AssocIation of PULSatility and Occurrence of Complications Related to Mechanically Assisted Circulatory Support (IMPULSMACS)

The primary objective of this study is to determine whether preserved pulsatility for patients supported by CF-LVAD (continuous flow Left Ventricular Assist Device) is associated with less acquired deficiency of the Von Willebrand factor, a blood glycoprotein involved in hemostasis.

Study Overview

• Status: Recruiting
• Conditions: End-stage Heart Failure
• Intervention / Treatment: Other: Blood sampling

Detailed Description

Implantation of LVADs (Left Ventricular Assist Device) is a medium to long-term therapeutic option for patients with end-stage heart failure and isolated left ventricular dysfunction. Nevertheless, LVADs use remain limited by the frequency of their adverse effects, most of which being unpredictable. In the literature, loss of pulsatility seems to be associated with CF-LVADs complications, including bleeding. Accordingly, the primary objective of this study is to determine whether patient's preserved pulsatility is associated with less acquired deficiency of the Von Willebrand factor (VWF), a blood glycoprotein involved in hemostasis. This deficiency, characterized by a decrease or absence of VWF High Molecular Weight Multimers (HMWMs), is present to varying degrees in almost all patients with LVADs and is a major risk factor for bleeding complications in these patients. Pulsatility is estimated by the patient's blood pressure differential, measured 1) at discharge from the operating room (=transfer to care), 2) at discharge from care (=transfer to his or her room), 3) at discharge from the hospital (=transfer to rehabilitation), and then at each follow-up visit up to 6 months post-implantation. The primary endpoint is to determine whether a preserved pulsatility is associated with less acquired deficiency of the Von Willebrand factor ratio of High Molecular Weight Multimers (HMWMs).

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Guillaume LEBRETON, MD, PhD; Phone Number: +33142162979; Email: guillaume.lebreton@aphp.fr
• Study Contact Backup: Name: Pascal LEPRINCE, MD, PhD; Phone Number: +33 1 42 16 56 32; Email: pascal.leprince@aphp.fr

Study Locations

• France
  • Paris, France, 75013
    • Recruiting
    • Groupement Hospitalier pitié Salpêtrière
    • Contact: Guillaume Lebreton, MD,PhD; Phone Number: 33142162979; Email: guillaume.lebreton@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients over 18 years of age
2. Patients for whom a decision to implant a left-sided monoventricular assist has been retained after discussion in the RCP of heart failure, transplantation and circulatory assistance (whatever the therapeutic strategy envisaged: waiting for transplantation, recovery or destination therapy).
3. Patients affiliated to a social security system (beneficiaries or beneficiaries entitled to benefits, excluding AME)
4. Signature of an informed consent by the patient or by the trusted person, or a close relative, if the patient is not able to do so

Exclusion Criteria:

1. Heart transplant patients
2. Patients who already had LVAD
3. Chronic renal failure patients on dialysis
4. Patients refusing to give informed consent
5. Patients deprived of liberty or under legal protection (guardianship, curators)
6. Pregnant or breastfeeding women
7. Ongoing participation in another intervention research protocol except LEVOECMO project (NCT04728932) and ANCHOR project (NCT04184635)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Blood sampling	Other: Blood sampling; For 10 visits (out of the 12 of the protocol), ~40 ml of blood is sampled for research purposes in addition to care sampling.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Von Willebrand factor high molecular weight multimers (HMWM) ratio	Comparison of Von Willebrand factor high molecular weight multimers (HMWM) ratio at LVAD pre-implantation and at day 30. Measure of an correlation between preserved pulsatility and the HMWM ratio evolution during the first month after implantation.	30 days after LVAD IMPLANTATION

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severe postoperative gastrointestinal bleeding	Track record of patients undergoing gastrointestinal bleeding, identified by a decreased hemoglobin level associated with chronic iron deficiency anemia of unexplained cause and melena or bleeding demonstrated by exploration of the gastrointestinal tract by esophageal endoscopy, colonoscopy, or endoscopic videoscopy and resulting in any of the following: Death; Re-operation; Hospitalization; An erythrocyte transfusion defined as:Within 7 days of implantation :; Patients weighing 50 kg or more: ≥ 4U of packed red blood cells in a 24-hour period.; Patients weighing less than 50 kg: ≥ 20 mL/kg of packed red blood cells over a 24-hour periodAfter 7 days post-implantation : any transfusion of packed red blood cells.	6 months
Post-operative right ventricular failure	Track record of patients undergoing right ventricular failure, identified by: Elevation of central venous pressure (CVP) >16 mmHg by direct or echocardiographic measurement (inferior vena cava diameter >20 mm and respiratory variations <50%) for more than 48 hours; and at least one of the following signs of hemodynamic failure persisting for more than 48 hours:Increased inotropic scoreHyperlactatemia >3 mmol/lHepatic cytolysis: increase in AST and/or ALT by a factor of 3 or more after implantationDegradation of renal function (AKIN grade 2: creatinine elevation > 50% compared with before explantation and diuresis < 0.5 ml/kg/24h for 12 hours)Implantation of right temporary circulatory support (ECMO)	6 months
Platelet dysfunction	Platelet dysfunction defined by a significant increase in circulating levels of p-selectin and glycocalicin between pre- and post-implantation	6 months
Post-operative transient or permanent ischemic attack	Track record of patients undergoing ischemic attack (between 24 hours and 6 months post-operative) as assessed per INTERMACS definition	6 months
Vascular endothelium dysfunction	Vascular endothelial dysfunction defined by a significant increase in circulating levels of syndecan, thrombomodulin, TFPI and PAI-1 between pre- and post-implantation	6 months
Prolonged systemic inflammatory reaction syndrome	Monthly measures of following circulating inflammatory factors : TNFα et β, NF kappab, TGF α /β1/β2,IFNγ et β, IL-1β, IL-1RA, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p40, IL12-P70, IL-17, IL17A et F,CX3CL1 (fractalkine),MCP-1(CCL2), MIP-1 (CCL3), MIP-1β(CCL4), MIP-3-beta (CCL19), 6Ckine(CCL21), MCD (CCL22) Myostatin, calveolin-1.	6 months
Evolution of immune responses	Monthly phenotyping of monocytes and T cells	6 months
Aortic valve fusion	Monthly echographic evaluation	6 months
Aortic valve insufficiency	Monthly echographic evaluation	6 months
Evaluation of cardiac recovery	Monthly exercise stress test evaluation (starting 2 months post-operative)	6 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Institut National de la Santé Et de la Recherche Médicale, France; University Hospital, Lille; ICAN Nutrition Education and Research
• Investigators: Principal Investigator: Guillaume LEBRETON, MD, PhD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): December 2, 2021
• Primary Completion (Estimated): May 2, 2024
• Study Completion (Estimated): October 17, 2024

Study Registration Dates

• First Submitted: June 14, 2021
• First Submitted That Met QC Criteria: June 26, 2021
• First Posted (Actual): July 7, 2021

Study Record Updates

• Last Update Posted (Actual): November 22, 2023
• Last Update Submitted That Met QC Criteria: November 20, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: LVAD; Von Willebrand Factor; pulsatility index
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: APHP190830; 2020-A01450-39 (Other Identifier: ANSM)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The procedures carried out with the French data privacy authority (CNIL, Commission nationale de l'informatique et des libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients. Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations.
• IPD Sharing Time Frame: Beginning 3 months and ending 3 years following article publication. Requests out of these time frame can also be submitted to the sponsor
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

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