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Trial record 51 of 1104 for:    pharmacogenomics OR pharmacogenetics

Individualized Antiretroviral Therapy (IAT)

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ClinicalTrials.gov Identifier: NCT03385473
Recruitment Status : Recruiting
First Posted : December 28, 2017
Last Update Posted : December 28, 2017
Sponsor:
Information provided by (Responsible Party):
Waldo Horacio Belloso, Hospital Italiano de Buenos Aires

Brief Summary:

The efficacy and safety of antiretroviral therapy and the damage caused by chronic inflammation in the presence of the virus has recently lead to the consideration of initiating antiretroviral therapy earlier than what is required to prevent opportunistic diseases.

Although there may be subtle differences, all recommended antiretroviral combinations for first-line therapy are considered equally effective. Nevertheless, treatment success requires high levels of adherence, which is linked to tolerability and the minimization of adverse effects.

The genes coding the enzymes that are involved in the antiretroviral clearance pathways and the transmembrane transport of drugs are known. These genetic variations can determine the interindividual variations in plasma concentration with the same doses. Both pharmacogenomics (PG) and therapeutic drug monitoring (TDM) may contribute to the individualization of therapy in different chronic conditions through dosing optimization and are associated with a lower risk of concentration-dependent toxicity and potentially greater efficacy. The use of these strategies in the context of antiretroviral therapy is in early stage of development.

Following, our main hypothesis is that PG + TDM dose adjustment of efavirenz or atazanavir in the initial antiretroviral treatment of naive patients with HIV infection is non-inferior in terms of efficacy, has improved safety, and shows a better cost/effectiveness profile than the standard approach with non adjusted doses.

To evaluate our hypothesis we developed this multicenter randomized clinical trial, where patients from 4 clinical sites in Buenos Aires will be included in the protocol and randomized to standard of care (SOC) or pharmacological adaptation (PA) -PA: PG + TDM. For the pharmacogenomics determination, we developed a multiplex approach including main polymorphisms of CYP2B6, CYP2A6, CYP3A4 y ABCB1 for efavirenz; and UGT1A1, ABCB1 and CYP3A4 for atazanavir. Drug plasma levels will be analyzed with ultra-performance liquid chromatography (UPLC).

The main outcomes are to establish the usefulness of PG and TDM in determining the efficacy, safety and cost/effectiveness of a first-line antiretroviral therapy containing either efavirenz or atazanavir in patients with HIV infection who have not received prior antiretroviral therapy.


Condition or disease Intervention/treatment Phase
Pharmacogenetics HIV Drug Monitoring Genetic: Pharmacogenomic index Diagnostic Test: Therapeutic drug monitoring Not Applicable

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Health Services Research
Official Title: Individualized Antiretroviral Therapy: Impact of Pharmacogenetic and Therapeutic Drug Monitoring in the Safety and Efficacy of First Line Antiretroviral Therapy in Patients With HIV Infection
Actual Study Start Date : October 5, 2017
Estimated Primary Completion Date : December 15, 2019
Estimated Study Completion Date : December 31, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Active Comparator: Pharmacological Adequation (PA)
Pharmacological adequation based on the Pharmacogenomic Index and therapeutic drug monitoring results.
Genetic: Pharmacogenomic index
All patients will have a blood sample drawn at randomization visits for PG analysis. For patients in the PA arm, the sample will be processed immediately to obtain the PG results and the subsequent index within 10 days. As soon as the results are available, the project team will contact the attending physician to propose the dosing adequation according to the pharmacogenomic index. PG analysis will be performed once for each patient.
Other Name: Diagnostic test

Diagnostic Test: Therapeutic drug monitoring
The patients included in the Pharmacological Adequation arm will have a TDM according to this schedule: day +14 (±3), +28 (±3), and +168 (±3). If there is an abnormal value (out of the therapeutic range), we will proceed to adjust the prescription.
Other Name: TDM

No Intervention: Standard of Care (SOC)
Without pharmacological adequation



Primary Outcome Measures :
  1. Feasibility of implementation of a multicenter study to analyze pharmacological adequation and therapeutic drug monitoring of efavirenz or atazanavir in the initial antiretroviral treatment of naive patients with HIV infection [ Time Frame: 48 Weeks ]
    Number of days between obtention of study samples and availability of test results (turnaround time)


Secondary Outcome Measures :
  1. Frequency of adverse events [ Time Frame: 48 Weeks ]
    Pharmacological Adequation arm of efavirenz or atazanavir in the initial antiretroviral treatment of naive patients with HIV infection will show reduced frequency of adverse events when compared with the Standard Prescription arm.

  2. Efficacy of antiretroviral treatment [ Time Frame: 48 weeks ]
    Pharmacological Adequation arm of efavirenz or atazanavir performs equally to the standard of care arm. Viral load at 48 weeks aimed to be non inferior between arms, analyzed through FDA-recommended Snapshot approach.

  3. Cost/effectiveness compared in both arms [ Time Frame: 48 Weeks ]
    Pharmacological Adequation arm of efavirenz or atazanavir in the initial antiretroviral treatment of naive patients with HIV infection shows a better cost/effectiveness profile than the standard of care approach. (Direct Cost analysis)



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult patients with diagnosis of chronic HIV infection confirmed by Western blot and / or HIV viral load
  • Patients in whom (according to the judgment of the treating physician) antiretroviral therapy should be initiated and this treatment will be a regimen based on Efavirenz or Atazanavir.
  • Availability of a baseline genotyping test confirming the absence of primary resistance for the selected drugs.
  • Signature of the informed Consent Form

Exclusion Criteria:

  • Patients who remain untreated or those treated with a regimen that does not include efavirenz or atazanavir
  • Lack of understanding of the study characteristics or rejection to have samples taken for the pharmacological studies.
  • Patients who are not expected to continue their follow-up at the research center for at least one year
  • Patients with coinfections or comorbidities that prevent a dose adjustment of efavirenz or atazanavir based on pharmacological parameters.

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): NCT03385473


Contacts
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Contact: Waldo H Belloso, MD 00 54 11 4959 0200 ext 4153 waldo.belloso@hospitalitaliano.org.ar

Locations
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Argentina
Hospital Italiano de Buenos Aires - Infectious Diseases Section Recruiting
Buenos Aires, Caba, Argentina, 1181
Contact: Waldo H Belloso, MD    5411 4959 0200 ext 4153    waldo.belloso@hospitalitaliano.org.ar   
Contact: Paula Scibona, MD    5411 4959 0200 ext 4153    paula.scibona@hospitalitaliano.org.ar   
Principal Investigator: Waldo H Belloso, MD         
Sponsors and Collaborators
Hospital Italiano de Buenos Aires
Investigators
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Principal Investigator: Waldo H Belloso, MD Hospital Italiano de Buenos Aires

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Responsible Party: Waldo Horacio Belloso, MD, Hospital Italiano de Buenos Aires
ClinicalTrials.gov Identifier: NCT03385473     History of Changes
Other Study ID Numbers: 1901
First Posted: December 28, 2017    Key Record Dates
Last Update Posted: December 28, 2017
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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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Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents