Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
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

Tracking Information
First Submitted Date  ICMJE January 18, 2020
First Posted Date  ICMJE January 23, 2020
Last Update Posted Date January 23, 2020
Actual Study Start Date  ICMJE January 2, 2020
Actual Primary Completion Date January 18, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 22, 2020)
Serum voriconazole concentration [ Time Frame: Day 5 of treatment ]
Serum voriconazole concentration within the therapeutic range, in μg/mL.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: January 22, 2020)
  • 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.
  • 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
  • Costs by adverse event [ Time Frame: Day 90 of treatment ]
    Quantifying economic burden (in euros) associated with management of severe adverse events.
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effectiveness and Efficiency of a Voriconazole Preemptive Genotyping Strategy
Official Title  ICMJE Randomized and Multicenter Clinical Trial to Evaluate the Effectiveness and Efficiency of a Voriconazole Preemptive Genotyping Strategy in Patients With Risk of Aspergillosis
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Condition  ICMJE Invasive Fungal Infections
Intervention  ICMJE
  • 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.
  • Drug: Voriconazole clinical practice
    The patients who finally receives voriconazole will be randomized to receive the dose according to clinical practice
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Voriconazole preemptive genotyping strategy
  • 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.
    Intervention: Drug: Voriconazole clinical practice
Publications * Monserrat Villatoro J, García García I, Bueno D, de la Cámara R, Estébanez M, López de la Guía A, Abad-Santos F, Antón C, Mejía G, Otero MJ, Ramírez García E, Frías 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 22, 2020)
146
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2022
Actual Primary Completion Date January 18, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Alberto M Borobia, MD, PhD +34-917277558 alberto.borobia@salud.madrid.org
Listed Location Countries  ICMJE Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04238884
Other Study ID Numbers  ICMJE 2019-000376-41
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Instituto de Investigación Hospital Universitario La Paz
Study Sponsor  ICMJE Instituto de Investigación Hospital Universitario La Paz
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Alberto M Borobia, MD, PhD La Paz University Hospital
PRS Account Instituto de Investigación Hospital Universitario La Paz
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP