End Stage Liver Disease3PIGREFNCT01760356
Study of PD/PK/PG Relationships of Tacrolimus and Cyclosporin in Liver Transplant Patients
An observational study of End Stage Liver Disease and Rejection, run by UDA Centro Nacional Hepato-Bilio-Pancreático at 1 site in Uruguay.
Trial summary
To search for suitable pharmacodynamic biomarkers, i.e., with high specificity for calcineurin inhibition and most affected by inter-individual variability, our works aimed at exploring the pharmacodynamics of CNI, the strength and variability of signal translation along the calcineurin pathway, as well as the steps… Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- End Stage Liver Disease, Rejection, Infection
- How many people
- 141 participants
- Where
- 1 siteUruguay
- Study dates
- 1 May 2011to 17 May 2021
- How long will I take part?
- 12 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 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Healthy Volunteers Patients of the Waiting List for Liver Transplantation Liver Transplant recipients on Tacrolimus Liver Transplant Recipients on Cyclosporine Longitudinal Cohort of Patients since their pretransplant condition up 1 year posttransplantation
Who may be able to join
- Healthy volunteers:
- Age: 18 to 70 years.
- Ethnicity: Hispanic, African American.
- Gender: male and female.
- Condition: healthy.
- Informed consent: granted and signed informed consent at the time of inclusion and agreement to comply with all the procedures included in the protocol.
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- Waiting List Patients:
- Age: 18 to 70 years.
- Ethnicity: Hispanic, African American.
- Gender: male and female.
- Being active on the waiting list for liver transplantation
- Informed consent: granted and signed at the time of inclusion and agreement to comply with all the procedures included in the protocol.
- Transplant Patients:
- Age: 18 to 70 years.
- Ethnicity: Hispanic, African American.
- Gender: male and female.
- Drug therapy: cyclosporine or tacrolimus, with or without mycophenolic acid derivatives and/or corticosteroids.
- Informed consent: granted and signed at the time of inclusion and agreement to comply with all the procedures included in the protocol.
Who cannot join
- Healthy volunteers:
- pregnancy
- breastfeeding
- chronic drug treatment
- non healthy
- Waiting List Patients:
Show all 16Show fewer
- Patients with previous transplant.
- Patients with more of one transplanted organ.
- Patients on anticalcineurin drugs.
- Patients with impaired renal function - creatinine clearance ≤ 20 ml/min.
- Transplant Patients:
- Pregnant or breastfeeding.
- Patients with prior retransplantation.
- Patients with more of one transplanted organ.
- Patients with impaired renal function - creatinine clearance ≤ 20 ml/min.
- Everolimus indication at any time during treatment.
Trial locations and contacts
1 site in 1 country.
Uruguay1 site
National Center for Liver Transplantation and Liver Diseases Department, Hospital Central de las Fuerzas Armadas
Montevideo, 11600
About this study
Official title: Study of Pharmacodynamic, Pharmacokinetic and Pharmacogenetic Relationships of Anticalcineurin Drugs: Tacrolimus and Cyclosporin in Liver Transplant Recipients.
To search for suitable pharmacodynamic biomarkers, i.e., with high specificity for calcineurin inhibition and most affected by inter-individual variability, our works aimed at exploring the pharmacodynamics of CNI, the strength and variability of signal translation along the calcineurin pathway, as well as the steps where sources of internal (genetic) or external variability are the most influential.
In order to achieve this, we assessed simultaneously NFAT1 translocation into the nucleus of peripheral blood mononuclear cells (PBMC) (NFTA1 being the main NAFT isoform in resting and activated lymphocytes), the intracellular expression of IL-2 in CD3+, CD4+ and CD8+ T cell subsets and the membrane expression of CD25 (IL-2Rα), a surface marker of T cells activation, in T cells at large. A non-interventional clinical trial was set up in healthy volunteers, patients registered on a liver transplantation waiting list (WLP) and liver transplant recipients (LTR). A different question was addressed in each group: The healthy volunteer study (n=35): explored TAC PD along the calcineurin pathway by exposing PBMC ex-vivo; modelled signal translation along this cascade; examined the interindividual variability of TAC PD parameters; and investigated the sources of the variability observed and their contribution at each step of the calcineurin pathway. Furthermore, it allowed us to evaluate the analytical variability of our techniques as well as the intra-individual variability of TAC PD parameters. WLP (n=19) were enrolled to confirm in patients with liver diseases the results obtained in healthy volunteers, as well as to test the potential influence of their initial disease on the ex-vivo pharmacodynamics of TAC. The aims of the transversal study of LTR on CNI (n=80) were to further explore the interindividual variability in the PD of CNI in realistic clinical conditions, i.e. in situations of residual PD activities under tacrolimus or cyclosporine exposure, and the potential pharmacogenetic (PG) sources of such variability. The (still small) group of liver transplant patients (n=9) enrolled immediately before transplantation and followed-up with serial monitoring along the first year post-transplantation was intended to explore the relationships between CNI PD and clinical responses.
Read the detailed description
The research will be conducted under the rules of Good Clinical Practice, Good Laboratory Practice of the International Conference on Harmonisation (ICH)and the Principles of Declaration of Helsinki.
Groups of study are included once inclusion/exclusion criteria were verified and after written informed consent was given: healthy volunteers, patients of the waiting list for liver transplantation, liver transplant recipients on tacrolimus and cyclosporine and a longitudinal cohort of patients enrolled since the waiting list for transplantation.
From this instance proceed the sampling plan. Considering potential dropouts or withdrawals during the study, the intention is to recruit an additional 10% to compensate for the cohorts, as they allow.
The study design does not suppose applying masking methods, since it is an open study.
All data required in the registration forms will be recorded, however in case of persistent failure, will be properly documented the reasons for the absence. Each instance will merit a particular analysis, dated and signed.
Models could be used to estimate the impact of bias due to potential missing data, and if applicable will be complemented with a sensibility analysis.
Loading data will be conducted electronically. Data will be validated according to the data management plan, jointly defined by the principal investigator and the biostatistician, including freezing and thawing processes.
Pharmacokinetic, pharmacogenetic and pharmacodynamic modeling will be done using R software.
Data back ups will be run everyday, and will be archived on tape and a USB storage drive.
Besides self monitoring procedures, the study may be audited by the health authority (during the course of the study or even when it is completed), to assess compliance with the standards of Good Clinical Practice.
Atypical results if any, will be handled according to the criteria of results outside of specification. If re-analysis of samples will occur, they will be properly documented.
Sample size calculation includes the percentage of occurrence of acute cellular rejection and adverse events, as reported by the National Liver Transplant Program and the possible rates of abandonment or premature retirement of the in study subjects.
Under national rates, will be studied at least 30 healthy volunteers, 50 patients and 12 patients with end stage liver disease enlisted for liver transplantation, with serial follow-up during the first year.
Statistical analysis will be performed according to the principle of "intention to treat", and will be the responsible for at least one specialist in biostatistics.
It will be developed a descriptive analysis of all variables collected. Categorical variables will be expressed in percentages and number of observations. Continuous variables will be expressed as mean and coefficient of variation or median and 25th and 75th percentiles, minimum and maximum. Lof transformations will be held whenever needed.
The variables will be compared between groups according to the patient's original listing (intention to treat). They will be calculated and presented the estimated relative risks and their effect with 95% confidence intervals.
For comparison of categorical variables, it will be used the Chi-square test or Fisher's exact test as appropriate.
For comparison of continuous variables, it will be used the test "t" of Student.
For variables that develop with time, they will be represented by Kaplan-Meier curves and compared using the "log-rank" test. Their relative risk with 95% confidence interval will be calculated.
To identify variables associated with different responses multivariate linear analysis, logistic or Cox proportional will be used.
All analyzes will be performed with hypothesis testing and a 2-tailed significance level of 5%.
The program used will be R. Multivariate analysis will be held corrected according Bonferroni's criteria.
We have established standard operating procedures to describe blood collection instances, biological fluids sampling circuit, evaluation of the candidates to include in the study, verification of the inclusion criteria, monitoring of patients during the study, record of undesirable events and report of adverse drug reactions, terminating tracking.
- Conditions
- End Stage Liver Disease, Rejection, Infection, Malignancy, Toxicity, Diabetes
- Keywords
- Liver transplantation, Calcineurin inhibitors, Pharmacodynamic biomarkers, Calcineurin pathway, Tacrolimus, interindividual variability
- Medical subject headings
- End Stage Liver Disease, Rejection, Psychology, Infections, Neoplasms, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Healthy Volunteers No treatment | This is set as reference a cohort of untreated healthy volunteers, over which will be measured the biomarkers to determine the baseline. Implies PBMC ex-vivo exposure to Tacrolimus prior all cell incubations to study ex-vivo PD in stimulated conditions with mitogens to identify potential genetic sources of interindividual variability in physiological conditions Number proposed 30. | |
| Liver Transplant Patients on Tacrolimus | To explore PD/PG/PK relationships of TAC residual PD activities ex-vivo in stimulated and non-stimulated conditions in liver recipients. The number proposed is 50. | |
| Waiting List for Liver Transplantation | To study the ex-vivo PD response to TAC in stimulated and non-stimulated conditions and the potential genetic sources of PD variability in pathological conditions. The number proposed is 12. | |
| Liver Transplant Patients on Cyclosporine | To explore PD/PG/PK relationships of CsA residual PD activities ex-vivo in stimulated and non-stimulated conditions in liver recipients. The number proposed is 10. | |
| Longitudinal Cohort | Patients form the waiting list for liver transplantation will be enrolled and monitored at different times after transplantation to study the relationships between TAC PD and the clinical responses. The number proposed is 20. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Percentage of expression of CD25High in CD3, CD4 and CD8 T Lymphocytes.
Related to T lymphocyte activation
Measured: All subjects at the inclusion. Patients from the longitudinal cohort: at 0, 30, 90, 180 and 360 days post transplantation.
Pharmacogenetic investigations
Related to the influence of genetic variants in anticalcineurin drug pharmacodynamics
Measured: At the moment of the inclusion for all cohorts.
Anticalcineurin drug concentration through levels
Related to whole blood target calcineurin inhibitor concentration values
Measured: At the moment of the inclusion and at each regular office visit during check up.
Change in Mean Fluorescence Intensity of NFAT1 Nuclear Translocation Inhibition in PMBC nuclei.
Related to calcineruin activation/inhibition (enzyme target of this group of drugs).
Measured: All subjects at the inclusion. Patients from the longitudinal cohort: at 0, 30, 90, 180 and 360 days post transplantation.
Change in the Percentage of expression of IL-2 in CD4 and CD8 subsets of T lymphocytes.
Related to T cell function and the maintenance of T cell response.
Measured: All subjects at the inclusion. Patients from the longitudinal cohort: at 0, 30, 90, 180 and 360 days post transplantation.
Secondary outcomes (9)
Acute Cellular Rejection Mild, Moderate and Severe
Recipients's Immune response to his graft
Measured: Within the year of follow up.
Infection Episodes which requiere anmicrobials treament
Measured: Within the year of follow up
Neurotoxicity to CNIs
Measured: Within the year of follow up
Nephrotoxicity to CNIs
Measured: Within the year of follow up
Malignancies
Measured: Within the year of follow up
Post transplant Diabetes
Measured: Within the year of follow up
Cardiovascular disease, post transplant blood pressure augmentation
Measured: Within the year of follow up
Death
Measured: Within the year of follow up
Post transplant surgical complications
Measured: Within the year of follow up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jan 2013 (estimated)
- Study start1 May 2011
- Primary completion28 Feb 2015
- Study completion17 May 2021
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 End Stage Liver DiseaseStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 141 participants (actual)
- Target duration
- 12 Months
Sponsor and investigators
- Lead sponsor
- UDA Centro Nacional Hepato-Bilio-Pancreático
- Sponsor type
- University, hospital or other
- Collaborators
- INSERM UMR-S850, Limoges, France, University Hospital, Limoges, PEDECIBA, Uruguay, Universidad de la Republica, ANII (Agencia Nacional de Investigación e Innovación), Uruguay, Scientific Cooperation Service, French Embassy, Uruguay, Hospital Central de las Fuerzas Armadas, Uruguay, ECOS Sud Program France-Uruguay, National Center for Liver Transplantation, Uruguay
- Responsible party
- Sponsor
- Investigators
- Ofelia M Noceti, PhD, PharmD, Principal investigator, National Center for Liver Transplantation and Liver Diseases Department, Hospital Central de las Fuerzas ArmadasSolange Gerona, MD, Study chair, National Center for Liver Transplantation and Liver Diseases Department, Hospital Central de las Fuerzas Armadas
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01760356
- Sponsor's protocol ID
- 3PIGREF- 2009 -1165
- Acronym
- 3PIGREF
- Status last verified
- May 2021
- First submitted
- 1 Dec 2012
- Last updated
- 19 May 2021
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: Through scientific publications and congresses
Publications
Noceti O, Pouche L, Esperon P, Lens D, Vital M, Tourino C, Gerona S, Woillard JB, Marquet P. Activity of the Calcineurin Pathway in Patients on the Liver Transplantation Waiting List: Factors of Variability and Response to Tacrolimus Inhibition. Clin Chem. 2017 Nov;63(11):1734-1744. doi: 10.1373/clinchem.2017.272534.
PubMed 29054923
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of Pharmacodynamic, Pharmacokinetic and Pharmacogenetic Relationships of Anticalcineurin Drugs: Tacrolimus and Cyclosporin in Liver Transplant Recipients.
- ClinicalTrials.gov ID
- NCT01760356
- Acronym / sponsor ID
- 3PIGREF / 3PIGREF- 2009 -1165
- Conditions
- End Stage Liver Disease, Rejection, Infection, Malignancy, Toxicity, Diabetes
- Keywords
- Liver transplantation, Calcineurin inhibitors, Pharmacodynamic biomarkers, Calcineurin pathway, Tacrolimus, interindividual variability
- Study type
- Observational
- Recruitment status
- Terminated
- Enrolment
- 141 participants (actual)
- Lead sponsor
- UDA Centro Nacional Hepato-Bilio-PancreáticoUniversity, hospital or other
- Collaborators
- INSERM UMR-S850, Limoges, France, University Hospital, Limoges, PEDECIBA, Uruguay, Universidad de la Republica, ANII (Agencia Nacional de Investigación e Innovación), Uruguay, Scientific Cooperation Service, French Embassy, Uruguay, Hospital Central de las Fuerzas Armadas, Uruguay, ECOS Sud Program France-Uruguay, National Center for Liver Transplantation, Uruguay
- Study start
- 1 May 2011 (actual)
- Primary completion
- 28 Feb 2015 (actual)
- Study completion
- 17 May 2021 (actual)
- First posted
- 4 Jan 2013 (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.
To search for suitable pharmacodynamic biomarkers, i.e., with high specificity for calcineurin inhibition and most affected by inter-individual variability, our works aimed at exploring the pharmacodynamics of CNI, the strength and variability of signal translation along the calcineurin pathway, as well as the steps where sources of internal (genetic) or external variability are the most influential.
In order to achieve this, we assessed simultaneously NFAT1 translocation into the nucleus of peripheral blood mononuclear cells (PBMC) (NFTA1 being the main NAFT isoform in resting and activated lymphocytes), the intracellular expression of IL-2 in CD3+, CD4+ and CD8+ T cell subsets and the membrane expression of CD25 (IL-2Rα), a surface marker of T cells activation, in T cells at large. A non-interventional clinical trial was set up in healthy volunteers, patients registered on a liver transplantation waiting list (WLP) and liver transplant recipients (LTR). A different question was addressed in each group: The healthy volunteer study (n=35): explored TAC PD along the calcineurin pathway by exposing PBMC ex-vivo; modelled signal translation along this cascade; examined the interindividual variability of TAC PD parameters; and investigated the sources of the variability observed and their contribution at each step of the calcineurin pathway. Furthermore, it allowed us to evaluate the analytical variability of our techniques as well as the intra-individual variability of TAC PD parameters. WLP (n=19) were enrolled to confirm in patients with liver diseases the results obtained in healthy volunteers, as well as to test the potential influence of their initial disease on the ex-vivo pharmacodynamics of TAC. The aims of the transversal study of LTR on CNI (n=80) were to further explore the interindividual variability in the PD of CNI in realistic clinical conditions, i.e. in situations of residual PD activities under tacrolimus or cyclosporine exposure, and the potential pharmacogenetic (PG) sources of such variability. The (still small) group of liver transplant patients (n=9) enrolled immediately before transplantation and followed-up with serial monitoring along the first year post-transplantation was intended to explore the relationships between CNI PD and clinical responses.
Detailed description
The research will be conducted under the rules of Good Clinical Practice, Good Laboratory Practice of the International Conference on Harmonisation (ICH)and the Principles of Declaration of Helsinki.
Groups of study are included once inclusion/exclusion criteria were verified and after written informed consent was given: healthy volunteers, patients of the waiting list for liver transplantation, liver transplant recipients on tacrolimus and cyclosporine and a longitudinal cohort of patients enrolled since the waiting list for transplantation.
From this instance proceed the sampling plan. Considering potential dropouts or withdrawals during the study, the intention is to recruit an additional 10% to compensate for the cohorts, as they allow.
The study design does not suppose applying masking methods, since it is an open study.
All data required in the registration forms will be recorded, however in case of persistent failure, will be properly documented the reasons for the absence. Each instance will merit a particular analysis, dated and signed.
Models could be used to estimate the impact of bias due to potential missing data, and if applicable will be complemented with a sensibility analysis.
Loading data will be conducted electronically. Data will be validated according to the data management plan, jointly defined by the principal investigator and the biostatistician, including freezing and thawing processes.
Pharmacokinetic, pharmacogenetic and pharmacodynamic modeling will be done using R software.
Data back ups will be run everyday, and will be archived on tape and a USB storage drive.
Besides self monitoring procedures, the study may be audited by the health authority (during the course of the study or even when it is completed), to assess compliance with the standards of Good Clinical Practice.
Atypical results if any, will be handled according to the criteria of results outside of specification. If re-analysis of samples will occur, they will be properly documented.
Sample size calculation includes the percentage of occurrence of acute cellular rejection and adverse events, as reported by the National Liver Transplant Program and the possible rates of abandonment or premature retirement of the in study subjects.
Under national rates, will be studied at least 30 healthy volunteers, 50 patients and 12 patients with end stage liver disease enlisted for liver transplantation, with serial follow-up during the first year.
Statistical analysis will be performed according to the principle of "intention to treat", and will be the responsible for at least one specialist in biostatistics.
It will be developed a descriptive analysis of all variables collected. Categorical variables will be expressed in percentages and number of observations. Continuous variables will be expressed as mean and coefficient of variation or median and 25th and 75th percentiles, minimum and maximum. Lof transformations will be held whenever needed.
The variables will be compared between groups according to the patient's original listing (intention to treat). They will be calculated and presented the estimated relative risks and their effect with 95% confidence intervals.
For comparison of categorical variables, it will be used the Chi-square test or Fisher's exact test as appropriate.
For comparison of continuous variables, it will be used the test "t" of Student.
For variables that develop with time, they will be represented by Kaplan-Meier curves and compared using the "log-rank" test. Their relative risk with 95% confidence interval will be calculated.
To identify variables associated with different responses multivariate linear analysis, logistic or Cox proportional will be used.
All analyzes will be performed with hypothesis testing and a 2-tailed significance level of 5%.
The program used will be R. Multivariate analysis will be held corrected according Bonferroni's criteria.
We have established standard operating procedures to describe blood collection instances, biological fluids sampling circuit, evaluation of the candidates to include in the study, verification of the inclusion criteria, monitoring of patients during the study, record of undesirable events and report of adverse drug reactions, terminating tracking.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 12 Months
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Healthy Volunteers No treatment | – | –This is set as reference a cohort of untreated healthy volunteers, over which will be measured the biomarkers to determine the baseline. Implies PBMC ex-vivo exposure to Tacrolimus prior all cell incubations to study ex-vivo PD in stimulated conditions with mitogens to identify potential genetic sources of interindividual variability in physiological conditions Number proposed 30. |
| Liver Transplant Patients on Tacrolimus | – | –To explore PD/PG/PK relationships of TAC residual PD activities ex-vivo in stimulated and non-stimulated conditions in liver recipients. The number proposed is 50. |
| Waiting List for Liver Transplantation | – | –To study the ex-vivo PD response to TAC in stimulated and non-stimulated conditions and the potential genetic sources of PD variability in pathological conditions. The number proposed is 12. |
| Liver Transplant Patients on Cyclosporine | – | –To explore PD/PG/PK relationships of CsA residual PD activities ex-vivo in stimulated and non-stimulated conditions in liver recipients. The number proposed is 10. |
| Longitudinal Cohort | – | –Patients form the waiting list for liver transplantation will be enrolled and monitored at different times after transplantation to study the relationships between TAC PD and the clinical responses. The number proposed is 20. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Healthy Volunteers Patients of the Waiting List for Liver Transplantation Liver Transplant recipients on Tacrolimus Liver Transplant Recipients on Cyclosporine Longitudinal Cohort of Patients since their pretransplant condition up 1 year posttransplantation
Key inclusion criteria (18 listed)
- Age: 18 to 70 years.
- Ethnicity: Hispanic, African American.
- Gender: male and female.
- Condition: healthy.
- Informed consent: granted and signed informed consent at the time of inclusion and agreement to comply with all the procedures included in the protocol.
Key exclusion criteria (16 listed)
- pregnancy
- breastfeeding
- chronic drug treatment
- non healthy
- Patients with previous transplant.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Change in Percentage of expression of CD25High in CD3, CD4 and CD8 T Lymphocytes.
Time frame: All subjects at the inclusion. Patients from the longitudinal cohort: at 0, 30, 90, 180 and 360 days post transplantation.
Related to T lymphocyte activation
Pharmacogenetic investigations
Time frame: At the moment of the inclusion for all cohorts.
Related to the influence of genetic variants in anticalcineurin drug pharmacodynamics
Anticalcineurin drug concentration through levels
Time frame: At the moment of the inclusion and at each regular office visit during check up.
Related to whole blood target calcineurin inhibitor concentration values
Change in Mean Fluorescence Intensity of NFAT1 Nuclear Translocation Inhibition in PMBC nuclei.
Time frame: All subjects at the inclusion. Patients from the longitudinal cohort: at 0, 30, 90, 180 and 360 days post transplantation.
Related to calcineruin activation/inhibition (enzyme target of this group of drugs).
Change in the Percentage of expression of IL-2 in CD4 and CD8 subsets of T lymphocytes.
Time frame: All subjects at the inclusion. Patients from the longitudinal cohort: at 0, 30, 90, 180 and 360 days post transplantation.
Related to T cell function and the maintenance of T cell response.
9 secondary outcomes
Acute Cellular Rejection Mild, Moderate and Severe
Time frame: Within the year of follow up.
Infection Episodes which requiere anmicrobials treament
Time frame: Within the year of follow up
Neurotoxicity to CNIs
Time frame: Within the year of follow up
Nephrotoxicity to CNIs
Time frame: Within the year of follow up
Malignancies
Time frame: Within the year of follow up
Post transplant Diabetes
Time frame: Within the year of follow up
Cardiovascular disease, post transplant blood pressure augmentation
Time frame: Within the year of follow up
Death
Time frame: Within the year of follow up
Post transplant surgical complications
Time frame: Within the year of follow up
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2021.
- Derived from this study: PubMed 29054923Noceti O, Pouche L, Esperon P, Lens D, Vital M, Tourino C, Gerona S, Woillard JB, Marquet P. Activity of the Calcineurin Pathway in Patients on the Liver Transplantation Waiting List: Factors of Variability and Response to Tacrolimus Inhibition. Clin Chem. 2017 Nov;63(11):1734-1744. doi: 10.1373/clinchem.2017.272534.
- Individual participant dataSharing planned: Yes. Through scientific publications and congresses
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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.
Ofelia M Noceti, PhD, PharmD principal investigator
National Center for Liver Transplantation and Liver Diseases Department, Hospital Central de las Fuerzas Armadas
Solange Gerona, MD study chair
National Center for Liver Transplantation and Liver Diseases Department, Hospital Central de las Fuerzas Armadas
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 End Stage Liver Disease and Rejection, run by UDA Centro Nacional Hepato-Bilio-Pancreático at 1 site in Uruguay.
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 18 inclusion and 16 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: stopped early, as of the sponsor's last update on 19 May 2021. 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 Uruguay. 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?
The study was stopped early. Results are not available in the source record.
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?
Change in Percentage of expression of CD25High in CD3, CD4 and CD8 T Lymphocytes. (time frame: All subjects at the inclusion. Patients from the longitudinal cohort: at 0, 30, 90, 180 and 360 days post transplantation.). The study lists 5 primary outcomes in all. 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 NCT01760356, 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 19 May 2021.