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

Primary Purpose

Invasive Fungal Infections

Status
Unknown status
Phase
Phase 4
Locations
Spain
Study Type
Interventional
Intervention
Voriconazole preemptive genotyping strategy
Voriconazole clinical practice
Sponsored by
Instituto de Investigación Hospital Universitario La Paz
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Invasive Fungal Infections

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • La Paz University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Experimental group

Control group

Arm Description

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.

No information will be provided and procedure will be carried out according to normal clinical practice, with clinical monitoring by the doctor in charge.

Outcomes

Primary Outcome Measures

Serum voriconazole concentration
Serum voriconazole concentration within the therapeutic range, in μg/mL.

Secondary Outcome Measures

Therapeutic failure
% of patients with therapeutic failure. A patient has a therapeutic failure if: In patient with suspected or confirmed invasive aspergillosis: drug change or association, because of bad clinical or radiological evolution of the disease. In patient who receive prophylactic treatment: the necessity of change because of suspected or confirmed invasive fungal disease.
Adverse event
% 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
Quantifying economic burden (in euros) associated with management of severe adverse events.
Quality adjusted life years (QALY)
Measure of disease burden, including both the quality and the quantity of life lived.

Full Information

First Posted
January 18, 2020
Last Updated
January 22, 2020
Sponsor
Instituto de Investigación Hospital Universitario La Paz
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1. Study Identification

Unique Protocol Identification Number
NCT04238884
Brief Title
Effectiveness and Efficiency of a Voriconazole Preemptive Genotyping Strategy
Acronym
VORIGENPHARM
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

2. Study Status

Record Verification Date
January 2020
Overall Recruitment Status
Unknown status
Study Start Date
January 2, 2020 (Actual)
Primary Completion Date
January 18, 2020 (Actual)
Study Completion Date
December 31, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Instituto de Investigación Hospital Universitario La Paz

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Invasive Fungal Infections

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
146 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Experimental group
Arm Type
Experimental
Arm Description
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.
Arm Title
Control group
Arm Type
Active Comparator
Arm Description
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 Type
Drug
Intervention Name(s)
Voriconazole preemptive genotyping strategy
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Voriconazole clinical practice
Intervention Description
The patients who finally receives voriconazole will be randomized to receive the dose according to clinical practice
Primary Outcome Measure Information:
Title
Serum voriconazole concentration
Description
Serum voriconazole concentration within the therapeutic range, in μg/mL.
Time Frame
Day 5 of treatment
Secondary Outcome Measure Information:
Title
Therapeutic failure
Description
% of patients with therapeutic failure. A patient has a therapeutic failure if: In patient with suspected or confirmed invasive aspergillosis: drug change or association, because of bad clinical or radiological evolution of the disease. In patient who receive prophylactic treatment: the necessity of change because of suspected or confirmed invasive fungal disease.
Time Frame
Within 3 months
Title
Adverse event
Description
% 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
Time Frame
Within 3 months
Title
Costs by adverse event
Description
Quantifying economic burden (in euros) associated with management of severe adverse events.
Time Frame
Day 90 of treatment
Title
Quality adjusted life years (QALY)
Description
Measure of disease burden, including both the quality and the quantity of life lived.
Time Frame
Day 90 of treatment

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Those who agree to participate in the study by signing informed consent (patients equal or over 18 years old) Subjects under 18 years old whose representative / legal guardian has voluntarily signed the informed consent. 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: Patients who for any reason should not be included in the study according to the criteria of the research team. Subjects who are not capable to understand the information sheet and unable to sign the informed consent.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Alberto M Borobia, MD, PhD
Phone
+34-917277558
Email
alberto.borobia@salud.madrid.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alberto M Borobia, MD, PhD
Organizational Affiliation
La Paz University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
La Paz University Hospital
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alberto M Borobia, PI
Phone
+34917277558
Email
alberto.borobia@salud.madrid.org

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
33004392
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.
Results Reference
derived

Learn more about this trial

Effectiveness and Efficiency of a Voriconazole Preemptive Genotyping Strategy

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