## Protocol Section
### Identification Module
**NCT ID:** NCT05268679

**Acronym:** COVHEART

**Brief Title:** Covid-19 Vaccine Response in Heart Transplant Recipients

**Official Title:** Study of the Humoral and Cellular Response to Vaccines Against SARS-CoV-2 in Heart Transplant Recipients

#### Organization Study ID Info
**ID:** APHP211456
#### Organization
**Class:** OTHER
**Full Name:** Assistance Publique - Hôpitaux de Paris
### Status Module
#### Completion Date
**Date:** 2022-11-30

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-01-03

**Type:** ACTUAL

**Last Update Submit Date:** 2023-12-30

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2022-11-30

**Type:** ACTUAL

#### Start Date
**Date:** 2022-03-07

**Type:** ACTUAL

**Status Verified Date:** 2023-12

#### Study First Post Date
**Date:** 2022-03-07
**Type:** ACTUAL
**Study First Submit Date:** 2022-03-04
**Study First Submit QC Date:** 2022-03-04
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Assistance Publique - Hôpitaux de Paris

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** Clinical studies indicate a decrease in vaccine efficacy in certain immunocompromised populations (kidney transplant recipients, patients undergoing chemotherapy). It was recently reported that only 18% to 49% of heart transplant recipients developed antibodies after 2 doses of BNT162b2 vaccine. Following the published results, it is currently recommended to use 3 doses in organ transplant recipients who have not contracted COVID-19 and 2 doses in those who have been infected. The effectiveness of this strategy is not yet sufficiently evaluated in heart transplant recipients. Moreover, the factors associated with the humoral and cellular response, the kinetics and durability of the humoral response, the occurrence of the cellular immune response and the tolerance of the vaccine are not well known in this population.

To provide answers to these different questions, we set ourselves the objective of evaluating the humoral and cellular response to messenger RNA (mRNA) vaccines in heart transplant recipients followed at Bichat Hospital.

**Detailed Description:** In order to evaluate the effectiveness and safety of currently adopted vaccination strategies in heart transplant recipients we intend to study the humoral and cellular responses to SARS-CoV-2 mRNA vaccines in heart transplant recipients followed at Bichat Hospital.

All heart transplant recipients followed at Bichat Hospital will be invited to participate in this research.

The vaccination schedule was 3 doses for the seronegative patients without documented infection, and 2 doses for patients who were seropositive or had a positive Reverse Transcriptase - Polymerase Chain Reaction (RT-PCR) test for SARS-CoV-2. Most patients were vaccinated at Bichat Hospital. Their vaccination schedule will be recovered. Some patients refused vaccination.

Since the beginning of 2020, the transplant patients have benefited from systematic serological tests and RT-PCR testing of nasopharyngeal swabs in the event of symptoms suggestive of SARS-CoV-2 infection as part of routine care. The results of these tests will be retrieved from medical records retrospectively in order to investigate the kinetics and durability of the humoral response. Demographic and clinical data will be collected to determine the factors associated with vaccine response.

In addition, a whole blood sample will be drawn at inclusion in order to evaluate cellular response. The patients will be also asked to answer a questionnaire regarding vaccine tolerance.

The effectiveness of vaccination program will be assessed after 6-month follow-up based on the occurrence of SARS-CoV-2 infection, unscheduled medical consultation or hospitalization.

### Conditions Module

**Conditions:**

- Heart Transplantation

- COVID-19 Virus Infection

- COVID-19 Vaccine

**Keywords:**

- Heart transplant recipients

- Covid-19 virus infection

- SARS-CoV-2 vaccine

- Vaccine Effectiveness

- Humoral immune response

- Cellular Immune Response

### Design Module

#### Design Info

**Observational Model:** COHORT

**Time Perspective:** OTHER

#### Enrollment Info

**Count:** 190

**Type:** ACTUAL

**Study Type:** OBSERVATIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Heart transplant recipients followed at Bichat Hospital and who were offered vaccination against SARS-CoV-2, regardless of whether they agreed to be vaccinated or not.

**Intervention Names:**

- Other: Biospecimen Collection

- Other: Questionnaire

- Other: Electronic Health Record Review

**Label:** Heart transplant recipients

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Heart transplant recipients

**Description:** A blood of a sample of 2 x 7 mL will be collected for the analysis of the anti-SARS-CoV-2 T-cell response during a scheduled check-up as part of their routine follow-up

**Name:** Biospecimen Collection

**Type:** OTHER

#### Intervention 2

**Arm Group Labels:**

- Heart transplant recipients

**Description:** Patients who have received SARS-CoV-2 vaccination will be asked to complete the Vaccine tolerance questionnaire

**Name:** Questionnaire

**Type:** OTHER

#### Intervention 3

**Arm Group Labels:**

- Heart transplant recipients

**Description:** For heart transplant recipients who were offered vaccination against SARS-CoV-2 medical records will be reviewed retrospectively.

**Name:** Electronic Health Record Review

**Type:** OTHER

### Outcomes Module

#### Primary Outcomes

**Description:** Anti-SARS-CoV-2 neutralizing antibody levels over time, with quantification of immunoglobulin G (IgG) directed against the Receptor Binding Domain (RBD) of the Spike (S) protein

**Measure:** Anti-SARS-CoV-2 neutralizing antibody levels

**Time Frame:** Change from baseline to month 6

**Description:** Search for memory T lymphocytes specific to SARS-CoV-2 using an Elispot interferon γ test during the inclusion visit

**Measure:** Efficacy of COVID-19 Vaccines against SARS-CoV-2 infection

**Time Frame:** Day 0

#### Secondary Outcomes

**Description:** Proportion of vaccinated heart transplant recipients having had an infection documented by RT-PCR and a serious infection requiring hospitalisation

**Measure:** Efficacy of COVID-19 vaccines against SARS-CoV-2 infection

**Time Frame:** Month 6

**Description:** Patients will be asked to complete the Vaccine tolerance questionnaire where they will asses and evaluate their symptoms. These will include Diffuse muscle pain (on a scale of 10)/ Headache (on a scale of 10)/ Digestive disorders/ Skin rash/ Pain at the injection site (on a scale of 10)/ Fever/ Fatigue/ Other. Lower scores for all symptoms would indicate a better tolerance.

**Measure:** Safety of COVID-19 vaccines

**Time Frame:** Day 0

**Description:** Change in SARS-CoV-2 Antibody Concentrations following mRNA COVID-19 vaccine series

**Measure:** Kinetics of the humoral response

**Time Frame:** Change from baseline to month 6

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Heart transplant patients followed at Bichat Hospital
* Aged 18 or older
* Informed and having expressed their non-objection to participation in this research
* Able to give their agreement

Exclusion Criteria:

* Minors
* Heart transplant recipients who have expressed their opposition to their participation
* Legally protected adult
* Persons under the State Medical Assistance (AME)

**Minimum Age:** 18 Years

**Sampling Method:** NON_PROBABILITY_SAMPLE

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

**Study Population:** Heart transplant recipients followed at Bichat Hospital and who were offered vaccination against SARS-CoV-2, regardless of whether they agreed to be vaccinated or not.

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Paris

**Country:** France

**Facility:** AP-HP, Bichat-Claude Bernard Hospital

**Zip:** 75018

#### Overall Officials

**Official 1:**

**Affiliation:** AP-HP, Bichat-Claude Bernard Hospital

**Name:** Richard DORENT, MD

**Role:** PRINCIPAL_INVESTIGATOR

### References Module

#### References

**Citation:** Peled Y, Ram E, Lavee J, Sternik L, Segev A, Wieder-Finesod A, Mandelboim M, Indenbaum V, Levy I, Raanani E, Lustig Y, Rahav G. BNT162b2 vaccination in heart transplant recipients: Clinical experience and antibody response. J Heart Lung Transplant. 2021 Aug;40(8):759-762. doi: 10.1016/j.healun.2021.04.003. Epub 2021 Apr 21.

**PMID:** 34034958

**Citation:** Itzhaki Ben Zadok O, Shaul AA, Ben-Avraham B, Yaari V, Ben Zvi H, Shostak Y, Pertzov B, Eliakim-Raz N, Abed G, Abuhazira M, Barac YD, Mats I, Kramer MR, Aravot D, Kornowski R, Ben-Gal T. Immunogenicity of the BNT162b2 mRNA vaccine in heart transplant recipients - a prospective cohort study. Eur J Heart Fail. 2021 Sep;23(9):1555-1559. doi: 10.1002/ejhf.2199. Epub 2021 May 14.

**PMID:** 33963635

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000007239

- Term: Infections

- ID: D000011024

- Term: Pneumonia, Viral

- ID: D000011014

- Term: Pneumonia

- ID: D000012141

- Term: Respiratory Tract Infections

- ID: D000018352

- Term: Coronavirus Infections

- ID: D000003333

- Term: Coronaviridae Infections

- ID: D000030341

- Term: Nidovirales Infections

- ID: D000012327

- Term: RNA Virus Infections

- ID: D000008171

- Term: Lung Diseases

- ID: D000012140

- Term: Respiratory Tract Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC01

- Name: Infections

- Abbrev: BC08

- Name: Respiratory Tract (Lung and Bronchial) Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

### Condition Browse Module - Browse Leaves

- ID: M2561

- Name: COVID-19

- Relevance: HIGH

- As Found: COVID-19

- ID: M10283

- Name: Infections

- Relevance: LOW

- As Found: Unknown

- ID: M6368

- Name: Communicable Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M17522

- Name: Virus Diseases

- Relevance: HIGH

- As Found: Virus Infection

- ID: M13904

- Name: Pneumonia

- Relevance: LOW

- As Found: Unknown

- ID: M13914

- Name: Pneumonia, Viral

- Relevance: LOW

- As Found: Unknown

- ID: M14978

- Name: Respiratory Tract Infections

- Relevance: LOW

- As Found: Unknown

- ID: M20490

- Name: Coronavirus Infections

- Relevance: LOW

- As Found: Unknown

- ID: M6555

- Name: Coronaviridae Infections

- Relevance: LOW

- As Found: Unknown

- ID: M23685

- Name: Nidovirales Infections

- Relevance: LOW

- As Found: Unknown

- ID: M15149

- Name: RNA Virus Infections

- Relevance: LOW

- As Found: Unknown

- ID: M11168

- Name: Lung Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14977

- Name: Respiratory Tract Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000086382

- Term: COVID-19

- ID: D000014777

- Term: Virus Diseases

### Intervention Browse Module - Browse Branches

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M17360

- Name: Vaccines

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-24
