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

End-stage Heart Failure Clinical Trial

— IMPULSMACS  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04951999
• Other study ID #: APHP190830
• Secondary ID: 2020-A01450-39
• Status: Recruiting
• Phase: N/A
• Start date: December 2, 2021
• Est. completion date: October 17, 2024

Study information

• Verified date: November 2023
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Guillaume LEBRETON, MD, PhD
• Phone: +33142162979
• Email: guillaume.lebreton[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 70
• Est. completion date: October 17, 2024
• Est. primary completion date: May 2, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• End-stage Heart Failure
• Heart Failure

Intervention

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.

Locations

Country	Name	City	State
France	Groupement Hospitalier pitié Salpêtrière	Paris

Sponsors (4)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	ICAN Nutrition Education and Research, Institut National de la Santé Et de la Recherche Médicale, France, University Hospital, Lille

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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 period; After 7 days post-implantation : any transfusion of packed red blood cells.	6 months
Secondary	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 score; Hyperlactatemia >3 mmol/l; Hepatic cytolysis: increase in AST and/or ALT by a factor of 3 or more after implantation; Degradation 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
Secondary	Platelet dysfunction	Platelet dysfunction defined by a significant increase in circulating levels of p-selectin and glycocalicin between pre- and post-implantation	6 months
Secondary	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
Secondary	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
Secondary	Prolonged systemic inflammatory reaction syndrome	Monthly measures of following circulating inflammatory factors : TNFa et ß, NF kappab, TGF a /ß1/ß2,IFN? et ß, IL-1ß, 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-1ß(CCL4), MIP-3-beta (CCL19), 6Ckine(CCL21), MCD (CCL22) Myostatin, calveolin-1.	6 months
Secondary	Evolution of immune responses	Monthly phenotyping of monocytes and T cells	6 months
Secondary	Aortic valve fusion	Monthly echographic evaluation	6 months
Secondary	Aortic valve insufficiency	Monthly echographic evaluation	6 months
Secondary	Evaluation of cardiac recovery	Monthly exercise stress test evaluation (starting 2 months post-operative)	6 months