: 2020-01-23
Enrollment: 146
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a phase IV pragmatic, multicentre, randomised, simple-blind, parallel arm, centre-stratified clinical trial. The main objective is to compare efficiency of voriconazole preemptive genotyping strategy, compared with routine practice.

Detailed description: Primary outcome is serum level of voriconazole on fifth day. Secondary outcome is a combined variable of therapeutic failure and adverse events, associated with voriconazole. A total of 146 patients with risk of undergoing invasive aspergillosis who potentially will receive voriconazole will be recruited, and CYP2C19 will be genotyped. If the patient receives voriconazole finally, he will be randomized (1:1 experimental/control). In the experimental arm patients receive dose according to pharmacogenetic algorithm including CYP2C19 genotype and clinical and demographic information. In the control arm patients receive dose according to clinical practice guidelines. In addition, a Spain national health system (NHS) point-of-view cost-effectiveness evaluation is going to be done. Direct costs calculation of each arm will be done.

Eligibility criteria: Inclusion Criteria:

1. Patient at risk of developing invasive aspergillosis, that will potentially receive treatment or prophylaxis with voriconazole:

   A. Pediatric population: children who are going to receive a transplant of hematopoietic precursors (HSCT) and acute myeloid leukemias, as well as relapses of it.

   B. Adult population: patients diagnosed with acute leukemia, and those patients with expected prolonged neutropenia, secondary to hematological process and / or after specific treatment (aplastic anemia and variants, myelodysplastic syndrome, solid organ or bone marrow transplant, etc.), and those whose responsible clinician consider individually that they could present a risk of developing a fungal infection.
2. Those who agree to participate in the study by signing informed consent (patients equal or over 18 years old)
3. Subjects under 18 years old whose representative / legal guardian has voluntarily signed the informed consent.
4. In the case of mature under 18 years subjects (12-17 years of age), in addition to the consent signed by the legal guardian, the consent of the subject will be obtained.

Exclusion Criteria:

1. Patients who for any reason should not be included in the study according to the criteria of the research team.
2. Subjects who are not capable to understand the information sheet and unable to sign the informed consent.

Primary outcomes:
measure: Serum voriconazole concentration
timeFrame: Day 5 of treatment
Secondary outcomes:
measure: Therapeutic failure
timeFrame: Within 3 months
measure: Adverse event
timeFrame: Within 3 months
measure: Costs by adverse event
timeFrame: Day 90 of treatment
measure: Quality adjusted life years (QALY)
timeFrame: Day 90 of treatment
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: La Paz University Hospital
Study officials:
affiliation: La Paz University Hospital
name: Alberto M Borobia, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Monserrat Villatoro J, Garcia Garcia I, Bueno D, de la Camara R, Estebanez M, Lopez de la Guia A, Abad-Santos F, Anton C, Mejia G, Otero MJ, Ramirez Garcia E, Frias Iniesta J, Carcas A, Borobia AM. Randomised multicentre clinical trial to evaluate voriconazole pre-emptive genotyping strategy in patients with risk of aspergillosis: vorigenipharm study protocol. BMJ Open. 2020 Oct 1;10(10):e037443. doi: 10.1136/bmjopen-2020-037443.