AllograftPhase 4ENVARSWITCHNCT02882828
PK Assessment of Tacrolimus Exposure Before and After a Switch From Twice Daily Immediate-release (Prograf®) to Once-daily Prolonged Release Tacrolimus (Envarsus®)
A Phase 4 study testing switched from Prograf® to Envarsus® in people with Allograft, run by University Hospital, Limoges at 9 sites in France.
Trial summary
Tools have been developed in our unit to calculate the inter-dose AUC (Area Under Curve) of immunosuppressive drugs (ISD) based on a limited number of blood concentrations (i.e., blood samples) using Bayesian methods. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Allograft
- What is being tested?
- switched from Prograf® to Envarsus®
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 134 participants
- Where
- 9 sitesFrance
- Study dates
- Oct 2016to Mar 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
- Adult (≥ 18 year-old) male and female patients
- Recipient of a single kidney or liver allograft
- Patient transplanted for more than 2 weeks and less than 1 year at enrolment
- Patient with stable Prograf® dose, defined by the following criteria:
- Criterion 1: unchanged Prograf® dose for at least one week; if not, apply criterion #2
- Criterion 2: unchanged Prograf® dose since the last two therapeutic drug monitorings (TDM)
Show all 10Show fewer
- Patient for whom the decision is made to switch from Prograf® to Envarsus®
- Written informed consent obtained prior to any study-related procedure
- Patient with tacrolimus C0 between 4 and 12 µg/L at V1
- Patient with hematocrit > 27% at V1
Who cannot join
- Patient presenting any contra-indication to tacrolimus according to the summary of product characteristics (SmPC) of Envarsus®
- Recipient of any transplanted organ other than kidney or liver
- Patient treated by Prograf® for less than 7 days at enrolment
- Patient previously treated by any other investigational agent if it is not stopped at least 7 days prior to enrolment
- Pregnant or lactating woman (based on declaration)
- Patient under judicial protection
- Patient incapable of understanding the purposes and risks of the study, who cannot give written informed consent, or who are unwilling to comply with the study protocol.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
France9 sites
University Hospital of Amiens
Amiens
University Hospital of Bordeaux
Bordeaux
University Hospital of Lille
Lille
Limoges Hospital
Limoges, 87 042
AP-HP
Paris
University Hospital of Poitiers
Poitiers
University Hospital of Reims
Reims
University Hospital of Rouen
Rouen
University Hospital of Tours
Tours
About this study
Official title: Pharmacokinetic Assessment of Tacrolimus Exposure Before and After a Switch From Twice Daily Immediate-release (Prograf®) to Once-daily Prolonged Release Tacrolimus (Envarsus®)
Tools have been developed in our unit to calculate the inter-dose AUC (Area Under Curve) of immunosuppressive drugs (ISD) based on a limited number of blood concentrations (i.e., blood samples) using Bayesian methods. Since 2005, we have implemented these tools in an expert system and made them available to the transplant community through our very successful ISBA (Immunosuppressive drugs Bayesian dose Adjustment) website.
Briefly, we first need to develop a population pharmacokinetic model using rich pharmacokinetic (PK) profiles (about 10 samples per patient over the dosing interval). The model developed can then be used for inference of ISD PK parameters in new patients using Bayesian estimation. Bayes' theorem is based on conditional probability: individual PK parameters are estimated based on the known PK parameters in the population (mean and distribution), given the dose and concentrations observed in a patient. Our previous studies have shown that a limited sampling strategy (LSS) based on 3 samples collected within the first 3 hours after drug intake can estimate adequately the interdose AUC of ISD. In the present study, the AUC0-24h and the recommended dose will be calculated using Bayesian estimators previously developed using PK data from the clinical trials run by Veloxis, and proposed to the clinicians via a dedicated website comparable with ISBA.
- Conditions
- Allograft
- Being tested
- switched from Prograf® to Envarsus®
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
switched from Prograf® to Envarsus®Drug
| Study group | Role | What they receive |
|---|---|---|
| DBS (dried blood spots) collection | Experimental | In this study, we make a switch from Prograf® to Envarsus®. Patients will be trained to collect their blood from a finger prick on filter paper. DBS will be done at home, collected on filter paper and mailed by the patients to a centralized laboratory (Department of Pharmacology, Toxicology and Pharmacovigilance at Limoges University Hospital), where tacrolimus concentration will be determined by HPLC-MS/MS Receives: Drug: switched from Prograf® to Envarsus® |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference between the post-switch tacrolimus steady-state AUC0-24h (V4) and the pre-switch AUC0-24h (V2).
The tacrolimus AUC0-24h at V2 (patient on Prograf®) will be calculated by summing the morning and the evening tacrolimus AUC0-12h.
Measured: 3 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Aug 2016 (estimated)
- Study startOct 2016
- Primary completionMar 2020
- Study completionMar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AllograftStudies of the same condition, open and under way.
- More trials run by University Hospital, LimogesThe 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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Enrolment
- 134 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Limoges
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02882828
- Sponsor's protocol ID
- I160015
- Acronym
- ENVARSWITCH
- Status last verified
- Nov 2025
- First submitted
- 19 Aug 2016
- Last updated
- 21 Nov 2025
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Monchaud C, Woillard JB, Crepin S, Tafzi N, Micallef L, Rerolle JP, Dharancy S, Conti F, Choukroun G, Thierry A, Buchler M, Salame E, Garrouste C, Duvoux C, Colosio C, Merville P, Anglicheau D, Etienne I, Saliba F, Mariat C, Debette-Gratien M, Marquet P. Tacrolimus Exposure Before and After a Switch From Twice-Daily Immediate-Release to Once-Daily Prolonged Release Tacrolimus: The ENVARSWITCH Study. Transpl Int. 2023 Aug 1;36:11366. doi: 10.3389/ti.2023.11366. eCollection 2023.
PubMed 37588007
Study at a glance
From the registry record, last updated by the sponsor on 21 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetic Assessment of Tacrolimus Exposure Before and After a Switch From Twice Daily Immediate-release (Prograf®) to Once-daily Prolonged Release Tacrolimus (Envarsus®)
- ClinicalTrials.gov ID
- NCT02882828
- Acronym / sponsor ID
- ENVARSWITCH / I160015
- Conditions
- Allograft
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 134 participants (actual)
- Lead sponsor
- University Hospital, LimogesUniversity, hospital or other
- Study start
- Oct 2016
- Primary completion
- Mar 2020 (actual)
- Study completion
- Mar 2020 (actual)
- First posted
- 30 Aug 2016 (estimated)
- 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.
Tools have been developed in our unit to calculate the inter-dose AUC (Area Under Curve) of immunosuppressive drugs (ISD) based on a limited number of blood concentrations (i.e., blood samples) using Bayesian methods. Since 2005, we have implemented these tools in an expert system and made them available to the transplant community through our very successful ISBA (Immunosuppressive drugs Bayesian dose Adjustment) website.
Briefly, we first need to develop a population pharmacokinetic model using rich pharmacokinetic (PK) profiles (about 10 samples per patient over the dosing interval). The model developed can then be used for inference of ISD PK parameters in new patients using Bayesian estimation. Bayes' theorem is based on conditional probability: individual PK parameters are estimated based on the known PK parameters in the population (mean and distribution), given the dose and concentrations observed in a patient. Our previous studies have shown that a limited sampling strategy (LSS) based on 3 samples collected within the first 3 hours after drug intake can estimate adequately the interdose AUC of ISD. In the present study, the AUC0-24h and the recommended dose will be calculated using Bayesian estimators previously developed using PK data from the clinical trials run by Veloxis, and proposed to the clinicians via a dedicated website comparable with ISBA.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| DBS (dried blood spots) collection | Experimental | Drug: switched from Prograf® to Envarsus®In this study, we make a switch from Prograf® to Envarsus®. Patients will be trained to collect their blood from a finger prick on filter paper. DBS will be done at home, collected on filter paper and mailed by the patients to a centralized laboratory (Department of Pharmacology, Toxicology and Pharmacovigilance at Limoges University Hospital), where tacrolimus concentration will be determined by HPLC-MS/MS |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Adult (≥ 18 year-old) male and female patients
- Recipient of a single kidney or liver allograft
- Patient transplanted for more than 2 weeks and less than 1 year at enrolment
- Patient with stable Prograf® dose, defined by the following criteria:
- Patient for whom the decision is made to switch from Prograf® to Envarsus®
Key exclusion criteria (7 listed)
- Patient presenting any contra-indication to tacrolimus according to the summary of product characteristics (SmPC) of Envarsus®
- Recipient of any transplanted organ other than kidney or liver
- Patient treated by Prograf® for less than 7 days at enrolment
- Patient previously treated by any other investigational agent if it is not stopped at least 7 days prior to enrolment
- Pregnant or lactating woman (based on declaration)
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 |
|---|---|---|
| switched from Prograf® to Envarsus® | Drug | DBS (dried blood spots) collection |
Primary outcome
Difference between the post-switch tacrolimus steady-state AUC0-24h (V4) and the pre-switch AUC0-24h (V2).
Time frame: 3 days
The tacrolimus AUC0-24h at V2 (patient on Prograf®) will be calculated by summing the morning and the evening tacrolimus AUC0-12h.
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 21 Nov 2025.
- Results publication: PubMed 37588007Monchaud C, Woillard JB, Crepin S, Tafzi N, Micallef L, Rerolle JP, Dharancy S, Conti F, Choukroun G, Thierry A, Buchler M, Salame E, Garrouste C, Duvoux C, Colosio C, Merville P, Anglicheau D, Etienne I, Saliba F, Mariat C, Debette-Gratien M, Marquet P. Tacrolimus Exposure Before and After a Switch From Twice-Daily Immediate-Release to Once-Daily Prolonged Release Tacrolimus: The ENVARSWITCH Study. Transpl Int. 2023 Aug 1;36:11366. doi: 10.3389/ti.2023.11366. eCollection 2023.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
9 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 switched from Prograf® to Envarsus® in people with Allograft, run by University Hospital, Limoges at 9 sites in France.
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 10 inclusion and 7 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 21 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in France. 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?
Difference between the post-switch tacrolimus steady-state AUC0-24h (V4) and the pre-switch AUC0-24h (V2). (time frame: 3 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02882828, which also lists 1 linked publication.
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 21 Nov 2025.