Rejection Heart TransplantNCT03932539
Improving Immunosuppressive Therapy in Heart Transplantation
An observational study of Rejection Heart Transplant and Immunosuppression, run by Fondazione IRCCS Policlinico San Matteo di Pavia at 4 sites in Italy.
Trial summary
Cardiac allograft rejection (CAR) occurs in 30% to 40% of transplant recipients within the first year post-transplant, and carries an increased risk of both acute graft failure and reduced graft longevity. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Rejection Heart Transplant, Immunosuppression
- How many people
- 25 participants
- Where
- 4 sitesItaly
- Study dates
- 14 May 2019to Dec 2021
- 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
- No healthy volunteers
- Adult, Older adult
Study population: If no contraindications will be observed, and the patient will be able to tolerate the administration of the study drug, the patients will be enrolled within the 5th post-transplant day. In the case of impossibility to administer the drug within that period, the patient will not have access to the study
Who may be able to join
- de-novo heart transplant recipients
- Male and female (18-70 years)
- Receiving TAC in combination with steroids, antiproliferative drugs, Everolimus, Sirolimus.
Who cannot join
- Age < 18 years
- Intolerance of the drug object of the present study (Tacrolimus) or at any of the excipients contained therein
- Intolerance to glucose
- Diabetes mellitus
Trial locations and contacts
4 sites in 1 country.
Italy4 sites
Clinical and Experimental Pharmacokinetics Unit
Pavia, 27100
Clinical Epidemiology and Biometry Unit
Pavia, 27100
Department of Cardiac Surgery
Pavia, 27100
Department of Respiratory Diseases - Biochemical and Genetics Lab.
Pavia, 27100
About this study
Official title: New Strategies to Improve Immunosuppressive Therapy Management in Heart Transplantation: a Pilot Study
Cardiac allograft rejection (CAR) occurs in 30% to 40% of transplant recipients within the first year post-transplant, and carries an increased risk of both acute graft failure and reduced graft longevity. Because of the high morbidity of CAR when diagnosed after symptoms develop, surveillance endomyocardial biopsy (EMB) has been included in heart transplantation guidelines since 1990. Although EMB is the established gold standard for the diagnosis of CAR, the clinical utility of EMB using standard hematoxylin and eosin (H\&E) histologic analysis is limited by marked inter-observer variability and significant discordance between the histologic grade and clinical impression of CAR severity.
On the other hand, Tacrolimus (TAC), one of the most important immunosuppressant drug and widely used for the prevention of rejection after solid organ transplantation (SOT), is considered a critical dose drug: too low exposure to TAC may result in under-immunosuppression and acute rejection, whereas overexposure puts patients at risk for toxicity. Tac concentrations, in whole-blood, are considered therapeutic when maintained in the range 5 and 20 ng/mL. In addition to being highly variable inter-individually, TAC pharmacokinetics can also be variable within individual patients.
Although in recent years significant decrease of rejection post SOT has been observed, there is space for further modulation of immunosuppressive therapy, in order to reduce the most common adverse side effects (nephrotoxicity, diabetes, osteoporosis, cardiovascular disease, infections and malignancies), to improve the patients quality of life and to better individualize their therapies. Tac. Unfortunately, a clear correlation between TAC whole blood concentration and acute rejection risk has not yet been defined.
Read the detailed description
Monocentric and Observational Study
- Longitudinal Prospective
The study considers the collection of the following samples:
- a single whole blood sample, 3-5 mL in EDTA for Pharmacogenetics,
- 10 mL whole blood sample in lithium-heparin for Tac quantification in PBMC collected at each time-point scheduled for routine follow-up visits: day +15 and month 1, 3, 6, 12 post transplant
- About 1 mg cardiac tissue samples (from cardiac biopsies), collected by standard procedure adopted at the Transplant Center of CardiacSurgery at each time-point scheduled for routine follow-up visits: day +15 and month 1, 3, 6, 12 post transplant
Each blood sample and biopsy specimen will be identified and labeled with an alphanumeric code, whose decoding matrix will be kept by dedicated personnel at the U.O.C. Cardiac Surgery, Department of Intensive Medicine.
In general, each patient will be defined as "TAC + progressive enrollment number" (example: TAC1, TAC2, TAC3 ...).
Each sample sent to the laboratories for the analyzes in the different matrices and for the different activities foreseen by the protocol (measurements of tacrolimus and pharmacogenetic concentrations) must always contain the identification code assigned to the patient followed by the type of analysis + sampling time. For example, patient collection # 2 for tacrolimus assay to be performed in PBMC, whole blood and EMB at month 3, will be identified as:
TAC2-PBMC-M3 TAC2-WB-M3 TAC2-BEM-M3
The storage of the codes that will allow the patients' identification will be kept by dr. Carlo Pellegrini and dr. Barbara Cattadori (U.O.C. Cardiosurgery).
All samples will be investigated within the Foundation: blood samples for the quantification of Tacrolimus in blood mononuclear cells (PBMC) and in whole blood will be transferred to the Clinical and Experimental Pharmacokinetic Laboratory. Blood samples for pharmacogenetic investigations will be transferred to the Biochemical and Genetic Laboratory of Respiratory Diseases.
The proponents of the study will keep any residual samples at the investigations planned by the study in a safe place with limited access, ie in a freezer -80 °C located in a locked room (room n.11a, Lab Clinical and Experimental Pharmacokinetics, Pavilion 13). These samples can be used for scientific purposes directly related to those of the main study
- Conditions
- Rejection Heart Transplant, Immunosuppression
- Keywords
- Immunosuppressive therapy, Tacrolimus, Heart transplantation, Pharmacokinetics, Pharmacogenetics, Acute rejection
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 |
|---|---|---|
| Twenty-five de-novo heart transplant recipients | Twenty-five de-novo heart transplant recipients will be enrolled, male and female, aging 18-70 years, receiving TAC in combination with steroids and antiproliferative drugs, either Everolimus or Sirolimus. |
What is being measured
The primary outcome is the main question the study is designed to answer.
TAC concentration in whole blood
To detect if a correlation exists between the concentration of tacrolimus in whole blood and the acute transplanted heart rejection.
TAC concentration in whole-blood samples will be measured in ng/mL
Measured: 2 years
TAC concentration in peripheral blood mononuclear cell (PBMC)
To detect if a correlation exists between the concentration of tacrolimus in PBMC and the acute transplanted heart rejection.
TAC concentration will be measured in PBMC (pg/million of cells)
Measured: 2 years
TAC concentration in endomyocardial biopsy (EMB)
To detect if a correlation exists between the concentration of tacrolimus in EMB and the acute transplanted heart rejection.
TAC concentration will be measured in pg/mg of biopsy
Measured: 2 years
Secondary outcomes (1)
Pharmacogenetic analysis
Different single nucleotide polymorphisms (SNPs) will be analyzed in ABCB1 (P-gp) and CYP3A4/CYP3A5 genes
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2019
- Study start14 May 2019
- Primary completionDec 2020 (estimated)
- Study completionDec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rejection Heart TransplantStudies of the same condition, open and under way.
- More trials run by Fondazione IRCCS Policlinico San Matteo di PaviaThe 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
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fondazione IRCCS Policlinico San Matteo di Pavia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mariadelfina Molinaro, Fondazione IRCCS Policlinico San Matteo di Pavia
- Investigators
- Mariadelfina Molinaro, MScBiol, Principal investigator, IRCCS Policlinico San Matteo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03932539
- Sponsor's protocol ID
- 15547/2019
- Status last verified
- Aug 2019
- First submitted
- 24 Apr 2019
- Last updated
- 19 Aug 2019
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- New Strategies to Improve Immunosuppressive Therapy Management in Heart Transplantation: a Pilot Study
- ClinicalTrials.gov ID
- NCT03932539
- Acronym / sponsor ID
- 15547/2019
- Conditions
- Rejection Heart Transplant, Immunosuppression
- Keywords
- Immunosuppressive therapy, Tacrolimus, Heart transplantation, Pharmacokinetics, Pharmacogenetics, Acute rejection
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- Fondazione IRCCS Policlinico San Matteo di PaviaUniversity, hospital or other
- Study start
- 14 May 2019 (actual)
- Primary completion
- Dec 2020 (estimated)
- Study completion
- Dec 2021 (estimated)
- First posted
- 30 Apr 2019 (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.
Cardiac allograft rejection (CAR) occurs in 30% to 40% of transplant recipients within the first year post-transplant, and carries an increased risk of both acute graft failure and reduced graft longevity. Because of the high morbidity of CAR when diagnosed after symptoms develop, surveillance endomyocardial biopsy (EMB) has been included in heart transplantation guidelines since 1990. Although EMB is the established gold standard for the diagnosis of CAR, the clinical utility of EMB using standard hematoxylin and eosin (H\&E) histologic analysis is limited by marked inter-observer variability and significant discordance between the histologic grade and clinical impression of CAR severity.
On the other hand, Tacrolimus (TAC), one of the most important immunosuppressant drug and widely used for the prevention of rejection after solid organ transplantation (SOT), is considered a critical dose drug: too low exposure to TAC may result in under-immunosuppression and acute rejection, whereas overexposure puts patients at risk for toxicity. Tac concentrations, in whole-blood, are considered therapeutic when maintained in the range 5 and 20 ng/mL. In addition to being highly variable inter-individually, TAC pharmacokinetics can also be variable within individual patients.
Although in recent years significant decrease of rejection post SOT has been observed, there is space for further modulation of immunosuppressive therapy, in order to reduce the most common adverse side effects (nephrotoxicity, diabetes, osteoporosis, cardiovascular disease, infections and malignancies), to improve the patients quality of life and to better individualize their therapies. Tac. Unfortunately, a clear correlation between TAC whole blood concentration and acute rejection risk has not yet been defined.
Detailed description
Monocentric and Observational Study
- Longitudinal Prospective
The study considers the collection of the following samples:
- a single whole blood sample, 3-5 mL in EDTA for Pharmacogenetics,
- 10 mL whole blood sample in lithium-heparin for Tac quantification in PBMC collected at each time-point scheduled for routine follow-up visits: day +15 and month 1, 3, 6, 12 post transplant
- About 1 mg cardiac tissue samples (from cardiac biopsies), collected by standard procedure adopted at the Transplant Center of CardiacSurgery at each time-point scheduled for routine follow-up visits: day +15 and month 1, 3, 6, 12 post transplant
Each blood sample and biopsy specimen will be identified and labeled with an alphanumeric code, whose decoding matrix will be kept by dedicated personnel at the U.O.C. Cardiac Surgery, Department of Intensive Medicine.
In general, each patient will be defined as "TAC + progressive enrollment number" (example: TAC1, TAC2, TAC3 ...).
Each sample sent to the laboratories for the analyzes in the different matrices and for the different activities foreseen by the protocol (measurements of tacrolimus and pharmacogenetic concentrations) must always contain the identification code assigned to the patient followed by the type of analysis + sampling time. For example, patient collection # 2 for tacrolimus assay to be performed in PBMC, whole blood and EMB at month 3, will be identified as:
TAC2-PBMC-M3 TAC2-WB-M3 TAC2-BEM-M3
The storage of the codes that will allow the patients' identification will be kept by dr. Carlo Pellegrini and dr. Barbara Cattadori (U.O.C. Cardiosurgery).
All samples will be investigated within the Foundation: blood samples for the quantification of Tacrolimus in blood mononuclear cells (PBMC) and in whole blood will be transferred to the Clinical and Experimental Pharmacokinetic Laboratory. Blood samples for pharmacogenetic investigations will be transferred to the Biochemical and Genetic Laboratory of Respiratory Diseases.
The proponents of the study will keep any residual samples at the investigations planned by the study in a safe place with limited access, ie in a freezer -80 °C located in a locked room (room n.11a, Lab Clinical and Experimental Pharmacokinetics, Pavilion 13). These samples can be used for scientific purposes directly related to those of the main study
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Twenty-five de-novo heart transplant recipients | – | –Twenty-five de-novo heart transplant recipients will be enrolled, male and female, aging 18-70 years, receiving TAC in combination with steroids and antiproliferative drugs, either Everolimus or Sirolimus. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- If no contraindications will be observed, and the patient will be able to tolerate the administration of the study drug, the patients will be enrolled within the 5th post-transplant day. In the case of impossibility to administer the drug within that period, the patient will not have access to the study
Key inclusion criteria (3 listed)
- de-novo heart transplant recipients
- Male and female (18-70 years)
- Receiving TAC in combination with steroids, antiproliferative drugs, Everolimus, Sirolimus.
Key exclusion criteria (4 listed)
- Age < 18 years
- Intolerance of the drug object of the present study (Tacrolimus) or at any of the excipients contained therein
- Intolerance to glucose
- Diabetes mellitus
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
TAC concentration in whole blood
Time frame: 2 years
To detect if a correlation exists between the concentration of tacrolimus in whole blood and the acute transplanted heart rejection. TAC concentration in whole-blood samples will be measured in ng/mL
TAC concentration in peripheral blood mononuclear cell (PBMC)
Time frame: 2 years
To detect if a correlation exists between the concentration of tacrolimus in PBMC and the acute transplanted heart rejection. TAC concentration will be measured in PBMC (pg/million of cells)
TAC concentration in endomyocardial biopsy (EMB)
Time frame: 2 years
To detect if a correlation exists between the concentration of tacrolimus in EMB and the acute transplanted heart rejection. TAC concentration will be measured in pg/mg of biopsy
1 secondary outcome
Pharmacogenetic analysis
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2019.
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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.
Mariadelfina Molinaro, MScBiol principal investigator
IRCCS Policlinico San Matteo
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Rejection Heart Transplant and Immunosuppression, run by Fondazione IRCCS Policlinico San Matteo di Pavia at 4 sites in Italy.
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 3 inclusion and 4 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 19 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Italy. 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?
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?
TAC concentration in whole blood (time frame: 2 years). The study lists 3 primary outcomes in all. 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 19 Aug 2019.