Heparin-free Extracorporeal Membrane Oxygenation Support During Clinical Lung Transplantation (zero-hep)

An Investigation of Clinical Outcomes and Inflammatory Response to Heparin Free Extracorporeal Membrane Oxygenation Support During Clinical Lung Transplantation - a Prospective Double-blind Randomised Feasibility Study

The aim of this investigation is to compare two different anti-coagulation strategies in clinical lung transplantation where lung implantations are all routinely done on veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) support at the investigators' institution. No heparinization (Zero-Hep) will be compared to standard low-dose heparinization (Standard). Traditionally, the Vienna group has used a standard low-dose heparin protocol with unfractionated heparin (UFH) administered as a bolus upon ECMO cannulation. With heparin-coated tubing and intraoperative ECMO flow never falling below 1 L/min, the likelihood of thromboembolic events is believed to be negligible. To date, the investigators have not experienced any thromboembolic events during intra-operative ECMO use. On the other hand, the use of UFH entails an increased risk for bleeding, so it follows that avoidance of additional heparin may be beneficial. Generally, risks and benefits of heparinization during these short procedures have not yet been thoroughly analyzed. This study will investigate the feasibility of running heparin free VA-ECMO support during clinical lung transplantation and its effect on clinical outcomes and inflammatory response comparing 40 patients receiving a standard dose of heparin versus 40 patients receiving placebo in a randomized, double-blind study design.

Study Overview

• Status: Recruiting
• Conditions: Lung Transplantation
• Intervention / Treatment: Drug: Placebo; Drug: Heparin sodium

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Stefan Schwarz, MD PhD; Phone Number: 56440 +43 1 40400; Email: stefan.a.schwarz@meduniwien.ac.at

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Recruiting
    • Medical University of Vienna - Dept. of Thoracic Surgery
    • Contact: Stefan Schwarz, MD PhD; Phone Number: 56440 +43 1 40400; Email: stefan.a.schwarz@meduniwien.ac.at

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Double lung transplantation
• Age of 18 or older at the time of the procedure

Exclusion Criteria:

• Single lung transplantation
• Re-transplantation
• Previous major thoracic surgery (excluding pleural drainage, video-assisted thoracoscopic - (VATS) biopsy)
• ECMO bridge to transplantation
• Coronavirus(COVID) - acute respiratory distress syndrome (ARDS) as transplant indication
• Pre-operative anti-coagulation/anti-platelet treatment
• Paediatric transplantation
• Multi-organ transplantation
• Active pregnancy or breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Saline 0.9%	Drug: Placebo; Lung transplantation on central veno-arterial ECMO without additional heparin
Active Comparator: Heparin sodium; 70 international units (IU)/kg Heparin sodium	Drug: Heparin sodium; Lung transplantation on central veno-arterial ECMO with standard additional heparin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Arterial thromboembolic events	Including myocardial infarction, mesenteric infarction, hepatic infarction, spleen infarction, limb ischemia, cerebral stroke including transient ischemic attack	From time of intraoperative ECMO initiation, assessed uo to 3 weeks post-transplant
Venous thromboembolic events	deep vein thrombosis, pulmonary embolism, cerebral venous or cavernous sinus thrombosis	From time of intraoperative ECMO initiation, assessed up to 3 weeks post-transplant
Circuit-related thrombosis	requiring ECMO oxygenator exchange	From time of intraoperative ECMO initiation assessed until intraoperative ECMO decannulation

Collaborators and Investigators

• Sponsor: Medical University of Vienna
• Investigators: Principal Investigator: Konrad Hoetzenecker, MD PhD, Medical University of Vienna - Dept. of Thoracic Surgery

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2022
• Primary Completion (Anticipated): February 28, 2024
• Study Completion (Anticipated): June 30, 2024

Study Registration Dates

• First Submitted: January 12, 2023
• First Submitted That Met QC Criteria: January 21, 2023
• First Posted (Estimate): January 26, 2023

Study Record Updates

• Last Update Posted (Estimate): January 26, 2023
• Last Update Submitted That Met QC Criteria: January 21, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Heparin; Calcium heparin
• Other Study ID Numbers: 2128/2021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No