Anticoagulation in COVID-19 ARDSPhase 4NCT04445935
Anticoagulation in Patients Suffering From COVID-19 Disease The ANTI-CO Trial
A Phase 4 study testing Bivalirudin Injection and Standard treatment in people with Anticoagulation in COVID-19 ARDS, run by Hamad Medical Corporation at 1 site in Qatar.
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). Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Anticoagulation in COVID-19 ARDS
- What is being tested?
- Bivalirudin Injection and Standard treatment
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteQatar
- Study dates
- 28 Jun 2020to 28 Mar 2021
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patient (≥ 18 years of age)
- Positive COVID-test
- Under mechanical ventilation
- D-Dimers>1.2 mg/L
Who cannot join
- Pregnancy
- Allergy to the drug (bivalirudin)
- Inherited coagulation abnormalities
- No informed consent
Trial locations and contacts
1 site in 1 country.
Qatar1 site, 1 recruiting
- Recruiting
Hamad Medical Corporation
Doha
Nadir Kharma, MD, 00974 ext. 55118621, nkharma@hamad.qa
About this study
Official title: Anticoagulation in Patients Suffering From COVID-19 Disease-The Anti-Co Trial
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.
Read the 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
- Being tested
- Bivalirudin Injection, Standard treatment
- Keywords
- COVID-19, ARDS, Anticoagulation
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bivalirudin InjectionDrug
Also called anticoagulation
The patients will receive iv Bivalirudin according to the institutional HIT protocol.
This group will receive standard anticoagulation with LMWH/UFH
| Study group | Role | What they receive |
|---|---|---|
| Standard treatment | Active comparator | 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). Receives: Drug: Standard treatment |
| Bivalirudin arm | Experimental | The patients will be anticoagulated according to the institutional HIT-protocol which uses Bivalirudin as anticoagulant. Receives: Drug: Bivalirudin Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
P/F ratio
the P/F ratio is a surrogate parameter for oxygenation in ARDS.
Measured: three days of intervention
Secondary outcomes (1)
Kidney function
The kidney function frequently is deteriorated in COVID-19 patients
Measured: three days of intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2020
- Study start28 Jun 2020 (estimated)
- Primary completion28 Sep 2020 (estimated)
- Study completion28 Mar 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Anticoagulation in COVID-19 ARDSStudies of the same condition, open and under way.
- More trials run by Hamad Medical CorporationThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a randomized controlled trial.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hamad Medical Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Principal investigator, Dr. Marcus Daniel Lance, Hamad Medical Corporation
- Investigators
- Marcus Lance, MD, PhD, Principal investigator, HMC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04445935
- Sponsor's protocol ID
- MRC-05-082
- Status last verified
- Jun 2020
- First submitted
- 23 Jun 2020
- Last updated
- 24 Jun 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: this will depend on IRB advice
Publications
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: a rapid review. Cochrane Database Syst Rev. 2022 Mar 4;3(3):CD013739. doi: 10.1002/14651858.CD013739.pub2.
PubMed 35244208Kharma 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.
PubMed 32895056
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Anticoagulation in Patients Suffering From COVID-19 Disease-The Anti-Co Trial
- ClinicalTrials.gov ID
- NCT04445935
- Acronym / sponsor ID
- MRC-05-082
- Conditions
- Anticoagulation in COVID-19 ARDS
- Keywords
- COVID-19, ARDS, Anticoagulation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Hamad Medical CorporationIndustry (pharma, biotech, devices)
- Study start
- 28 Jun 2020 (estimated)
- Primary completion
- 28 Sep 2020 (estimated)
- Study completion
- 28 Mar 2021 (estimated)
- First posted
- 24 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- This is a randomized controlled trial.
| Arm | Type | Receives |
|---|---|---|
| Standard treatment | Active comparator | Drug: Standard treatmentIn this arm the patients will be treated according to our standard anticoagulation protocol. The patients will not be treated with Bivalirudin (the investigational drug). |
| Bivalirudin arm | Experimental | Drug: Bivalirudin InjectionThe patients will be anticoagulated according to the institutional HIT-protocol which uses Bivalirudin as anticoagulant. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Adult patient (≥ 18 years of age)
- Positive COVID-test
- Under mechanical ventilation
- D-Dimers>1.2 mg/L
Key exclusion criteria (4 listed)
- Pregnancy
- Allergy to the drug (bivalirudin)
- Inherited coagulation abnormalities
- No informed consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bivalirudin InjectionAlso: anticoagulationThe patients will receive iv Bivalirudin according to the institutional HIT protocol. | Drug | Bivalirudin arm |
| Standard treatmentThis group will receive standard anticoagulation with LMWH/UFH | Drug | Standard treatment |
Primary outcome
P/F ratio
Time frame: three days of intervention
the P/F ratio is a surrogate parameter for oxygenation in ARDS.
1 secondary outcome
Kidney function
Time frame: three days of intervention
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2020.
- Derived from this study: PubMed 35244208Flumignan 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: a rapid review. Cochrane Database Syst Rev. 2022 Mar 4;3(3):CD013739. doi: 10.1002/14651858.CD013739.pub2.
- Derived from this study: PubMed 32895056Kharma 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.
- Individual participant dataSharing planned: Undecided. this will depend on IRB advice
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marcus Lance, MD, PhD principal investigator
HMC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Bivalirudin Injection and Standard treatment in people with Anticoagulation in COVID-19 ARDS, run by Hamad Medical Corporation at 1 site in Qatar.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 24 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Qatar. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Marcus Lance, MD, PhD (00974 ext. 33530292, mlance@hamad.qa), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
P/F ratio (time frame: three days of intervention). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04445935, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jun 2020.