Liver TransplantationNCT04444817
Evaluation of the Impact of Tacrolimus-based Immunosuppression on Heidelberg Liver Transplant Cohort (HDTACRO): Study Protocol for an Investigator Initiated, Non-interventional Prospective Study
An observational study of Liver Transplantation, run by University Hospital Heidelberg at 1 site in Germany.
Trial summary
Modern immunosuppression is characterized by a combination of different immunosuppressants. As a result, the dose of the individual substances, and thus also their side effects can be reduced. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Liver Transplantation
- What is being tested?
- Tacrolimus
- How many people
- 100 participants
- Where
- 1 siteGermany
- Study dates
- 22 Nov 2018to 30 Dec 2021
- How long will I take part?
- 6 Months
- Phase
- Observational
- 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 to 60 years
- All sexes
- No healthy volunteers
- Adult
Study population: One hundred Recipients who underwent de novo liver transplant and treated with various oral Tacrolimus-based immunosupresions (Prograf®, Advagraf® and Envarsus®)
Who may be able to join
- 18 < Recipient Age ≤ 60 years old
- Ability to understand and sign an informed consent form
- Operation and immediate post-operative therapy within the Department of General, Visceral and Transplantion Surgery, University Hospital Heidelberg
- De novo liver transplantation until POD 7
- Immunosuppression after liver transplantation based on Tacrolimus
Who cannot join
- Re-transplantation
- Acute infection of the biliary tract, pneumonia or CMV infection
Trial locations and contacts
1 site in 1 country.
Germany1 site, 1 recruiting
- Recruiting
Division of Visceral Transplantation, Department of General, Visceral andTransplantation Surgery, University of Heidelberg
Heidelberg, Baden-Wurttemberg, 69120
Arianeb Mehrabi, MD, 004962215636223, arianeb.mehrabi@med.uni-heidelberg.de
About this study
Modern immunosuppression is characterized by a combination of different immunosuppressants. As a result, the dose of the individual substances, and thus also their side effects can be reduced. Immunosuppression on the basis of low-dose calcineurin inhibitors (CNI) with comparatively low CNI target levels could therefore prevail. Despite all efforts to optimize the treatment regimen after liver transplantation from deceased donors, the amount of medication remains high throughout the postoperative course with CNIs being the main component of immunosuppressive treatment. The main substance used is Tacrolimus in combination with steroids and possibly Mycophenolic acid. Tacrolimus is considered a narrow therapeutic index drug requiring individual dose titration, to achieve a satisfactory balance between maximizing efficacy and minimizing dose-related toxicity. Furthermore, transplanted recipients have to remain to a very demanding medication regimen for a long time. The burden of pills required is associated with decreased adherence, and lack of adherence can lead to rejection and possibly graft loss. The aim of present study is to assess the tough levels and need of doses adaptation in de novo liver transplantation with Tacrolimus in the clinical routine, without any intervention in the treatment regimen.
Read the detailed description
Tacrolimus is considered a narrow therapeutic index drug requiring individual dose titration, to achieve a satisfactory balance between maximizing efficacy and minimizing dose-related toxicity. The pharmacokinetic profile of Tacrolimus is characterized by a high degree of inter- and intraindividual variability. Although it is rapidly absorbed, the bioavailability of Tacrolimus in the twice-daily capsule formulation is low and variable, ranging from 17 to 23%. This could be due to poor water solubility, extensive first pass metabolism, p-glycoprotein-mediated efflux and the ingestion of food. Tacrolimus twice-daily capsules are also associated with a characteristic high peak following dosing, which may be associated with increased toxicity.
Furthermore, transplanted recipients have to remain to a very demanding medication regimen for a long time. The burden of pills required is associated with decreased adherence, and lack of adherence can lead to rejection and possibly graft loss.
The development of once-daily Tacrolimus forms without any change of the form of dissolving has already been shown to increase patients' adherence, while little difference has been demonstrated in the Tacrolimus pharmacokinetic profile. The pharmacokinetic profile of Tacrolimus is characterized by flatter kinetics (i.e., less fluctuation and swing) compared to twice-daily Tacrolimus providing for a balanced concentration-time consistency over 24 hours which can also lead to reduced incidence and/or intensity of drug toxicity-related adverse events. Since the development of LCP-Tacrolimus once-daily tablets, with the use of MeltDose® technology, clinical data have shown lower peak and reduced peak-to-tough fluctuations.
- Conditions
- Liver Transplantation
- Being tested
- Tacrolimus
- Keywords
- Tacrolimus, immunosuppression, Liver transplantation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TacrolimusDrug
Similar to the clinical routine, as soon as a patient is able to swallow and has a sufficient gastrointestinal activity, Tacrolimus-based immunosuppression using Prograf®, Advagraf® or Envarsus® will be started. Furthermore, calcineurin inhibitors-based immunosuppression will be used (initial dose based on the patients' body weight) with the goal of tough levels of 3-7 ng/mL in the first seven days after liver transplantion, depending on immune status and indication for transplantation. Further tough levels will be determined based on factors such as patients' history and indication for liver transplant.
| Study group | Role | What they receive |
|---|---|---|
| Tacrolimus-based immunosuppression | Similar to the clinical routine, as soon as a patient is able to swallow and has a sufficient gastrointestinal activity, Tacrolimus-based immunosuppression using Prograf®, Advagraf® or Envarsus® will be started. Receives: Drug: Tacrolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
The number of required dose adjustments of Tacrolimus formulations used in clinical routine for achieving the target tough level
Measured: Six months
Secondary outcomes (10)
Tacrolimus tough level
Measured: Six months
Tacrolimus dosing
Measured: Six months
Concentration/dose ratio
Measured: Six months
Mean cumulative dose for cost analysis
Measured: Six months
Routine laboratory tests
Measured: Six months
Survival rate
Measured: Six months
The incidence of acute rejection
Measured: Six months
The incidence of re-transplantation
Measured: Six months
Patients' therapy adherence
Measured: Six months
The incidence of infection with need to reduce Immunosuppression
Measured: Six months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2020
- Study start22 Nov 2018
- Primary completion30 Dec 2021 (estimated)
- Study completion30 Dec 2021 (estimated)
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 Liver TransplantationStudies of the same condition, open and under way.
- More trials run by University Hospital HeidelbergThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
- Target duration
- 6 Months
Sponsor and investigators
- Lead sponsor
- University Hospital Heidelberg
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. A. Mehrabi, University Hospital Heidelberg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04444817
- Sponsor's protocol ID
- S-260/2018
- Status last verified
- Jun 2020
- First submitted
- 21 Jun 2020
- Last updated
- 24 Jun 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Khajeh E, Polychronidis G, Ramouz A, Alamdari P, Lemekhova A, Saracevic M, Ali-Hasan-Al-Saegh S, Ghamarnejad O, Majlesara A, Abbasi Dezfouli S, Nickkholgh A, Weiss KH, Rupp C, Mehrabi A, Mieth M. Evaluation of the impact of Tacrolimus-based immunosuppression on Heidelberg liver transplant cohort (HDTACRO): Study protocol for an investigator initiated, non-interventional prospective study. Medicine (Baltimore). 2020 Sep 25;99(39):e22180. doi: 10.1097/MD.0000000000022180.
PubMed 32991411
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Impact of Tacrolimus-based Immunosuppression on Heidelberg Liver Transplant Cohort (HDTACRO): Study Protocol for an Investigator Initiated, Non-interventional Prospective Study
- ClinicalTrials.gov ID
- NCT04444817
- Acronym / sponsor ID
- S-260/2018
- Conditions
- Liver Transplantation
- Keywords
- Tacrolimus, immunosuppression, Liver transplantation
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University Hospital HeidelbergUniversity, hospital or other
- Study start
- 22 Nov 2018 (actual)
- Primary completion
- 30 Dec 2021 (estimated)
- Study completion
- 30 Dec 2021 (estimated)
- First posted
- 24 Jun 2020 (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.
Modern immunosuppression is characterized by a combination of different immunosuppressants. As a result, the dose of the individual substances, and thus also their side effects can be reduced. Immunosuppression on the basis of low-dose calcineurin inhibitors (CNI) with comparatively low CNI target levels could therefore prevail. Despite all efforts to optimize the treatment regimen after liver transplantation from deceased donors, the amount of medication remains high throughout the postoperative course with CNIs being the main component of immunosuppressive treatment. The main substance used is Tacrolimus in combination with steroids and possibly Mycophenolic acid. Tacrolimus is considered a narrow therapeutic index drug requiring individual dose titration, to achieve a satisfactory balance between maximizing efficacy and minimizing dose-related toxicity. Furthermore, transplanted recipients have to remain to a very demanding medication regimen for a long time. The burden of pills required is associated with decreased adherence, and lack of adherence can lead to rejection and possibly graft loss. The aim of present study is to assess the tough levels and need of doses adaptation in de novo liver transplantation with Tacrolimus in the clinical routine, without any intervention in the treatment regimen.
Detailed description
Tacrolimus is considered a narrow therapeutic index drug requiring individual dose titration, to achieve a satisfactory balance between maximizing efficacy and minimizing dose-related toxicity. The pharmacokinetic profile of Tacrolimus is characterized by a high degree of inter- and intraindividual variability. Although it is rapidly absorbed, the bioavailability of Tacrolimus in the twice-daily capsule formulation is low and variable, ranging from 17 to 23%. This could be due to poor water solubility, extensive first pass metabolism, p-glycoprotein-mediated efflux and the ingestion of food. Tacrolimus twice-daily capsules are also associated with a characteristic high peak following dosing, which may be associated with increased toxicity.
Furthermore, transplanted recipients have to remain to a very demanding medication regimen for a long time. The burden of pills required is associated with decreased adherence, and lack of adherence can lead to rejection and possibly graft loss.
The development of once-daily Tacrolimus forms without any change of the form of dissolving has already been shown to increase patients' adherence, while little difference has been demonstrated in the Tacrolimus pharmacokinetic profile. The pharmacokinetic profile of Tacrolimus is characterized by flatter kinetics (i.e., less fluctuation and swing) compared to twice-daily Tacrolimus providing for a balanced concentration-time consistency over 24 hours which can also lead to reduced incidence and/or intensity of drug toxicity-related adverse events. Since the development of LCP-Tacrolimus once-daily tablets, with the use of MeltDose® technology, clinical data have shown lower peak and reduced peak-to-tough fluctuations.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 6 Months
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tacrolimus-based immunosuppression | – | Drug: TacrolimusSimilar to the clinical routine, as soon as a patient is able to swallow and has a sufficient gastrointestinal activity, Tacrolimus-based immunosuppression using Prograf®, Advagraf® or Envarsus® will be started. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- One hundred Recipients who underwent de novo liver transplant and treated with various oral Tacrolimus-based immunosupresions (Prograf®, Advagraf® and Envarsus®)
Key inclusion criteria (5 listed)
- 18 < Recipient Age ≤ 60 years old
- Ability to understand and sign an informed consent form
- Operation and immediate post-operative therapy within the Department of General, Visceral and Transplantion Surgery, University Hospital Heidelberg
- De novo liver transplantation until POD 7
- Immunosuppression after liver transplantation based on Tacrolimus
Key exclusion criteria (2 listed)
- Re-transplantation
- Acute infection of the biliary tract, pneumonia or CMV infection
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 |
|---|---|---|
| TacrolimusSimilar to the clinical routine, as soon as a patient is able to swallow and has a sufficient gastrointestinal activity, Tacrolimus-based immunosuppression using Prograf®, Advagraf® or Envarsus® will be started. Furthermore, calcineurin inhibitors-based immunosuppression will be used (initial dose based on the patients' body weight) with the goal of tough levels of 3-7 ng/mL in the first seven days after liver transplantion, depending on immune status and indication for transplantation. Further tough levels will be determined based on factors such as patients' history and indication for liver transplant. | Drug | Tacrolimus-based immunosuppression |
Primary outcome
The number of required dose adjustments of Tacrolimus formulations used in clinical routine for achieving the target tough level
Time frame: Six months
10 secondary outcomes
Tacrolimus tough level
Time frame: Six months
Tacrolimus dosing
Time frame: Six months
Concentration/dose ratio
Time frame: Six months
Mean cumulative dose for cost analysis
Time frame: Six months
Routine laboratory tests
Time frame: Six months
Survival rate
Time frame: Six months
The incidence of acute rejection
Time frame: Six months
The incidence of re-transplantation
Time frame: Six months
Patients' therapy adherence
Time frame: Six months
The incidence of infection with need to reduce Immunosuppression
Time frame: Six months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2020.
- Derived from this study: PubMed 32991411Khajeh E, Polychronidis G, Ramouz A, Alamdari P, Lemekhova A, Saracevic M, Ali-Hasan-Al-Saegh S, Ghamarnejad O, Majlesara A, Abbasi Dezfouli S, Nickkholgh A, Weiss KH, Rupp C, Mehrabi A, Mieth M. Evaluation of the impact of Tacrolimus-based immunosuppression on Heidelberg liver transplant cohort (HDTACRO): Study protocol for an investigator initiated, non-interventional prospective study. Medicine (Baltimore). 2020 Sep 25;99(39):e22180. doi: 10.1097/MD.0000000000022180.
- Individual participant dataSharing planned: Undecided
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Liver Transplantation, run by University Hospital Heidelberg at 1 site in Germany.
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 5 inclusion and 2 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: status not confirmed, as of the sponsor's last update on 24 Jun 2020. 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 Germany. 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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Arianeb Mehrabi, MD (004962215636223, arianeb.mehrabi@med.uni-heidelberg.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The number of required dose adjustments of Tacrolimus formulations used in clinical routine for achieving the target tough level (time frame: Six months). 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 NCT04444817, 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 24 Jun 2020.