40 Participants Needed

Anticoagulation-free ECMO for Respiratory Insufficiency

(A-FREE ECMO Trial)

EF
DR
Overseen ByDamian Ratano, MD
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety of using ECMO (a machine that aids breathing) without the usual blood-thinning medicine for individuals with severe breathing problems known as ARDS. Typically, blood thinners prevent clots, but some studies have suggested they might not be necessary. The trial will compare two groups: one receiving the standard blood-thinning treatment (such as subcutaneous heparin, an anticoagulant) and another using only a basic clot prevention method. Eligible participants are those using ECMO for ARDS who can tolerate blood thinners. As a Phase 2, Phase 3 trial, this research evaluates the treatment's effectiveness in an initial group and represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking advancements in ARDS treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but if you are on chronic anticoagulation therapy, you cannot participate. This suggests you may need to stop such medications to join the trial.

What prior data suggests that this anticoagulation-free strategy for VV-ECMO is safe?

Research has shown that unfractionated heparin, a type of blood thinner, is commonly used for patients on ECMO, a machine that aids breathing. One study found it can sometimes reduce bleeding risk. However, bleeding and clotting issues remain major concerns with ECMO.

Some studies suggest ECMO might be safe without blood thinners like heparin. They recommend standard methods to prevent blood clots, such as administering heparin under the skin. This less aggressive approach could be safer for some patients.

In this trial, one group will not receive the usual blood thinner, unfractionated heparin, while on ECMO. Instead, they will receive standard clot prevention treatment with under-the-skin heparin or enoxaparin, another blood thinner. Previous patients using these methods have generally tolerated them well.

Overall, promising evidence supports these approaches, but bleeding and clotting risks remain. This trial tests safety and feasibility, aiming to learn more about the effectiveness of these methods without full anticoagulation.12345

Why are researchers excited about this trial?

Researchers are excited about the anticoagulation-free ECMO approach because it potentially eliminates the need for anticoagulation therapy, which is standard during ECMO treatment. Typically, unfractionated heparin is used to prevent blood clots in patients undergoing ECMO, but it comes with a risk of bleeding. By exploring the use of ECMO without anticoagulation, while still providing standard venous thromboembolism prophylaxis with subcutaneous enoxaparin or heparin, this trial aims to reduce bleeding risks while maintaining patient safety. This could lead to safer ECMO protocols for patients with respiratory insufficiency.

What evidence suggests that this trial's treatments could be effective for respiratory insufficiency?

Research has shown that during veno-venous extracorporeal membrane oxygenation (VV-ECMO), subcutaneous heparin is commonly used to prevent blood clots, which pose a risk during the procedure. In this trial, one group of participants will receive the standard anticoagulation care with unfractionated heparin during ECMO. Another group will not receive unfractionated heparin during ECMO but will instead receive standard venous thromboembolism prophylaxis with subcutaneous enoxaparin or unfractionated heparin. Some reports suggest that using VV-ECMO without stronger blood-thinning medication might be safe, potentially reducing bleeding risks. Although no large, controlled studies have confirmed this yet, these reports provide early indications that a no-anticoagulation approach might be feasible. Further research is necessary to confirm its safety and effectiveness.12678

Who Is on the Research Team?

EF

Eddy Fan, MD, PhD

Principal Investigator

University Health Network, Toronto

DR

Damian Ratano, MD

Principal Investigator

University Health Network, Toronto

Are You a Good Fit for This Trial?

This trial is for adults with Acute Respiratory Distress Syndrome (ARDS) who are on VV-ECMO treatment. It's not open to those with a history of heparin-induced thrombocytopenia, active bleeding, recent surgeries that don't allow anticoagulation, or if they need anticoagulants for other conditions like blood clots.

Inclusion Criteria

I am an adult with ARDS and am on a VV-ECMO machine.

Exclusion Criteria

I cannot take heparin due to allergies, bleeding, or recent surgery.
You are receiving a low amount of blood flow support through a special machine called VV-ECMO.
I am on blood thinners for a clot in my lung or leg.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive VV-ECMO with or without anticoagulation for acute respiratory failure

2 weeks
Daily monitoring during ECMO

Follow-up

Participants are monitored for safety and effectiveness after ECMO treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

  • Subcutaneous Heparin

Trial Overview

The study is testing the safety and feasibility of using VV-ECMO without the standard blood-thinning medication (therapeutic anticoagulation). Participants will receive subcutaneous Heparin instead to see if it can prevent clotting complications safely.

How Is the Trial Designed?

2

Treatment groups

Experimental Treatment

Active Control

Group I: No anticoagulationExperimental Treatment1 Intervention
Group II: Anticoagulation, ECMO standard of careActive Control1 Intervention

Find a Clinic Near You

Who Is Running the Clinical Trial?

Damian Ratano

Lead Sponsor

Trials
2
Recruited
100+

PSI Foundation, Toronto, Ontario

Collaborator

Trials
1
Recruited
40+

The Physicians' Services Incorporated Foundation

Collaborator

Trials
165
Recruited
31,700+

Citations

Anticoagulation Management During ECMO: Narrative ...

Extracorporeal membrane oxygenation is a life-saving intervention for critically ill patients with severe respiratory or cardiac failure. It ...

Anticoagulation-free VV ECMO for Acute Respiratory Failure

Failure to submit primary and secondary outcomes. Correction: Shown when the FDA confirms that the responsible party has updated the study record to correct ...

Anticoagulation in adult patients supported with ...

... dysfunction of heparin-coated MOs ... Efficacy and safety of argatroban in patients with acute respiratory distress syndrome and extracorporeal lung support.

Is an extended dose of subcutaneous nadroparin ...

These criteria included adult patients with severe acute respiratory distress syndrome (ARDS), a PaO2/FiO2 ratio below 100, unresponsive to standard treatments ...

Subcutaneous Enoxaparin for Systemic Anticoagulation of ...

... respiratory distress syndrome during extracorporeal membrane oxygenation. Compared to unfractionated heparin, we found that enoxaparin was ...

Safety of low-dose anticoagulation in extracorporeal ...

Bleeding and thrombosis are major complications associated with high mortality in extracorporeal membrane oxygenation (ECMO) management.

Effect of Unfractionated Heparin Dose on Complement ...

We investigated the impact of UFH dose during ECMO therapy at the coagulation–inflammation interface level, focusing on complement activation and changes in ...

Anticoagulation in venovenous extracorporeal membrane ...

An altered heparin response is common in ECMO patients, with a prevalence of 17–50% (30, 31). In patients with COVID-19, heparin resistance is even more ...