Non-invasive Test for Acute Rejection Identification in Heart Transplanted Patients

Acute Rejection of Cardiac Transplant Clinical Trial

— INNOGRAFTRS001  

Official title:

Non-invasive Test for Acute Rejection Identification in Heart Transplanted Patients: a Pilot Retrospective Study

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04274712
• Other study ID #: INNOGRAFTRS001
• Status: Enrolling by invitation
• Start date: February 3, 2020
• Est. completion date: September 2020

Study information

• Verified date: February 2020
• Source: Myway Gentics Srl
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Aim of the study is to test INNOGRAFT Heart Suite in a clinical setting, using a previously collected set of plasma samples from patients who underwent heart transplant and routinely or symptoms-based surveillance during the period 2016- 2019.

Description:

Aim of the study is to test INNOGRAFT Heart Suite in a clinical setting, using a previously collected set of plasma samples from patients who underwent heart transplant and routinely or symptoms-based surveillance during the period 2016- 2019.

1. Primary end-point

• To evaluate specificity and sensitivity of INNOGRAFT Heart Suite in identifying transplant rejection, using blood samples collected from heart transplanted patients during the same day of endomyocardial biopsy (EMB) using the histological study of EMB specimen as reference technique.

We will evaluate:

1. Presence of rejection (Yes/No),

2. Correct classification of rejection according to ISHLT 2004 guidelines. Rejection will be considered Yes if ISHLT 2004 grading is >1R. We chose ISHLT scale because it has been previously used in studies aimed at sensitivity assessment of other techniques (Deng et al. 2006) and because changes of therapeutic protocol are usually considered in presence of rejection grade higher than 2R.

2. Secondary end-points

• To evaluate the accuracy of INNOGRAFT Heart Suite in discriminating between the classes of rejection according to ISHLT 2004 guidelines using histological study of heart samples from EMB as reference technique

• To look for potential clinical modifiers of cfDNA levels, as quantitatively determined through INNOGRAFT Heart Suite, for every given rejection class. Expected modifiers are inflammatory states not related to rejection and infections. We will also consider the influence of other factors such as gender, age, pregnancy, comorbidities such as other organ failure, diabetes, cancer.

• To find if a correlation between basal donor cfDNA levels, as quantitatively determined through INNOGRAFT Heart Suite on blood samples routinely collected for surveillance or symptoms-based surveillance, and clinical outcomes exists. Clinical outcome considered will be rejection, arrythmias, graft failure, hospitalization, death.

• To find if a correlation between donor cfDNA levels, as quantitatively determined through INNOGRAFT Heart Suite on blood samples routinely collected for surveillance or symptoms-based surveillance, and parameters of cardiac function obtained through right heart catheterization exists. Cardiac catheterization will measure cardiac index, left atrium wedge, right ventricle pressure, pulmonary artery avarage pressure.

• To find if a correlation between donor cfDNA levels, as quantitatively determined through INNOGRAFT Heart Suite on blood samples routinely collected for surveillance or symptoms-based surveillance, and blood levels of calcineurin inhibitor/proliferation inhibitor (in therapeutic range/outside therapeutic range) exists in each patient and between patients. Calcineurin inhibitor, proliferation inhibitor and steroids are routine therapy for patients who underwent heart transplant. Blood levels are routinely measured in patient treated with calcineurin inhibitor or proliferation inhibitor protocols. The aim is to identify through cfDNA measure, the correct patient-specific level of immunosuppression.

• To find if differences in basal donor cfDNA levels, as quantitatively determined through INNOGRAFT Heart Suite on blood samples routinely collected for surveillance or symptoms-based surveillance, between rATG-treated and rATG-untreated patients exist. rATG is intended as induction therapy protocol before heart transplant.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 72
• Est. completion date: September 2020
• Est. primary completion date: June 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

To be eligible for the study, patients must fulfill all the following inclusion criteria.

1. Age=18 years;

2. Heart transplanted during 2016-2019 and under surveillance for preventing acute rejection;

3. Heart transplanted before 2016 but undergoing routinely or symptom-based surveillance for preventing acute rejection;

4. Signed written informed consent for reuse of biosamples for research purposes; OR Signed written informed consent for study partecipation;

5. Underwent at least 1 blood sampling at the same time of the EMB;

6. Clinical data collected during at least 1 surveillance visit (same time of blood sampling and EMB) available;

7. Availability of EMB readings for EMB performed at the same time of blood sampling.

Exclusion Criteria:

1. They were subjected to re-transplantation

2. They were subjected to multi-organ transplantation

Related Conditions & MeSH terms

• Acute Rejection of Cardiac Transplant

Intervention

Diagnostic Test:
• INNOGRAFT Heart Suite
Liquid biopsy to identify acute rejection

Locations

Country	Name	City	State
Italy	IRCCS Fondazione Policlinico San Matteo	Pavia

Sponsors (3)

Lead Sponsor	Collaborator
Myway Gentics Srl	Istituto Di Ricerche Farmacologiche Mario Negri, Policlinico San Matteo Pavia Fondazione IRCCS

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Comparison with gold standard: endomyocardial biopsy	To evaluate specificity and sensitivity of INNOGRAFT Heart Suite in identifying transplant rejection, using blood samples collected from heart transplanted patients during the same day of endomyocardial biopsy (EMB) using the histological study of EMB specimen as reference technique.	6 months
Secondary	Comparison with ISHLT classification	• To evaluate the accuracy of INNOGRAFT Heart Suite in discriminating between the classes of rejection according to ISHLT 2004 guidelines using histological study of heart samples from EMB as reference technique	6 months
Secondary	cfDNA modifiers	• To look for potential clinical modifiers of cfDNA levels, as quantitatively determined through INNOGRAFT Heart Suite, for every given rejection class	6 months