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Covid19Phase 4ACTIV-4ANCT04505774

Accelerating COVID-19 Therapeutic Interventions and Vaccines 4 ACUTE

A Phase 4 study testing theraputic heparin, prophylactic heparin and P2Y12 in people with Covid19, run by Matthew Neal MD at 101 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This is a randomized, open label, adaptive platform trial to compare the effectiveness of antithrombotic and additional strategies for prevention of adverse outcomes in COVID-19 positive inpatients Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Covid19
What is being tested?
theraputic heparin, prophylactic heparin and P2Y12
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3,591 participants
Where
101 sitesin 4 countries
Study dates
4 Sep 2020to 26 Jan 2024
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • ≥ 18 years of age
  • Hospitalized for COVID-19
  • Enrolled within 72 hours of hospital admittance or 72 hours of positive COVID test
  • Expected to require hospitalization for > 72 hours
  • Inclusion criteria contained in the master protocol in addition to the following:
  • Moderate illness severity - defined as non-ICU level of care at the time of randomization (not receiving high flow nasal oxygen (HFNO), non-invasive ventilation (NIV), invasive ventilation (IV), vasopressors or inotropes, or extracorporeal membrane oxygenation (ECMO) OR Severe illness severity - defined as ICU level of care at the time of randomization (receiving HFNO, NIV, IV, vasopressors or inotropes, or ECMO)
Show all 32Show fewer
  • For moderate illness severity, participants are required to meet one or more of the following risk criteria:
  • Age ≥ 65 years or
  • ≥2 of the following -
  • O2 supplementation > 2 liters per minute
  • BMI ≥ 35
  • GFR ≤ 60
  • History of Type 2 diabetes
  • History of heart failure (regardless of ejection fraction)
  • D dimer ≥ 2x the site's upper limit of normal (ULN)
  • Troponin ≥ 2x the site's ULN
  • BNP≥100 pg/mL or NT-proBNP≥300 pg/mL
  • CRP ≥50 mg/L
  • Inclusion criteria contained in the master protocol in addition to the following:
  • Moderate illness severity - defined as non-ICU level of care at the time of randomization (not receiving high flow nasal oxygen (HFNO), non-invasive ventilation (NIV), invasive ventilation (IV), vasopressors or inotropes, or extracorporeal membrane oxygenation (ECMO)) OR Severe illness severity - defined as ICU level of care at the time of randomization (receiving HFNO, NIV, IV, vasopressors or inotropes, or ECMO)
  • For moderate illness severity, participants are required to meet one or more of the following risk criteria:
  • Age ≥ 65 years or
  • ≥2 of the following-
  • O2 supplementation > 2 liters per minute
  • BMI ≥ 35
  • GFR ≤ 60
  • History of Type 2 diabetes
  • History of heart failure (regardless of ejection fraction)
  • D dimer ≥ 2x the site's upper limit of normal (ULN)
  • Troponin ≥ 2x the site's ULN
  • BNP≥100 pg/mL or NT-proBNP≥300 pg/mL
  • CRP ≥50 mg/L

Who cannot join

  • Imminent death
  • Requirement for chronic mechanical ventilation via tracheostomy prior to hospitalization
  • Pregnancy
  • Any condition that, in the opinion of the investigator, precludes the use of crizanlizumab such as uncontrolled bleeding or severe anemia (hemoglobin<4 g/dL)
  • Open label treatment with crizanlizumab within the past three months
  • In addition to the exclusion criteria noted in the master protocol, arm-specific exclusion criteria are as follows:
Show all 13Show fewer
  • Known hypersensitivity to any SGLT2 inhibitors
  • Type 1 diabetes
  • History of diabetic ketoacidosis
  • eGFR <20 and/or requirement for renal replacement therapy
  • Open label treatment with any SGLT2 inhibitor
  • Based on a recommendation from the ACTIV4 DSMB on December 19, 2020, enrollment of patients requiring ICU level of care into the therapeutic anti-coagulation arm was stopped due to meeting a futility threshold and a potential for harm for this sub-group could not be excluded. Enrollment continues for moderately ill hospitalized COVID-19 patients.
  • Based on a recommendation from the ACTIV4 DSMB on June 18, 2021, enrollment of patients not requiring ICU level of care and randomized to P2Y12 or standard care was stopped due to meeting a futility threshold. Enrollment continues for severely ill (ICU level of care) hospitalized COVID-19 patients.

Trial locations and contacts

101 sites in 4 countries.

101 sites in 4 countries

United States81 sites

  • Cleveland Clinic Akron General

    Akron, Ohio, 44307

  • Albany Medical College

    Albany, New York, 12208

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • Emory

    Atlanta, Georgia, 30308

  • Morehouse School of Medicine

    Atlanta, Georgia, 30310

  • University of Texas at Austin

    Austin, Texas, 78701

  • Memorial Hospital

    Belleville, Illinois, 62226

  • University of Alabama

    Birmingham, Alabama, 35233

  • Boston University

    Boston, Massachusetts, 02118

  • St Elizabeth's Medical Center

    Brighton, Massachusetts, 02135

  • Mercy Hospital Buffalo

    Buffalo, New York, 14220

  • Cooper Health

    Camden, New Jersey, 08103

  • Cook County Health

    Chicago, Illinois, 60612

  • University of Illinois at Chicago Health (UIH)

    Chicago, Illinois, 60612

  • University of Cincinnati Medical Center

    Cincinnati, Ohio, 45219

  • The MetroHealth System

    Cleveland, Ohio, 44109

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Ohio State Universtiy Wexner Medical Center

    Columbus, Ohio, 43210

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75390

  • Geisinger Research

    Danville, Pennsylvania, 17822

  • Denver Health and Hospital Authority

    Denver, Colorado, 80401

  • Wayne State University

    Detroit, Michigan, 48201

  • Doylestown Cardiology Associates

    Doylestown, Pennsylvania, 18901

  • Duke University Hospital

    Durham, North Carolina, 27704

  • Englewood Health

    Englewood, New Jersey, 07631

  • OSF Little Company of Mary Medical Center (OSF LCM)

    Evergreen Park, Illinois, 60805

  • Kaiser Permanente Fontana

    Fontana, California, 92335

  • Medical City Ft Worth

    Fort Worth, Texas, 76104

  • University of Florida

    Gainesville, Florida, 32608

  • St. Mary's Hospital & Regional Medical Center

    Grand Junction, Colorado, 81501

  • Saint Francis Hospital and Medical Center

    Hartford, Connecticut, 06105

  • Penn State Health Milton S. Hershey Medical Center

    Hershey, Pennsylvania, 17033

  • Queens Medical Center

    Honolulu, Hawaii, 96813

  • Indiana University Health Methodist Hospital

    Indianapolis, Iowa, 46202

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • Memorial Hospital

    Jacksonville, Florida, 32216

  • Kansas University Medical Center

    Kansas City, Kansas, 66160

  • University Medical Center of Southern Nevada

    Las Vegas, Nevada, 89102

  • University of Arkansas for Medical Sciences

    Little Rock, Arkansas, 72205

  • Kaiser Permanente Los Angeles

    Los Angeles, California, 90027

  • Smidt Heart Institute at Cedars-Sinai

    Los Angeles, California, 90048

  • Ronald Reagan UCLA Medical Center

    Los Angeles, California, 90095

  • University of Wisconsin Hospital; Meriter Hospital (UW affiliated)

    Madison, Wisconsin, 53715

  • Hennepin County Medical Center

    Minneapolis, Minnesota, 55415

  • West Virginia University CTR

    Morgantown, West Virginia, 26506

  • Atlantic Health System

    Morristown, New Jersey, 07960

  • Sarah Cannon and HCA Research Institute

    Nashville, Tennessee, 37203

  • Skyline Medical Center

    Nashville, Tennessee, 37207

  • Ochsner Clinic Foundation

    New Orleans, Louisiana, 70121

  • VA New York Harbor Healthcare System

    New York, New York, 10010

  • NYU Langone

    New York, New York, 10016

  • Mt. Sinai Hospital

    New York, New York, 10029

  • Rutgers New Jersey Medical School

    Newark, New Jersey, 07103

  • Hospital of the University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Temple University

    Philadelphia, Pennsylvania, 19141

  • UPMC Presbyterian

    Pittsburgh, Pennsylvania, 15260

  • AtlantiCare Regional Medical Center

    Pomona, New Jersey, 08240

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • Rhode Island Hospital

    Providence, Rhode Island, 02903

  • The Miriam Hospital

    Providence, Rhode Island, 02906

  • HCA Henrico Doctors Hospital

    Richmond, Virginia, 23229

  • UC San Diego Hillcrest

    San Diego, California, 92103

  • Zuckerberg San Francisco General Hospital

    San Francisco, California, 94110

  • UCSF San Francisco

    San Francisco, California, 94143

  • Zuckerberg San Francisco General Hospital

    San Francisco, California, 94410

  • Swedish Hospital

    Seattle, Washington, 98122

  • Baystate Medical Center

    Springfield, Massachusetts, 01199

  • Washington University School of Medicine, ACCS Research

    St Louis, Missouri, 63110

  • Stanford University Medical Center

    Stanford, California, 94305

  • SUNY Upstate University Hospital

    Syracuse, New York, 13210

  • AdventHealth Tampa

    Tampa, Florida, 33613

  • Baylor Scott and White Medical Center - Temple

    Temple, Texas, 76508

  • Jacobi Medical Center

    The Bronx, New York, 10461

  • Montefiore Medical Center

    The Bronx, New York, 10461

  • Mercy Health St Vincent Medical Center

    Toledo, Ohio, 43608

  • Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

    Torrance, California, 90502

  • University of Arizona

    Tucson, Arizona, 85719

  • Ascension St. John Clinical Research Institute

    Tulsa, Oklahoma, 74104

  • Westchester Medical Center

    Valhalla, New York, 10595

  • Wake Forest

    Winston-Salem, North Carolina, 27157

  • University of Massachusetts

    Worcester, Massachusetts, 01655

Other trials in United States

Italy7 sites

  • Azienda Ospedaliero Sant Anna e San Sebastiano

    Caserta

  • Maria Cecilia Hospital , Cotignola, Ravenna

    Cotignola

  • Università degli Studi di Ferrara, Ferrara

    Ferrara

  • Azienda Ospedaliero -Universitaria Careggi

    Florence

  • Policlinico di Napoli, Napoli

    Naples

  • AOU Policlinico di Palermo, Palermo

    Palermo

  • ASL-1 Imperiese, Sanremo

    Sanremo

Other trials in Italy

Spain7 sites

  • Hospital Universitario A Coruna

    A Coruña

  • Hospital Virgen del Mar

    Almería

  • Hospital Arnau de Vilanova

    Lleida

  • Hospital Universitario La Paz

    Madrid

  • Hospital Universitario Ramon Y Cajal

    Madrid

  • Hospital Clínico Universitario de Salamanca

    Salamanca

  • Hospital Clínico Universitario de Santiago de Compostela

    Santiago de Compostela

Other trials in Spain

Brazil6 sites

  • Hospital Universitario Sao Francisco de Assis

    Bragança Paulista

  • União Brasileira de Educação e Assistência - Hospital São Lucas da PUCRS

    Porto Alegre

  • Centro de Estudos Clínicos do Hospital Cárdio Pulmonar

    Salvador

  • Fundação Faculdade Regional De Medicina De São José Do Rio Preto

    São José do Rio Preto

  • Instituto Dante Pazzanese de Cardiologia

    São Paulo

  • Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da USP-InCor-HCFMUSP

    São Paulo

Other trials in Brazil

About this study

Official title: A Multicenter, Adaptive, Randomized Controlled Platform Trial of the Safety and Efficacy of Antithrombotic and Additional Strategies in Hospitalized Adults With COVID-19

This is a randomized, open label, adaptive platform trial to compare the effectiveness of antithrombotic and additional strategies for prevention of adverse outcomes in COVID-19 positive inpatients

Read the detailed description

The severe acute respiratory syndrome coronavirus 2, which causes the highly contagious coronavirus disease 2019 (COVID-19), has resulted in a global pandemic.

The clinical spectrum of COVID-19 infection is broad, encompassing asymptomatic infection, mild upper respiratory tract illness, and severe viral pneumonia with respiratory failure and death. The risk of thrombotic complications is increased, even as compared to other viral respiratory illnesses, such as influenza. A pro-inflammatory cytokine response as well as induction of procoagulant factors associated with COVID-19 has been proposed to contribute to thrombosis as well as plaque rupture through local inflammation. Patients with COVID-19 are at increased risk for arterial and vein thromboembolism, with high rates observed despite thromboprophylaxis. Autopsy reports have noted micro and macro vascular thrombosis across multiple organ beds consistent with an early hypercoagulable state.

Notably, in COVID-19, data in the U.K. and U.S. document that infection and outcomes of infection are worse in African and Hispanic descent persons than in other groups. The reasons for this are uncertain.

Viral Infection and Thrombosis A large body of literature links inflammation and coagulation; altered hemostasis is a known complication of respiratory viral infections. Procoagulant markers are severely elevated in viral infections. Specifically, proinflammatory cytokines in viral infections upregulate expression of tissue factor, markers of thrombin generation, platelet activation, and down-regulate natural anticoagulant proteins C and S.

Studies have demonstrated significant risk of deep venous thrombosis (DVT), pulmonary embolism (PE), and myocardial infarction (MI) associated with viral respiratory infections. In a series of patients with fatal influenza H1N1, 75% had pulmonary thrombi on autopsy (a rate considerably higher than reported on autopsy studies among the general intensive care unit population). Incidence ratio for acute myocardial infarction in the context of Influenza A is over 10. Severe acute respiratory syndrome coronavirus-1 (SARS CoV-1) and influenza have been associated with disseminated intravascular coagulation (DIC), endothelial damage, DVT, PE, and large artery ischemic stroke. Patients with Influenza H1N1 and acute respiratory distress syndrome (ARDS) had a 23.3-fold higher risk for pulmonary embolism, and a 17.9-fold increased risk for deep vein thrombosis. Compared to those treated with systemic anticoagulation, those without treatment were 33 times more likely to suffer a VTE.

Thrombosis, both microvascular and macrovascular, is a prominent feature in multiple organs at autopsy in fatal cases of COVID-19. Thrombosis may thus contribute to respiratory failure, renal failure, and hepatic injury in COVID-19. The number of megakaryocytes in tissues is higher than in other forms of ARDS, and thrombi are platelet-rich based on specific staining. Thrombotic stroke has been reported in young COVID-19 patients with no cardiovascular risk factors. Both arterial and venous thrombotic events have been seen in increasing numbers of hospitalized patients infected with COVID-19. The incidence of thrombosis has ranged from 10 to 30% in hospitalized patients; however, this varies by type of thrombosis captured (arterial or vein) and severity of illness (ICU level care, requiring mechanical ventilation, etc.).

Additional treatment strategies Data from the multiplatform randomized controlled trial (mpRCT) demonstrated that (1) therapeutic dose anticoagulation with heparin was not beneficial in improving clinical outcomes compared to standard of care prophylactic dose heparin in severely ill (ICU level of care) patients, and (2) therapeutic dose anticoagulation with heparin was beneficial in improving organ support free days compared to standard of care prophylactic dose heparin in moderately ill (hospitalized and not requiring organ support) patients. However, there remains significant residual risk for adverse clinical outcomes and excess mortality for severely ill as well as moderately ill patients.

Antithrombotic regimens that are shown to be efficacious will be combined in clinical practice with other agents to treat COVID-19 hospitalized patients. This adaptive platform trial will test other promising agents when added to proven therapies, such as heparin. The rationale and risks for each agent will be included in the arm-specific appendix. Two specific agents to be added as arms, effective October 2021, include the P-selectin inhibitor, Crizanlizumab as well as SGLT2 inhibitors. P-selectin may play a proximal role in the inflammatory and thrombotic cascade in patients with COVID-19 and P-selectin inhibition may be a effective in preventing downstream sequelae. In addition, SGLT-2 inhibitors have been shown to decrease capillary leak and may promote vascular integrity in COVID-19.

This platform trial will have multiple arms, which may be dropped or added as the platform trial progresses. Sample size will be flexible: the trial will be stopped for efficacy or futility based on pre-determined statistical thresholds as defined in the arm-specific appendices. Each arm will have an adaptive component for determinations of futility or success.

Randomization assignments are at the participant level, stratified by enrolling site and by ICU level of care vs non-ICU level of care and/or other arm-specific criteria.

Conditions
Covid19
Being tested
theraputic heparin, prophylactic heparin, P2Y12, Crizanlizumab Injection, SGLT2 inhibitor
Keywords
anti-coagulation, antithrombosis, anticoagulation, ACTIV, inpatient, heparin, p2y12, endothelial dysfunction, vascular integrity, P-selectin, crizanlizumab, SGLT-2 inhibitor
Medical subject headings
COVID-19

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • theraputic heparinDrug

    Also called unfractionated heparin, Enoxaparin, Dalteparin, Tinzaparin

    increased dose of heparin above standard of care.

  • prophylactic heparinDrug

    Also called enoxaparin, dalteparin, Tinzaparin, Fondparinux

    standard of care dose of heparin

  • P2Y12Drug

    Also called Ticagrelor, Prasugrel, Clopidogrel

    added P2Y12 inhibitor

  • Crizanlizumab InjectionDrug

    crizanlizumab injection

  • SGLT2 inhibitorDrug

    Also called dapagliflozin, empagliflozin, canagliflozin, ertugliflozin

    sglt2 inhibitor

Study groups in NCT04505774
Study groupRoleWhat they receive
Therapeutic Dose AnticoagulationOtherincreased dose of heparin above standard of care. 1.0 - This arm was stopped in severe patients in December 2020 and results are published in PMID: 34351722 (NEJM, August, 2021) (see reference section for citation). This arm was stopped for moderate patients in January 2021.
Receives: Drug: theraputic heparin
Prophylactic Dose AnticoagulationOtherHeparin standard of care 1.0 - this arm was stopped for all patients in January, 2021 and results are published in PMID: 34351721 (NEJM, August, 2021) (see reference section for citation)
Receives: Drug: prophylactic heparin
Therapeutic Dose Anticoagulation + P2Y12 inhibitorOtherincreased dose of heparin above standard of care with an added P2Y12 inhibitor This Arm enrolled moderate illness patients only. Enrollment of moderate illness patients in the trial was ended per DSMB on June 19, 2021 and results are published in PMID: PMID: 35040887 (JAMA, January, 2022) (see reference section for citation)
Receives: Drug: theraputic heparin; Drug: P2Y12
Prophylactic Dose Anticoagulation + P2Y12 inhibitorOtherHeparin standard of care with an added P2Y12 inhibitor This Arm enrolled severe illness patients only. Enrollment of severe illness patients in the trial was ended per DSMB in June 2022.
Receives: Drug: prophylactic heparin; Drug: P2Y12
Standard of Care + CrizanlizumabOtherStandard of care plus crizanlizumab infusion This arm will enroll moderate and severe illness patients This arm was ended for all patients per the DSMB in September 2022.
Receives: Drug: Crizanlizumab Injection
Standard of Care + SGLT2 inhibitorOtherStandard of care plus SGLT2 inhibitor This arm will enroll moderate and severe illness patients This arm was ended in March 2023
Receives: Drug: SGLT2 inhibitor
Standard of Care (SGLT2 arm)OtherStandard of care only This arm will enroll moderate and severe illness patients This arm was ended in March 2023
Receives: Drug: SGLT2 inhibitor
Standard of Care (Criza)OtherStandard of care only This arm will enroll moderate and severe illness patients This arm was ended for all patients per the DSMB in September 2022.
Receives: Drug: Crizanlizumab Injection

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 21 Day Organ Support (Respiratory or Vasopressor) Free Days

    which is defined as the number of days that a patient is alive and free of organ support through the first 21 days after trial entry. Organ Support is defined as receipt of non-invasive mechanical ventilation, high flow nasal canula oxygen, mechanical ventilation, or vasopressor therapy, with death at any time during the index hospitalization assigned -1 days.

    This outcome variable was designed to exceed day 21 on the IQR. It goes above 21 days because it include baseline day 0 in their design.

    Measured: 21 days from study enrollment

Secondary outcomes (10)

  1. Death Within 28 Days

    Measured: 28 days from enrollment

  2. Acute Kidney Injury

    Acute Kidney Injury Acute kidney injury after enrollment is defined by KDIGO criteria for Acute Kidney Injury in the setting of not meeting these criteria upon enrollment: Modified Stages: ∙ Stage 2: Serum Cr 2.0-2.9 times baseline ∙ Stage 3: Serum Cr ≥ 3.0 times baseline, OR Increase in serum creatinine to ≥ 4.0mg/dl, OR Initiation of renal replacement therapy

    Measured: 90 days from enrollment

  3. Major Thrombotic Event or in Hospital Death

    A composite endpoint of death, pulmonary embolism, systemic arterial thromboembolism, myocardial infarction, or ischemic stroke during hospitalization or at 28 days after enrollment (whichever is earlier) - "major thrombotic events or death"

    Measured: 28 days

  4. Any Thrombotic Event or in Hospital Death

    A composite endpoint of death, pulmonary embolism, systemic arterial thromboembolism, myocardial infarction, DVT, or ischemic stroke during hospitalization or at 28 days after enrollment (whichever is earlier)

    Measured: 28 days

  5. Any Renal Replacement Therapy

    Measured: 28 days

  6. Days Free of Organ Support and Renal Replacement Therapy

    This outcome variable was designed to exceed day 28 on the IQR. It goes above 28 days because it include baseline day 0 in their design.

    Measured: 28 days

  7. Ventilator Free Days up to Day 28

    This outcome variable was designed to exceed day 28 on the IQR. It goes above 28 days because it include baseline day 0 in their design.

    Measured: 28 days

  8. Days Free of Vasopressors

    This outcome variable was designed to exceed day 28 on the IQR. It goes above 28 days because it include baseline day 0 in their design.

    Measured: 28 days

  9. Progression to Intubation or Death

    analysis completed on the Heparin protocol

    Measured: 28 days

  10. Survival Until Discharge

    Measured: 28 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Aug 2020
  2. Study start4 Sep 2020
  3. Primary completion31 Aug 2023
  4. Study completion26 Jan 2024

Resources

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
Treatment
Allocation
Randomised
Intervention model
Sequential
Model description
This is an adaptive design
Masking
None (open label)
Enrolment
3,591 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04505774
Sponsor's protocol ID
ACTIV-4 ACUTE
Other IDs
1OT2HL156812-01
Acronym
ACTIV-4A
Status last verified
Dec 2024
First submitted
6 Aug 2020
Last updated
30 Dec 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Data will be shared as per NIH guidelines.

Publications

  • Bikdeli B, Madhavan MV, Jimenez D, Chuich T, Dreyfus I, Driggin E, Nigoghossian C, Ageno W, Madjid M, Guo Y, Tang LV, Hu Y, Giri J, Cushman M, Quere I, Dimakakos EP, Gibson CM, Lippi G, Favaloro EJ, Fareed J, Caprini JA, Tafur AJ, Burton JR, Francese DP, Wang EY, Falanga A, McLintock C, Hunt BJ, Spyropoulos AC, Barnes GD, Eikelboom JW, Weinberg I, Schulman S, Carrier M, Piazza G, Beckman JA, Steg PG, Stone GW, Rosenkranz S, Goldhaber SZ, Parikh SA, Monreal M, Krumholz HM, Konstantinides SV, Weitz JI, Lip GYH; Global COVID-19 Thrombosis Collaborative Group, Endorsed by the ISTH, NATF, ESVM, and the IUA, Supported by the ESC Working Group on Pulmonary Circulation and Right Ventricular Function. COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-Up: JACC State-of-the-Art Review. J Am Coll Cardiol. 2020 Jun 16;75(23):2950-2973. doi: 10.1016/j.jacc.2020.04.031. Epub 2020 Apr 17.

    PubMed 32311448

  • Klok FA, Kruip MJHA, van der Meer NJM, Arbous MS, Gommers DAMPJ, Kant KM, Kaptein FHJ, van Paassen J, Stals MAM, Huisman MV, Endeman H. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res. 2020 Jul;191:145-147. doi: 10.1016/j.thromres.2020.04.013. Epub 2020 Apr 10.

    PubMed 32291094

  • Middeldorp S, Coppens M, van Haaps TF, Foppen M, Vlaar AP, Muller MCA, Bouman CCS, Beenen LFM, Kootte RS, Heijmans J, Smits LP, Bonta PI, van Es N. Incidence of venous thromboembolism in hospitalized patients with COVID-19. J Thromb Haemost. 2020 Aug;18(8):1995-2002. doi: 10.1111/jth.14888. Epub 2020 Jul 27.

    PubMed 32369666

  • Poissy J, Goutay J, Caplan M, Parmentier E, Duburcq T, Lassalle F, Jeanpierre E, Rauch A, Labreuche J, Susen S; Lille ICU Haemostasis COVID-19 Group. Pulmonary Embolism in Patients With COVID-19: Awareness of an Increased Prevalence. Circulation. 2020 Jul 14;142(2):184-186. doi: 10.1161/CIRCULATIONAHA.120.047430. Epub 2020 Apr 24. No abstract available.

    PubMed 32330083

  • Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-1062. doi: 10.1016/S0140-6736(20)30566-3. Epub 2020 Mar 11.

    PubMed 32171076

  • Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost. 2020 May;18(5):1094-1099. doi: 10.1111/jth.14817. Epub 2020 Apr 27.

    PubMed 32220112

  • Wang L, Zhao L, Li F, Liu J, Zhang L, Li Q, Gu J, Liang S, Zhao Q, Liu J, Xu JF. Risk assessment of venous thromboembolism and bleeding in COVID-19 patients. Clin Respir J. 2022 Mar;16(3):182-189. doi: 10.1111/crj.13467. Epub 2022 Jan 21.

    PubMed 35060325

  • Danzi GB, Loffi M, Galeazzi G, Gherbesi E. Acute pulmonary embolism and COVID-19 pneumonia: a random association? Eur Heart J. 2020 May 14;41(19):1858. doi: 10.1093/eurheartj/ehaa254. No abstract available.

    PubMed 32227120

  • Xie Y, Wang X, Yang P, Zhang S. COVID-19 Complicated by Acute Pulmonary Embolism. Radiol Cardiothorac Imaging. 2020 Mar 16;2(2):e200067. doi: 10.1148/ryct.2020200067. eCollection 2020 Apr. No abstract available.

    PubMed 33778561

  • Beristain-Covarrubias N, Perez-Toledo M, Thomas MR, Henderson IR, Watson SP, Cunningham AF. Understanding Infection-Induced Thrombosis: Lessons Learned From Animal Models. Front Immunol. 2019 Nov 5;10:2569. doi: 10.3389/fimmu.2019.02569. eCollection 2019.

    PubMed 31749809

  • Clayton TC, Gaskin M, Meade TW. Recent respiratory infection and risk of venous thromboembolism: case-control study through a general practice database. Int J Epidemiol. 2011 Jun;40(3):819-27. doi: 10.1093/ije/dyr012. Epub 2011 Feb 15.

    PubMed 21324940

  • Goeijenbier M, van Wissen M, van de Weg C, Jong E, Gerdes VE, Meijers JC, Brandjes DP, van Gorp EC. Review: Viral infections and mechanisms of thrombosis and bleeding. J Med Virol. 2012 Oct;84(10):1680-96. doi: 10.1002/jmv.23354.

    PubMed 22930518

  • Smeeth L, Cook C, Thomas S, Hall AJ, Hubbard R, Vallance P. Risk of deep vein thrombosis and pulmonary embolism after acute infection in a community setting. Lancet. 2006 Apr 1;367(9516):1075-1079. doi: 10.1016/S0140-6736(06)68474-2.

    PubMed 16581406

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Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing theraputic heparin, prophylactic heparin and P2Y12 in people with Covid19, run by Matthew Neal MD at 101 sites in 4 countries.

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 32 inclusion and 13 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: finished, as of the sponsor's last update on 30 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 101 sites in United States, Italy, Spain, Brazil. 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?

Yes. Results are posted in the registry (first posted 30 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

21 Day Organ Support (Respiratory or Vasopressor) Free Days (time frame: 21 days from study enrollment). 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 NCT04505774, which also lists 40 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 30 Dec 2024.

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