KIDNEY TRANSPLANTATIONPhase 4OPTIMUSNCT03465410
OPTImization of the Dose of tacroliMUS by Bayesian Prediction
A Phase 4 study testing Standard dosage of Tacrolimus and Bayesian Prediction Tacrolimus dosage in people with KIDNEY TRANSPLANTATION, run by NURIA LLOBERAS BLANCH at 2 sites in Spain.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- KIDNEY TRANSPLANTATION
- What is being tested?
- Standard dosage of Tacrolimus and Bayesian Prediction Tacrolimus dosage
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 96 participants
- Where
- 2 sitesSpain
- Study dates
- 21 Mar 2017to 21 Sep 2020
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 12Show fewer
- 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.
Trial locations and contacts
2 sites in 1 country.
Spain2 sites
Hospital Universitari de la Vall d'Hebron
Barcelona
Hospital Universitari de Bellvitge
L'Hospitalet de Llobregat
About this study
Official title: 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
Read the 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.
- Conditions
- KIDNEY TRANSPLANTATION
- Being tested
- Standard dosage of Tacrolimus, Bayesian Prediction Tacrolimus dosage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standard dosage of TacrolimusDrug
Also called Tacrolimus
Immediate release Tacrolimus (Prograf/Adoport)
Bayesian Prediction Tacrolimus dosageDrug
Also called Tacrolimus
Immediate release Tacrolimus (Prograf/Adoport)
| Study group | Role | What they receive |
|---|---|---|
| GROUP I Standard adjustment | Active comparator | Standard dosage of Tacrolimus Receives: Drug: Standard dosage of Tacrolimus |
| GROUP II Bayesian prediction adjustment | Experimental | Bayesian prediction Tacrolimus dosage Receives: Drug: Bayesian Prediction Tacrolimus dosage |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tacrolimus plasmatic concentrations measurement
Concentration measured at day 6, 10, 15, 30, 60 and 90 post transplant and after each Tacrolimus dose adjustment
Measured: Day 6, 10, 15, 30, 60 and 90 post transplant
Secondary outcomes (2)
Time to achieve Tacrolimus therapeutic target levels
Time to achieve Tacrolimus therapeutic target levels within the 90 days post transplant
Measured: 90 days
Number of Tacrolimus dose changes to achieve target levels
Number of Tacrolimus dose changes to achieve target levels
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2018
- Study start21 Mar 2017
- Primary completion21 Sep 2020
- Study completion21 Sep 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for KIDNEY TRANSPLANTATIONStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A randomized, prospective, multicenter study
- Masking
- None (open label)
- Enrolment
- 96 participants (actual)
Sponsor and investigators
- Lead sponsor
- NURIA LLOBERAS BLANCH
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, NURIA LLOBERAS BLANCH, Hospital Universitari de Bellvitge
- Investigators
- Núria Lloberas, PhD, Principal investigator, Hospital Universitari de Bellvitge
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03465410
- Sponsor's protocol ID
- OPTIMUS
- Acronym
- OPTIMUS
- Status last verified
- Jan 2021
- First submitted
- 23 Feb 2018
- Last updated
- 8 Jan 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- OPTIMIZATION of the Dose of tacroliMUS by Bayesian Prediction in Renal Transplant Patients Including Pharmacogenetic Variables
- ClinicalTrials.gov ID
- NCT03465410
- Acronym / sponsor ID
- OPTIMUS / OPTIMUS
- Conditions
- KIDNEY TRANSPLANTATION
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 96 participants (actual)
- Lead sponsor
- NURIA LLOBERAS BLANCHUniversity, hospital or other
- Study start
- 21 Mar 2017 (actual)
- Primary completion
- 21 Sep 2020 (actual)
- Study completion
- 21 Sep 2020 (actual)
- First posted
- 14 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- A randomized, prospective, multicenter study
| Arm | Type | Receives |
|---|---|---|
| GROUP I Standard adjustment | Active comparator | Drug: Standard dosage of TacrolimusStandard dosage of Tacrolimus |
| GROUP II Bayesian prediction adjustment | Experimental | Drug: Bayesian Prediction Tacrolimus dosageBayesian prediction Tacrolimus dosage |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (12 listed)
- 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 .
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Standard dosage of TacrolimusAlso: TacrolimusImmediate release Tacrolimus (Prograf/Adoport) | Drug | GROUP I Standard adjustment |
| Bayesian Prediction Tacrolimus dosageAlso: TacrolimusImmediate release Tacrolimus (Prograf/Adoport) | Drug | GROUP II Bayesian prediction adjustment |
Primary outcome
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
2 secondary outcomes
Time to achieve Tacrolimus therapeutic target levels
Time frame: 90 days
Number of Tacrolimus dose changes to achieve target levels
Time frame: 90 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2021.
- Individual participant dataSharing planned: No
Related trials for KIDNEY TRANSPLANTATION
Enrolling by invitation
Online Exercise Program for Transplant Patients: A Pilot Study
Kidney Transplantation, Physical Function
RecruitingPhase 2
A Study of Mezagitamab in Adults With Late Antibody-Mediated Rejection (AMR) After a Kidney Transplant
Antibody-Mediated Rejection (AMR)
Not yet recruiting
Hypothermic Kidney Machine Perfusion With Omnisol
End Stage Renal Disease (ESRD), Kidney Transplant
Not yet recruitingEarly Phase 1
Biomarker-Guided Mycophenolate Mofetil Elimination in Low-Risk Older Adult Kidney Transplant Recipients
Kidney Transplant Recipient
Recruiting
Non-Invasive Monitoring of Pediatric Kidney Transplant Recipients and Immunosuppression Personalization: an Open-labeled Multicenter Randomized Controlled Study
Pediatric Kidney Disease, Transplant;Failure,Kidney
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Núria Lloberas, PhD principal investigator
Hospital Universitari de Bellvitge
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Standard dosage of Tacrolimus and Bayesian Prediction Tacrolimus dosage in people with KIDNEY TRANSPLANTATION, run by NURIA LLOBERAS BLANCH at 2 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Tacrolimus plasmatic concentrations measurement (time frame: Day 6, 10, 15, 30, 60 and 90 post transplant). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jan 2021; AzTrials last refreshed its copy on 6 Nov 2026.