Anticoagulation in Patients Suffering From COVID-19 Disease The ANTI-CO Trial

NCT ID: NCT04445935

Last Updated: 2020-06-24

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-28
• Study Completion Date: 2021-03-28

Brief Summary

Patients with COVID-19 associated ARDS and mechanical ventilation have a high mortality. Part of the disease is an activation of the coagulation system which seems to contribute to clotformation in the pulmonary bloodstream. Recently we implemented an algorithm applying higher doses of heparins (LMWH). However, this approach could not inhibit clotformation enough. Bivalirudin could prevent clotformation better and support dissolving existing clots.

Therefore, we want to compare 50 patients with the standard treatment with 50 patients under bivalirudin treatment which we normally apply in patients with a HIT-syndrome.

Our primary outcome measure is oxygenation reflected as P/F ratio.

Detailed Description

The pandemic of COVID-19, a newly upcoming viral disease caused by SARS-CoV-2, puts the whole worlds health system under pressure.

Patients suffering from this disease mainly develop respiratory symptoms, which can lead to severe acute respiratory distress syndrome (ARDS) necessitating ICU admission in 10-20% of the cases admitted to hospital. In addition to these symptoms, patients show lymphopenia, cardiac symptoms and altered coagulation profiles. Although those patients are treated in the ICU the mortality there is more than 20% due to multiorgan failure.

One of the recent insights in this disease is its effect on the coagulation system. Meanwhile we know that the coagulation system gets activated. Furthermore, it seems that clot formation takes place in the pulmonary micro-vasculature which could contribute to the widely observed gas-exchange impairment. Therefore, many centers apply empiric anticoagulation for their COVID-patients. At the moment, we at HMC, also apply an empirical anticoagulation protocol as our standard approach. However, this is a symptomatic treatment without good proof.

Bivalirudin is a well-known agent which is used in HMC for cases in which anticoagulation is needed, but a contraindication for heparin exists (i.e. HIT syndrome). This drug has an interesting pharmacologic profile. It acts independent of antithrombin (AT), the physiological compound which enhances heparin effects under normal circumstances. This lack of dependence on AT, makes Bivalirudin an attractive choice in light of the contradictory reports on the levels of AT during COVID infection. If AT levels are decreased during the infection, heparin (as well as LMWH) cannot work efficiently, which would render our treatment less effective. Luckily, bivalirudin acts without the support of AT, so we could bypass this problem. In addition, bivalirudin has some fibrinolytic activities. It inhibits clot-bound thrombin which as a result destabilizes the clot rendering it more susceptible to thrombolysis. This property partially supports the dissolving of clots and could support re-opening the pulmonary microcirculation.

Objectives:

To prove the positive effect of anticoagulation with bivalirudin intravenously on gas-exchange in patients with COVID-19 and respiratory failure on invasive mechanical ventilation.

Conditions

Anticoagulation in COVID-19 ARDS

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: TRIPLE

Study Groups

Standard treatment

In this arm the patients will be treated according to our standard anticoagulation protocol.

The patients will not be treated with Bivalirudin (the investigational drug).

Group Type: ACTIVE_COMPARATOR

Standard treatment

Intervention Type: DRUG

This group will receive standard anticoagulation with LMWH/UFH

Bivalirudin arm

The patients will be anticoagulated according to the institutional HIT-protocol which uses Bivalirudin as anticoagulant.

Group Type: EXPERIMENTAL

Bivalirudin Injection

Intervention Type: DRUG

The patients will receive iv Bivalirudin according to the institutional HIT protocol.

Interventions

Bivalirudin Injection

The patients will receive iv Bivalirudin according to the institutional HIT protocol.

Intervention Type: DRUG

Standard treatment

This group will receive standard anticoagulation with LMWH/UFH

Intervention Type: DRUG

Other Intervention Names

anticoagulation

Eligibility Criteria

Inclusion Criteria

• Adult patient (≥ 18 years of age)
• Positive COVID-test
• Under mechanical ventilation
• D-Dimers>1.2 mg/L

Exclusion Criteria

• Pregnancy
• Allergy to the drug (bivalirudin)
• Inherited coagulation abnormalities
• No informed consent

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hamad Medical Corporation

INDUSTRY

Sponsor Role: lead

Responsible Party

Dr. Marcus Daniel Lance

Professor Dr. Marcus Lance

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Marcus Lance, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

HMC

Locations

Hamad Medical Corporation

Doha, , Qatar

Site Status: RECRUITING

Countries

Qatar

Central Contacts

Marcus Lance, MD, PhD

Role: CONTACT

mlance@hamad.qa

00974 ext. 33530292

Stefan Roehrig, MD, MBA

Role: CONTACT

srohrig@hamad.qa

00974 ext. 66030924

Facility Contacts

Nadir Kharma, MD

Role: primary

nkharma@hamad.qa

00974 ext. 55118621

References

Flumignan RL, Civile VT, Tinoco JDS, Pascoal PI, Areias LL, Matar CF, Tendal B, Trevisani VF, Atallah AN, Nakano LC. Anticoagulants for people hospitalised with COVID-19. Cochrane Database Syst Rev. 2022 Mar 4;3(3):CD013739. doi: 10.1002/14651858.CD013739.pub2.

Reference Type: DERIVED

PMID: 35244208 (View on PubMed)

Kharma N, Roehrig S, Shible AA, Elshafei MS, Osman D, Elsaid IM, Mustafa SF, Aldabi A, Smain OAM, Lance MD. Anticoagulation in critically ill patients on mechanical ventilation suffering from COVID-19 disease, The ANTI-CO trial: A structured summary of a study protocol for a randomised controlled trial. Trials. 2020 Sep 7;21(1):769. doi: 10.1186/s13063-020-04689-1.

Reference Type: DERIVED

PMID: 32895056 (View on PubMed)

Other Identifiers

MRC-05-082

Identifier Type: -

Identifier Source: org_study_id