Tacrolimus and Personalized Therapy to Prevent Acute Rejection Episodes

NCT06338306 | Recruiting

• 1 other identifier: 08073421
• Study Type: observational
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

Heart transplant is the only effective treatment for people with advanced heart failure. Post-transplant pharmacological therapies are of fundamental importance for the survival of individuals after surgery: although considerable progress has been made for combined immunosuppressive therapies, acute cellular and especially non-cellular rejection still represents a great challenge for doctors. To verify the absence of the first signs of acute rejection, the analysis of numerous cardiac biopsies (EMB endomyocardial biopsies) is necessary during the first 12 months following the transplant. Thanks to these scheduled checks, doctors are able to identify the first symptoms of possible chronic rejection and reduce its episodes. Since the analysis of biopsies is also based on subjective interpretations, cases of erroneous conclusions are frequent. The researchers of this study aim not only to analyze the biopsies according to the current best clinical practice, but also to evaluate how much anti-rejection drug is actually contained within them. This is an analysis that is still little used for this type of transplant, which could provide very useful information to doctors. The researchers will focus their attention on one drug in particular, tacrolimus, abbreviated to "TAC". The amount of drug measured in biopsies will be compared with that measured in whole blood samples and in particular blood cells (peripheral blood mononuclear cells: PBMC). The genetic characteristics of each person play an important role in the success of treatment with the drug. To best interpret the results, all participants will be asked to take a blood sample to identify some characteristics of their DNA that could influence the outcome of tacrolimus therapy.

Conditions

Heart Transplant Failure

Keywords

Tacrolimus; Whole Blood; PBMCs; Endomyocardial biopsy; Acute rejection; Therapeutic Drug Monitoring (TDM)

Outcome Measures

Primary Outcomes (3)

• Tacrolimus quantification in an unconventional matrix

  Each biopsy will be weighed immediately after being taken from the transplanted organ during the 5 scheduled follow up visits. Tacrolimus will be extraxcted following a validated and published alalytical procedure, consisting of a combined enzymatic-digestion/mass spectrometry assay (online SPE-LC-MS/MS). Enzymatic tissue digestion followed by a liquid-liquid drug extraction in the same vial of reaction will allow us to avoid both sample loss and contaminations. TAC concentrations will be expressed as "pg TAC/mg biopsy"

  0.5, 1, 3, 6 and 12 months after heart transplantation

• Tacrolimus quantification in PBMCs

  10 mL of peripheral blood will be collected and processed by Fycoll gradient procedure for the PBMCs separation. PBMCs will be isolated and then counted with an automated cell counter. TAC concentration in PBMCs (expressed as "ng/1.000.000 cells") will be detected by a validated online SPE- LC-MS/MS method.

  0.5, 1, 3, 6 and 12 months after heart transplantation

• Tacrolimus quantification in whole blood

  The TAC concentration will be detected in whole blood using an automatic immunoassay system, used daily for routine monitoring. TAC concentration will be expressed as "ng/mL" in whole blood. Therapeutic range: 5-20 ng/mL

  0.5, 1, 3, 6 and 12 months after heart transplantation

Secondary Outcomes (1)

• Genetic profile in heart transplant recipients

  The pharmacogenetic investigation (PGx) will be carried out at enrollment

Study Arms (1)

De novo heart transplant patients

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 (MMF; EC-MPS) or m-TOR inhibitors (Everolimus; Sirolimus).

Drug: Tacrolimus（FK506）

Interventions

Tacrolimus（FK506） DRUG

Prograf

De novo heart transplant patients

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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 (MMF; EC-MPS) or m-TOR inhibitors (Everolimus; Sirolimus).

You may qualify if:

• de novo heart transplant recipient

You may not qualify if:

• Age \< 18 years
• Intolerance to TAC or to some excipient
• Intolerance to glucose
• diabetes mellitus

Sponsors & Collaborators

• Fondazione IRCCS Policlinico San Matteo di Pavia: lead

Study Sites (1)

Fondazione IRCCS Policlinico San Matteo

Pavia, 27100, Italy

RECRUITING

Related Publications (1)

• Molinaro M, Pellegrini C, Cattadori B, De Gregori S. Development and validation of a combined enzymatic-digestion/mass spectrometry assay for Tacrolimus quantitation in cardiac biopsies. J Chromatogr B Analyt Technol Biomed Life Sci. 2020 Sep 1;1152:122215. doi: 10.1016/j.jchromb.2020.122215. Epub 2020 Jun 21.

  PMID: 32615534 BACKGROUND

Central Study Contacts

Alessandra Ferrari

CONTACT

+390382503689; alessandra.ferrari@smatteo.pv.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2024
• First Posted: March 29, 2024
• Study Start: January 7, 2022
• Primary Completion: June 30, 2022
• Study Completion: June 30, 2025
• Last Updated: April 9, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)