OPTImization of the Dose of tacroliMUS by Bayesian Prediction (OPTIMUS)

January 7, 2021 updated by: NURIA LLOBERAS BLANCH

OPTIMIZATION of the Dose of tacroliMUS by Bayesian Prediction in Renal Transplant Patients Including Pharmacogenetic Variables

The pharmacokinetics of tacrolimus (TAC) are characterized by high inter- and intra-individual variability with narrow therapeutic range. Currently, the limiting point of Tac drug monitoring is the inability to individualize doses during the first few days after transplantation. Our group developed a population pharmacokinetic model (PPK) identifying CYP3A4 * 22 and CYP3A5 * 3 polymorphisms and hematocrit as explanatory variables of the observed variability in pre-dose (Co) concentrations. According to this model, the proportion of patients that do not reach the therapeutic target is 40

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The results of the study of genetic polymorphisms performed in renal transplant patients at our hospital demonstrated the influence of CYP3A5 * 3 and CYP3A4 * 22 single nucleotide polymorphism (SNPs) on exposure to Tac. From these results, the first population pharmacokinetic model was developed, which included CYP3A5 * 3 and CYP3A4 * 22 polymorphisms as well as hematocrit as explanatory variables of interindividual variability. Based on our population model and using the simulation tool, the percentage of patients reaching the therapeutic target based on Co values within the range of 6-10 ng / mL was determined after being dosed according to the strategy of Conventional dosage empirically according to Co achieved. The simulation of 50 Co values according to the conventional dosage allowed to determine the proportion of patients reaching the therapeutic target in each case and their confidence interval. 40% of the patients did not reach the therapeutic objective. Based on the clusters of the two polymorphisms, the percentages of patients on or below exposed varied according to whether they were slow or fast metabolizers respectively. Due to this high variability in Tac PK, the individualization of the Tac posology was calculated by calculating the initial dose according to the population model previously developed and adjusting the subsequent doses, as a function of the Tac Co through Bayesian approximations with the inclusion of genotyping and Hematocrit, can contribute greatly to achieve optimal exposure to the drug from the start of treatment in the immediate post-transplant and reduce the variability observed in the Co-achieved; This may be particularly important for patients with a slow and rapid metabolizer profile. All of this may contribute to minimizing adverse effects, ensuring greater efficacy in the target population, reducing the risk of acute rejection, and reducing associated costs.

In the present study we intend to incorporate pharmacogenomics for its application in de novo patients, which will allow us to perform a more individualized therapy for each patient based on the values of target Co and the CYP3A5 * 3 and CYP3 A4 * 22 polymorphisms of the patient since The initiation of immunosuppressive therapy and thus improve efficiency and decrease adverse effects.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
96

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

  • Spain
      • Barcelona, Spain
        • Hospital Universitari de la Vall d'Hebron
      • L'Hospitalet De Llobregat, Spain
        • Hospital Universitari de Bellvitge

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Kidney transplant recipients, from cadaveric and living donor.
  • Patients that are going to receive immediate release Tacrolimus (Prograf/Adoport) as part of immunosuppressive treatment.
  • Concomitant immunosuppression with Mycophenolate mofetil/Mycophenolic acid and steroids.
  • Induction with Basiliximab is permitted.
  • Subjects able to provide written informed consent.
  • Female subjects of child-bearing potential must have a negative serum pregnancy test and must be practicing an effective, reliable, and medically approved contraceptive regimen during the study.

Exclusion Criteria:

  • Subjects treated with drugs that can potentially interfere with Tacrolimus, especially CYP3A4 inhibitors (telaprevir, boceprevir, ritonavir, ketoconazole, voriconazole, itraconazole, telithromycin or clarithromycin) or CYP3A4 inductors (rifampicin or rifabutine).
  • Subjects that receive induction treatment with Thymoglobulin or rituximab.
  • Subjects participating in another investigational study within 30 days before inclusion.
  • Subjects with hepatopathy.
  • Subject or donor with a history of any malignancy (within the past 5 years), except non-metastatic basal or squamous cell carcinoma of the skin .
  • Female subjects who are pregnant or breast feeding.
  • Subjects receiving an ABO incompatible kidney.
  • Subjects have Donor Specific Antibodies.
  • Recipients of an allograft with ischemic cold time > or = 24 hours.
  • Subjects with a history of active hepatitis C virus (HCV-RNA positive) and/or hepatitis B virus (DNA-HBV or HBsAg positive) infection.
  • Subjects with a history of human immunodeficiency virus (HIV-Ab positive) infection.
  • Subjects with psychiatric or physical illness that could interfere with the ability of the subject to participate in the study.

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: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
ACTIVE_COMPARATOR: GROUP I Standard adjustment
Standard dosage of Tacrolimus
Drug: Standard dosage of Tacrolimus
Immediate release Tacrolimus (Prograf/Adoport)
Other Names:
  • Tacrolimus
EXPERIMENTAL: GROUP II Bayesian prediction adjustment
Bayesian prediction Tacrolimus dosage
Drug: Bayesian Prediction Tacrolimus dosage
Immediate release Tacrolimus (Prograf/Adoport)
Other Names:
  • Tacrolimus

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Tacrolimus plasmatic concentrations measurement
Time Frame: Day 6, 10, 15, 30, 60 and 90 post transplant
Concentration measured at day 6, 10, 15, 30, 60 and 90 post transplant and after each Tacrolimus dose adjustment
Day 6, 10, 15, 30, 60 and 90 post transplant

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Time to achieve Tacrolimus therapeutic target levels
Time Frame: 90 days
Time to achieve Tacrolimus therapeutic target levels within the 90 days post transplant
90 days
Number of Tacrolimus dose changes to achieve target levels
Time Frame: 90 days
Number of Tacrolimus dose changes to achieve target levels
90 days

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
NURIA LLOBERAS BLANCH

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Núria Lloberas, PhD, Hospital Universitari de Bellvitge

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 21, 2017

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 21, 2020

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 21, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 23, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 13, 2018

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 14, 2018

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 8, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 7, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • OPTIMUS

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

product manufactured in and exported from the U.S.

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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