Non-invasive Test for Acute Rejection Identification in Heart Transplanted Patients (INNOGRAFTRS001)

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

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.

Study Overview

• Status: Unknown
• Conditions: Acute Rejection of Cardiac Transplant
• Intervention / Treatment: Diagnostic test: INNOGRAFT Heart Suite

Detailed 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.

• Study Type: Observational
• Enrollment (Anticipated): 72

Contacts and Locations

Study Locations

• Italy
  • Pavia, Italy, 27100
    • IRCCS Fondazione Policlinico San Matteo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Heart transplanted consecutive adult patients , who underwent their regular surveillance protocol during the first 3 years post intervention.

Description

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Collaborators and Investigators

• Sponsor: Myway Gentics Srl
• Collaborators: Istituto Di Ricerche Farmacologiche Mario Negri; Fondazione IRCCS Policlinico San Matteo di Pavia
• Investigators: Study Director: Valentina Favalli, PhD, Myway Gentics Srl

Study record dates

Study Major Dates

• Study Start (Actual): February 3, 2020
• Primary Completion (Anticipated): June 1, 2020
• Study Completion (Anticipated): September 1, 2020

Study Registration Dates

• First Submitted: February 15, 2020
• First Submitted That Met QC Criteria: February 17, 2020
• First Posted (Actual): February 18, 2020

Study Record Updates

• Last Update Posted (Actual): February 18, 2020
• Last Update Submitted That Met QC Criteria: February 17, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: cfDNA; liquid biopsy
• Other Study ID Numbers: INNOGRAFTRS001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Statistical aalysisi will be available at the end of the study
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No