Clinical trial NCT04445935: Anticoagulation in Patients Suffering From COVID-19 Disease The ANTI-CO Trial
Official title: Anticoagulation in Patients Suffering From COVID-19 Disease-The Anti-Co Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Anticoagulation in COVID-19 ARDS
Keywords: COVID-19
ARDS
Anticoagulation
Lead sponsor: Hamad Medical Corporation
Sponsor class: INDUSTRY
First posted: 2020-06-24
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a randomized controlled trial.
Primary purpose: SUPPORTIVE_CARE

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.

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

Primary outcomes:
measure: P/F ratio
timeFrame: three days of intervention
Secondary outcomes:
measure: Kidney function
timeFrame: three days of intervention
Other outcomes:
Locations:
city: Doha
country: Qatar
facility: Hamad Medical Corporation
Study officials:
affiliation: HMC
name: Marcus Lance, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.