Improving Immunosuppressive Therapy in Heart Transplantation

NCT03932539 | Unknown

• 1 other identifier: 15547/2019
• Study Type: observational
• Target: 25
• Locations: 1 country
• Sites: 4

Brief 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. 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.

Conditions

Rejection Heart Transplant; Immunosuppression

Keywords

Immunosuppressive therapy; Tacrolimus; Heart transplantation; Pharmacokinetics; Pharmacogenetics; Acute rejection

Outcome Measures

Primary Outcomes (3)

• 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

  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)

  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

  2 years

Secondary Outcomes (1)

• Pharmacogenetic analysis

  2 years

Study Arms (1)

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.

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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

You may qualify if:

• de-novo heart transplant recipients
• Male and female (18-70 years)
• Receiving TAC in combination with steroids, antiproliferative drugs, Everolimus, Sirolimus.

You may not qualify if:

• 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

Sponsors & Collaborators

• Fondazione IRCCS Policlinico San Matteo di Pavia: lead

Study Sites (4)

Clinical and Experimental Pharmacokinetics Unit

Pavia, 27100, Italy

Location

Clinical Epidemiology and Biometry Unit

Pavia, 27100, Italy

Location

Department of Cardiac Surgery

Pavia, 27100, Italy

Location

Department of Respiratory Diseases - Biochemical and Genetics Lab.

Pavia, 27100, Italy

Location

Study Officials

• Mariadelfina Molinaro, MScBiol

  IRCCS Policlinico San Matteo

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 24, 2019
• First Posted: April 30, 2019
• Study Start: May 14, 2019
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2021
• Last Updated: August 19, 2019

Record last verified: 2019-08

Locations

IT (4)