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

Anticoagulation in COVID-19 ARDS Clinical Trial

Official title:

Anticoagulation in Patients Suffering From COVID-19 Disease-The Anti-Co Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04445935
• Other study ID #: MRC-05-082
• Status: Recruiting
• Phase: Phase 4
• Start date: June 28, 2020
• Est. completion date: March 28, 2021

Study information

• Verified date: June 2020
• Source: Hamad Medical Corporation
• Contact: Marcus Lance, MD, PhD
• Phone: 00974
• Email: mlance[@]hamad.qa
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: March 28, 2021
• Est. primary completion date: September 28, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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

Related Conditions & MeSH terms

• Anticoagulation in COVID-19 ARDS
• Stress, Psychological

Intervention

Drug:
• Bivalirudin Injection
The patients will receive iv Bivalirudin according to the institutional HIT protocol.
• Standard treatment
This group will receive standard anticoagulation with LMWH/UFH

Locations

Country	Name	City	State
Qatar	Hamad Medical Corporation	Doha

Sponsors (1)

Lead Sponsor	Collaborator
Hamad Medical Corporation

Country where clinical trial is conducted

Qatar, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	P/F ratio	the P/F ratio is a surrogate parameter for oxygenation in ARDS.	three days of intervention
Secondary	Kidney function	The kidney function frequently is deteriorated in COVID-19 patients	three days of intervention