Renal Transplant RejectionPhase 4NCT03511560
Envarsus on the Effect of Total Tacrolimus Dose/Trough Level Ratio on Renal Function (eGFR) in Kidney Transplantation
A Phase 4 study testing Tacrolimus Extended Release Oral Tablet and Tacrolimus in people with Renal Transplant Rejection and Kidney Transplant Failure and Rejection, run by Columbia University at 1 site in United States.
Trial summary
This is a one year, prospective, randomized, open-label trial examining once versus twice daily tacrolimus dosing regimen using two preparations, extended-release Tacrolimus (Envarsus XR) versus twice daily Tacrolimus (Prograf). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Renal Transplant Rejection, Kidney Transplant Failure and Rejection
- What is being tested?
- Tacrolimus Extended Release Oral Tablet and Tacrolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Jul 2018to 17 Jul 2021
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Kidney transplant patient ≥ 18 years and ≤ 80 years old
- Institutional Review Board (IRB) approved written Informed Consent and privacy language must be obtained from the subject or legally authorized representative prior to any study-related procedures (including withdrawal of prohibited medication, if applicable).
- Recipient of a de novo kidney from a living or deceased donor.
- If deceased donor, a Kidney Donor Profile Index (KDPI) ≤ 85% are eligible for enrollment.
- Willingness to comply with study protocol.
- Previous kidney transplants will be permitted. Patients who are receiving a secondary transplant and who previously received Envarsus or who are currently on Envarsus as a component of maintenance immunosuppression and re-listed for transplant will be eligible to enroll in this study and will be randomized at the time of transplant to either cohort.
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- Subject agrees not to participate in another study while on treatment.
- Female subject must be either:
- Of non-child-bearing potential,
- Post-menopausal (defined as at least 1 year without any menses) prior to screening, or
- Documented surgically sterile or status post-hysterectomy
- Or, if of childbearing potential,
- Agree not to try to become pregnant during the study and for 90 days after the final study drug administration
- And have a negative serum or urine pregnancy test within 7 days prior to transplant procedure
- And, if heterosexually active, agree to consistently use two forms of highly effective birth control (at least one of which must be a barrier method) which includes consistent and correct usage of established oral contraception, established intrauterine device or intrauterine system , or barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, starting at screening and throughout the study period and for 90 days after the final study drug administration.
Who cannot join
- Patient is known to have a positive test for latent tuberculosis (TB) and has not previously received adequate anti-microbial therapy or would require TB prophylaxis after transplant.
- Uncontrolled concomitant infection or any unstable medical condition that could interfere with study objectives.
- Significant liver disease, defined as having, during the past 28 days, consistently elevated aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase (SGOT)) and/or alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase (SPGT)) levels greater than 3 times the upper value of the normal range of the investigational site.
- Patient who will be maintained on a non-tacrolimus-based maintenance immunosuppressive regimen following his/her transplant procedure.
- Patient currently taking, having taken within 30 days, or who will be maintained on an mechanistic target of rapamycin (mTOR) inhibitor following his/her transplant procedure.
- Use of an investigational study drug in the 30 days prior to the transplant procedure.
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- Contraindication or hypersensitivity to drugs or any of their components that constitute the immunosuppression regimen.
- Known infection or seropositivity for HIV (HBsAg and Hepatitis C (HCV) positivity with negative viral load permitted).
- Focal segmental glomerulosclerosis.
- Subject has a current malignancy or history of malignancy (within the past 2 years), except non-metastatic basal or squamous cell carcinoma of the skin or carcinoma-in- situ of the cervix that has been successfully treated.
- Recipient of multi-organ kidney transplants.
- Recipient of an en bloc, adult or pediatric deceased donor kidney
- Any condition which, in the investigator's opinion, makes the subject unsuitable for study participation.
Trial locations and contacts
1 site in 1 country.
United States1 site
Columbia University Medical Center
New York, New York, 10032
About this study
Official title: To Understand the Impact of Immunosuppression Using Once-per-day Envarsus XR on the Effect of Total Tacrolimus Dose/Trough Level Ratio on Renal Function (eGFR) in Kidney Transplantation
This is a one year, prospective, randomized, open-label trial examining once versus twice daily tacrolimus dosing regimen using two preparations, extended-release Tacrolimus (Envarsus XR) versus twice daily Tacrolimus (Prograf). It will examine kidney function between the two groups using estimated glomerular filtration rate (eGFR) and also examine one-year kidney outcomes, including graft loss and patient death. Patients will be followed for up to 1 year during the open-label study period.
Read the detailed description
Despite lower rates of acute rejection and short-term improvements in patient and graft survival, the rate of late allograft loss following kidney transplantation has remained unchanged. Achievement of therapeutic, minimally toxic, tacrolimus concentrations early (within 30 days), after transplantation, is known to be important since achieving it has been associated with a lowered risk of acute rejection. The investigators hypothesize that using extended release tacrolimus (Envarsus XR, Veloxis), will provide more stable, more effective, and less toxic levels of tacrolimus in renal allograft recipients. Therefore, the investigators propose to analyze the impact of the blood concentration normalized by the dose (C/D ratio) on kidney function after renal transplantation in experimental group that will be treated with Envarsus XR and the standard of care (SOC) group treated with twice a day tacrolimus.
- Being tested
- Tacrolimus Extended Release Oral Tablet, Tacrolimus
- Keywords
- Envarsus XR, Tacrolimus, Kidney Transplantation
- Medical subject headings
- Rejection, Psychology
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tacrolimus Extended Release Oral TabletDrug
Also called Envarsus XR
Tacrolimus, extended-release, oral (Envarsus); 0.75 mg, 1 mg, 4 mg tablets will be administered once daily at initial weight-based dose of 0.12 mg/kg.
TacrolimusDrug
Also called Prograf
Tacrolimus immediate-release, oral; 0.5 mg, 1 mg, 5 mg capsules will be administered twice daily per clinical judgment of supervising physician
| Study group | Role | What they receive |
|---|---|---|
| Tacrolimus, Immediate release | Active comparator | Tacrolimus (immediate-release) will be administered twice daily per clinical judgment of supervising physician (dosing and monitoring in accordance with center protocol) to a minimum whole blood tacrolimus concentration of at least 8 ng/mL. Receives: Drug: Tacrolimus |
| Envarsus XR | Experimental | Envarsus XR (Tacrolimus Extended Release Oral Tablet) will be administered once daily at initial weight-based dose of 0.12 mg/kg. Dosing and monitoring thereafter predicated on clinical judgment to a minimum whole blood tacrolimus concentration of at least 8 ng/mL. When possible, patients will receive their daily dose of Envarsus using the fewest number of pills possible. Receives: Drug: Tacrolimus Extended Release Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean C/D Ratio
Tacrolimus metabolism was determined for all dates of tacrolimus blood trough concentration collection after renal transplantation by dividing the tacrolimus blood trough concentration (C) by the corresponding total daily tacrolimus dose (D).
C/D ratio (ng/mL*1/mg) = blood tacrolimus trough level (ng/mL)/total daily tacrolimus dose (mg).
Measured: Every Month for up to 1 year
Secondary outcomes (4)
Mean Serum Creatinine Level
Serum creatinine levels were measured to assess kidney function following transplantation
Measured: 12 months
Patient Survival Rate
Patient survival is any subject that is known to be alive at the study conclusion.
Measured: 12 months
Graft Survival Rate
Graft survival is defined as any subject that does not fit the following definition of graft loss: subject death, re-transplantation, transplant nephrectomy, or return to dialysis for a period of ≥6 weeks by study end.
Measured: 12 months
Number of Rejection Episodes
For study purposes, diagnoses of rejection require biopsy confirmation.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2018
- Study start26 Jul 2018
- Primary completion17 Jul 2020
- Study completion17 Jul 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Renal Transplant RejectionStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a prospective, randomized, open-label trial examining once versus twice daily tacrolimus dosing regimen using two preparations, Envarsus vs Prograf
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Collaborators
- Veloxis Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Mark Hardy, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03511560
- Sponsor's protocol ID
- AAAR6805
- Status last verified
- Jun 2024
- First submitted
- 29 Jan 2018
- Last updated
- 17 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- To Understand the Impact of Immunosuppression Using Once-per-day Envarsus XR on the Effect of Total Tacrolimus Dose/Trough Level Ratio on Renal Function (eGFR) in Kidney Transplantation
- ClinicalTrials.gov ID
- NCT03511560
- Acronym / sponsor ID
- AAAR6805
- Keywords
- Envarsus XR, Tacrolimus, Kidney Transplantation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Collaborators
- Veloxis Pharmaceuticals
- Study start
- 26 Jul 2018 (actual)
- Primary completion
- 17 Jul 2020 (actual)
- Study completion
- 17 Jul 2021 (actual)
- First posted
- 30 Apr 2018 (actual)
- Results
- Posted 17 Jul 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a one year, prospective, randomized, open-label trial examining once versus twice daily tacrolimus dosing regimen using two preparations, extended-release Tacrolimus (Envarsus XR) versus twice daily Tacrolimus (Prograf). It will examine kidney function between the two groups using estimated glomerular filtration rate (eGFR) and also examine one-year kidney outcomes, including graft loss and patient death. Patients will be followed for up to 1 year during the open-label study period.
Detailed description
Despite lower rates of acute rejection and short-term improvements in patient and graft survival, the rate of late allograft loss following kidney transplantation has remained unchanged. Achievement of therapeutic, minimally toxic, tacrolimus concentrations early (within 30 days), after transplantation, is known to be important since achieving it has been associated with a lowered risk of acute rejection. The investigators hypothesize that using extended release tacrolimus (Envarsus XR, Veloxis), will provide more stable, more effective, and less toxic levels of tacrolimus in renal allograft recipients. Therefore, the investigators propose to analyze the impact of the blood concentration normalized by the dose (C/D ratio) on kidney function after renal transplantation in experimental group that will be treated with Envarsus XR and the standard of care (SOC) group treated with twice a day tacrolimus.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This is a prospective, randomized, open-label trial examining once versus twice daily tacrolimus dosing regimen using two preparations, Envarsus vs Prograf
| Arm | Type | Receives |
|---|---|---|
| Tacrolimus, Immediate release | Active comparator | Drug: TacrolimusTacrolimus (immediate-release) will be administered twice daily per clinical judgment of supervising physician (dosing and monitoring in accordance with center protocol) to a minimum whole blood tacrolimus concentration of at least 8 ng/mL. |
| Envarsus XR | Experimental | Drug: Tacrolimus Extended Release Oral TabletEnvarsus XR (Tacrolimus Extended Release Oral Tablet) will be administered once daily at initial weight-based dose of 0.12 mg/kg. Dosing and monitoring thereafter predicated on clinical judgment to a minimum whole blood tacrolimus concentration of at least 8 ng/mL. When possible, patients will receive their daily dose of Envarsus using the fewest number of pills possible. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Kidney transplant patient ≥ 18 years and ≤ 80 years old
- Institutional Review Board (IRB) approved written Informed Consent and privacy language must be obtained from the subject or legally authorized representative prior to any study-related procedures (including withdrawal of prohibited medication, if applicable).
- Recipient of a de novo kidney from a living or deceased donor.
- Willingness to comply with study protocol.
- Previous kidney transplants will be permitted. Patients who are receiving a secondary transplant and who previously received Envarsus or who are currently on Envarsus as a component of maintenance immunosuppression and re-listed for transplant will be eligible to enroll in this study and will be randomized at the time of transplant to either cohort.
Key exclusion criteria (13 listed)
- Patient is known to have a positive test for latent tuberculosis (TB) and has not previously received adequate anti-microbial therapy or would require TB prophylaxis after transplant.
- Uncontrolled concomitant infection or any unstable medical condition that could interfere with study objectives.
- Significant liver disease, defined as having, during the past 28 days, consistently elevated aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase (SGOT)) and/or alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase (SPGT)) levels greater than 3 times the upper value of the normal range of the investigational site.
- Patient who will be maintained on a non-tacrolimus-based maintenance immunosuppressive regimen following his/her transplant procedure.
- Patient currently taking, having taken within 30 days, or who will be maintained on an mechanistic target of rapamycin (mTOR) inhibitor following his/her transplant procedure.
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 |
|---|---|---|
| Tacrolimus Extended Release Oral TabletAlso: Envarsus XRTacrolimus, extended-release, oral (Envarsus); 0.75 mg, 1 mg, 4 mg tablets will be administered once daily at initial weight-based dose of 0.12 mg/kg. | Drug | Envarsus XR |
| TacrolimusAlso: PrografTacrolimus immediate-release, oral; 0.5 mg, 1 mg, 5 mg capsules will be administered twice daily per clinical judgment of supervising physician | Drug | Tacrolimus, Immediate release |
Primary outcome
Mean C/D Ratio
Time frame: Every Month for up to 1 year
Tacrolimus metabolism was determined for all dates of tacrolimus blood trough concentration collection after renal transplantation by dividing the tacrolimus blood trough concentration (C) by the corresponding total daily tacrolimus dose (D). C/D ratio (ng/mL*1/mg) = blood tacrolimus trough level (ng/mL)/total daily tacrolimus dose (mg).
4 secondary outcomes
Mean Serum Creatinine Level
Time frame: 12 months
Patient Survival Rate
Time frame: 12 months
Graft Survival Rate
Time frame: 12 months
Number of Rejection Episodes
Time frame: 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Mark Hardy, MD principal investigator
Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Tacrolimus Extended Release Oral Tablet and Tacrolimus in people with Renal Transplant Rejection and Kidney Transplant Failure and Rejection, run by Columbia University at 1 site in United States.
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 15 inclusion and 13 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 17 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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?
Yes. Results are posted in the registry (first posted 17 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Mean C/D Ratio (time frame: Every Month for up to 1 year). 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 17 Jul 2024.