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

January 22, 2020 updated by: Instituto de Investigación Hospital Universitario La Paz

Randomized and Multicenter Clinical Trial to Evaluate the Effectiveness and Efficiency of a Voriconazole Preemptive Genotyping Strategy in Patients With Risk of Aspergillosis

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Anticipated)

146

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • ADULT
  • OLDER_ADULT
  • CHILD

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: SINGLE

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Serum voriconazole concentration
Time Frame: Day 5 of treatment
Serum voriconazole concentration within the therapeutic range, in μg/mL.
Day 5 of treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Within 3 months
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
Within 3 months
Costs by adverse event
Time Frame: Day 90 of treatment
Quantifying economic burden (in euros) associated with management of severe adverse events.
Day 90 of treatment
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.
Day 90 of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Instituto de Investigación Hospital Universitario La Paz

Investigators

  • Principal Investigator: Alberto M Borobia, MD, PhD, La Paz University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

January 2, 2020

Primary Completion (ACTUAL)

January 18, 2020

Study Completion (ANTICIPATED)

December 31, 2022

Study Registration Dates

First Submitted

January 18, 2020

First Submitted That Met QC Criteria

January 22, 2020

First Posted (ACTUAL)

January 23, 2020

Study Record Updates

Last Update Posted (ACTUAL)

January 23, 2020

Last Update Submitted That Met QC Criteria

January 22, 2020

Last Verified

January 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2019-000376-41

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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