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Effectiveness and Efficiency of a Voriconazole Preemptive Genotyping Strategy (VORIGENPHARM)

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ClinicalTrials.gov Identifier: NCT04238884
Recruitment Status : Recruiting
First Posted : January 23, 2020
Last Update Posted : January 23, 2020
Sponsor:
Information provided by (Responsible Party):
Instituto de Investigación Hospital Universitario La Paz

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.

Condition or disease Intervention/treatment Phase
Invasive Fungal Infections Drug: Voriconazole preemptive genotyping strategy Drug: Voriconazole clinical practice Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 146 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
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
Actual Study Start Date : January 2, 2020
Actual Primary Completion Date : January 18, 2020
Estimated Study Completion Date : December 31, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Experimental group
Based on the genetic study carried out and the patient's characteristics (age, weight, indication), the Pharmacogenetics Unit of the University Hospital La Paz will indicate the dose to be administered based on the therapeutic individualization protocol guided by pharmacogenetics.
Drug: Voriconazole preemptive genotyping strategy
The patients who finally receives voriconazole will be randomized to receive the dose according to a pharmacogenetic algorithm including CYP2C19 genotype and clinical and demographic information.

Active Comparator: Control group
No information will be provided and procedure will be carried out according to normal clinical practice, with clinical monitoring by the doctor in charge.
Drug: Voriconazole clinical practice
The patients who finally receives voriconazole will be randomized to receive the dose according to clinical practice




Primary Outcome Measures :
  1. Serum voriconazole concentration [ Time Frame: Day 5 of treatment ]
    Serum voriconazole concentration within the therapeutic range, in μg/mL.


Secondary Outcome Measures :
  1. Therapeutic failure [ Time Frame: Within 3 months ]

    % of patients with therapeutic failure. A patient has a therapeutic failure if:

    1. In patient with suspected or confirmed invasive aspergillosis: drug change or association, because of bad clinical or radiological evolution of the disease.
    2. In patient who receive prophylactic treatment: the necessity of change because of suspected or confirmed invasive fungal disease.

  2. Adverse event [ Time Frame: Within 3 months ]

    % of patients with a dose-dependent drug adverse event reaction.

    It will be considered dose-dependent drug adverse reactions:

    • Visual disturbances (photopsias)
    • Skin reactions
    • Neurotoxicity (confusion and visual hallucinations) and
    • Corrected QT interval (QTc) lengthening

  3. Costs by adverse event [ Time Frame: Day 90 of treatment ]
    Quantifying economic burden (in euros) associated with management of severe adverse events.

  4. Quality adjusted life years (QALY) [ Time Frame: Day 90 of treatment ]
    Measure of disease burden, including both the quality and the quantity of life lived.



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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04238884


Contacts
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Contact: Alberto M Borobia, MD, PhD +34-917277558 alberto.borobia@salud.madrid.org

Locations
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Spain
La Paz University Hospital Recruiting
Madrid, Spain, 28046
Contact: Alberto M Borobia, PI    +34917277558    alberto.borobia@salud.madrid.org   
Sponsors and Collaborators
Instituto de Investigación Hospital Universitario La Paz
Investigators
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Principal Investigator: Alberto M Borobia, MD, PhD La Paz University Hospital
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Instituto de Investigación Hospital Universitario La Paz
ClinicalTrials.gov Identifier: NCT04238884    
Other Study ID Numbers: 2019-000376-41
First Posted: January 23, 2020    Key Record Dates
Last Update Posted: January 23, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Mycoses
Invasive Fungal Infections
Bacterial Infections and Mycoses
Infections
Voriconazole
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP3A Inhibitors