Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Prospective Pilot Feasibility Study Comparing Envarsus Once-a-day to Tacrolimus Twice-a-day Immunosuppressive Regimen on Drug Bioavailability in Hispanic First Time Kidney Transplant Recipients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03438773
Recruitment Status : Recruiting
First Posted : February 20, 2018
Last Update Posted : June 4, 2019
Sponsor:
Collaborators:
Balboa Institute of Transplantation
University of California, San Diego
Information provided by (Responsible Party):
California Institute of Renal Research

Brief Summary:
This investigator-initiated post-marketing study will evaluate the role of Hispanic ethnicity on drug dosing of Envarsus in first-time stable renal transplant recipients. Tacrolimus trough drug levels will be studied as a primary endpoint at 24 hours after drug dosing and at steady state (e.g., trough level at 3 months post conversion) and secondary compliance assessments will be done by pill counts at clinic visits. Secondary outcomes will be the safety of once a day dosing as well as assessment of graft rejection and graft failure. In addition, concentration/dose ratios will be analyzed. The results of this study will provide important information about dosing of once a day tacrolimus (Envarsus) in Hispanic kidney transplant patients, which represents the largest growing group of patients with End-Stage Renal Disease

Condition or disease Intervention/treatment Phase
Kidney Transplant; Complications Kidney Transplant Failure and Rejection Drug: Envarsus Drug: Tacrolimus Phase 1

Detailed Description:

Adequate drug dosing is essential to prevent allograft rejection and subsequent allograft loss. Many studies have shown that serum levels of immunosuppressant medications can be strongly influenced by the patient's genetic profile. Genetics has been shown to influence tacrolimus drug dosing in both liver and kidney transplant recipients 1. Whether these genetic differences influence care in clinical practice though is not known. Several genetic influences have been identified in Hispanic patients, such as polymorphisms in Cytochrome genes 1 and Nuclear Factor-kappa B genes 2, that might influence tacrolimus dosing and blood levels. In a study of Hispanic children, significant correlations were found to suggest that ethnic differences resulted in the need for higher or more frequent tacrolimus doing in Hispanic children 3. According to the Centers for Disease Control, Hispanics are 1.5 times as likely as non-Hispanic whites to develop ESRD 4 and Hispanics are the largest minority with the fastest growth of ESRD in the United States 5. Therefore it is likely that the unanswered question of whether there are differences in bioavailability of Envarsus in Hispanic patients will become even more relevant over time. Strategies that target improved bioavailability have the opportunity to significantly improve outcomes for all recipients of kidney transplants. Specifically, vulnerable patient populations, such as Hispanic patients, need to be studied to better understand the potential for altered bioavailability of immunosuppressive medications based on inherited pharmacologic traits.

Providing patients a once-a-day option for their immunosuppressive medication dosing is predicted to improve adherence, but whether once daily Envarsus provides adequate drug levels in Hispanic patient groups is not known. This study will carefully evaluate drug levels as a primary endpoint in this investigator-initiated study. Additional secondary outcomes to be measured over the two years of the study will be allograft rejection and allograft loss. The hypothesis of this study is that kidney transplant recipients receiving once-a-day extended release tacrolimus (Envarsus) will have outcomes that are not inferior to those who received twice-a-day tacrolimus during the two-year study period.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Patients randomized into the study group will be prescribed Envarsus, mycophenolate and prednisone as a regimen vs. standard therapy with twice a day tacrolimus, mycophenolate and prednisone.

Patients randomized to the control group will be prescribed standard immunosuppression with tacrolimus twice a day, anti-proliferative twice a day, and prednisone once a day at doses that are standard at our institution.

Masking: None (Open Label)
Primary Purpose: Other
Official Title: Prospective Pilot Feasibility Study Comparing Envarsus Once-a-day to Tacrolimus Twice-a-day Immunosuppressive Regimen on Drug Bioavailability in Hispanic First Time Kidney Transplant Recipients
Actual Study Start Date : July 11, 2018
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : July 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Tacrolimus

Arm Intervention/treatment
Envarsus
Study group - Envarsus once daily in addition to standard of care.
Drug: Envarsus
Patients randomized into the Envarsus group will be prescribed Envarsus, mycophenolate and prednisone once daily.

Tacrolimus
Control group - Tacrolimus twice daily in addition to standard of care.
Drug: Tacrolimus
Patients randomized to the Tacrolimus group will be prescribed Tacrolimus twice-daily with standard of care immunosuppression, anti-proliferative and prednisone once-daily.




Primary Outcome Measures :
  1. Tacrolimus drug levels [ Time Frame: 2 years ]
    Tacrolimus trough drug levels will be studied as a primary endpoint at 24 hours after drug dosing and at steady state through local lab HPLC MS/MS assays.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion Criteria:

  • Male or Female 18 years of age or older.
  • The subject is a first time stable renal transplant patients, who have received their transplant at least 3 months before study entry.
  • The subject is willing to commit to the study design.
  • The subject is considered to have stable allograft function defined as no documented rejection episodes within one month of screening.
  • The subject is not currently receiving treatment with other experimental therapies directed at their transplant.

Exclusion Criteria:

  • The subject has undergone a prior organ or bone marrow transplant.
  • The subject has taken any interacting/contraindicated drug determined by the Investigator within 30 days of administration of the protocol.
  • Any study drug allergies and if there are high serum donor specific antibody levels (DSA) or a high panel reactive antibody level (PRA).
  • Documented treatment of rejection within 30 days of onset of the screening visit.

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): NCT03438773


Contacts
Layout table for location contacts
Contact: Michael C Gastauer 858-810-8155 mgastauer@balboaunited.org
Contact: Eva Gripp, LVN 858-637-4600 EGripp@balboaunited.org

Locations
Layout table for location information
United States, California
California Institute of Renal Research Recruiting
San Diego, California, United States, 92123
Contact: Eva Gripp, LVN    858-637-4600    EGripp@balboaunited.org   
Contact: Karina Maldonado    858-810-8083    KMaldonado@balboaunited.org   
Principal Investigator: Arman Faravardeh, MD         
Sub-Investigator: Steven Steinberg, MD         
Sponsors and Collaborators
California Institute of Renal Research
Balboa Institute of Transplantation
University of California, San Diego
Investigators
Layout table for investigator information
Principal Investigator: Arman Faravardeh, MD California Institute of Renal Research

Layout table for additonal information
Responsible Party: California Institute of Renal Research
ClinicalTrials.gov Identifier: NCT03438773     History of Changes
Other Study ID Numbers: VLX001-17
v01 01-Sep-2017 ( Other Identifier: California Institute of Renal Research )
First Posted: February 20, 2018    Key Record Dates
Last Update Posted: June 4, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by California Institute of Renal Research:
Hispanic
First time kidney recipients

Additional relevant MeSH terms:
Layout table for MeSH terms
Tacrolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action