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Standard vs High Prophylactic Doses or Anticoagulation in Patients With High Risk of Thrombosis Admitted With COVID-19 Pneumonia (PROTHROMCOVID)

Primary Purpose

Covid19, Thrombosis

Status
Completed
Phase
Not Applicable
Locations
Spain
Study Type
Interventional
Intervention
Tinzaparin
Sponsored by
Hospital Universitario Infanta Leonor
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Covid19

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Patients admitted to hospital with COVID-19, PCR and/or Antigens Test + SARS-CoV-2 infection or (presence of infiltrate compatible with Chest X-ray or TC)

  2. Patients with, at least, one of the following evolution disease risk criteria:

    • Sat 02<94%
    • Need for oxygen therapy or pAO2/FiO2<300mmHg or estimated PaO2/FiO2 based on SpO2/FiO2<300 mmHg.
    • DD>1000µg/L
    • PCR >150mg/L
    • IL6 >40pg/ml
  3. Age > 18 years
  4. Weight 50-100 Kg
  5. After receiving oral and written information about the study, patient must give Informed Consent duly signed and dated before performing any activity related to the study.

Exclusion Criteria:

  1. Patients who need mechanical ventilation (invasive or non-invasive), high flow nasal cannula or admission to ICU at the moment of randomization.
  2. Current diagnosis of acute bronchial asthma attack.
  3. History or clinical suspicion of pulmonary fibrosis.
  4. Current diagnosis or suspicion of pulmonary thromboembolism or deep vein thrombosis.
  5. Patients who need anticoagulant treatment due to previous venous or arterial thrombotic disease, or due to atrial fibrillation.
  6. Patients with pneumonectomy or lobectomy.
  7. Renal failure with Glomerular filtration <30 ml/min/1.73m2
  8. Patients with contraindication for anticoagulant treatment.
  9. Congenital bleeding disorders.
  10. Hypersensitivity to tinzaparin or UFH or some of its excipients.
  11. History of heparin-induced thrombocytopenia.
  12. Active bleeding or situation that predispose to bleeding.
  13. Moderate or severe anaemia (Hb<10 g/dl)
  14. Low platelet count < 80000/µl
  15. Patients with life expectancy less than 3 months due to primary disease evaluated by the physician.
  16. Patients currently intubated or intubated between the screening and the randomization.
  17. Pregnancy.

Sites / Locations

  • Complejo Hospitalario Universitario A Coruña
  • Hospital Universitario del Vinalopó
  • Hospital Clínic Barcelona
  • Hospital Universitario Vall d'Hebron
  • Hospital Universitario de Burgos
  • Hospital Virgen de la Luz
  • Hospital Universitari de Girona Doctor Josep Trueta
  • Hospital Clínico San Carlos
  • Hospital de Emergencias Enfermera Isabel Zendal
  • Hospital General Universitario Gregorio Marañón
  • Hospital Universitario 12 Octubre
  • Hospital Universitario Infanta Leonor
  • Hospital Universitario Infanta Sofía
  • Hospital Universitario Ramón y Cajal
  • Complexo Hospitalario Universitario de Pontevedra
  • Hospital Clínico Universitario de Valencia
  • Hospital Clínico Universitario de Valladolid
  • Hospital Álvaro Cunqueiro

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Active Comparator

Arm Label

Tinzaparin 4500 UI/day

Tinzaparin 100 UI/Kg/day

Tinzaparin 175 UI/Kg/day

Arm Description

Procedure: Tinzaparin 4500 UI/day SC until hospital discharge.

Procedure: Tinzaparin 100 UI/Kg/day SC until hospital discharge.

Procedure: Tinzaparin 175 UI/Kg/day SC until hospital discharge.

Outcomes

Primary Outcome Measures

Combined variable that includes outcomes 2, 3 and 4 detailed below
Combined variable that includes outcomes 2, 3 and 4 detailed below (reduction of suspicion of systemic thrombotic symptomatic events and/or need for mechanical ventilation and/or death at day 30 after randomization).
Reduction of suspicion of systemic thrombotic symptomatic events
Reduction of symptomatic thrombotic events: rate of venous thromboembolism confirmed by objective test.
Use of Mechanical ventilation invasive or non invasive including high flow nasal cannula oxigen
Mechanical ventilation (invasive or non-invasive) free survival.
Overall survival at 30 days.
Overall survival at 30 days: number of deaths.

Secondary Outcome Measures

Number of bleedings and adverse reactions
Safety of the different strategies of prophylaxis and anticoagulation: number of bleedings and adverse reactions in each group: Evaluation of the following variables: Incidence of major bleeding, defined as meeting any of these criteria: a) fatal bleeding or bleeding that occurs in a critical area or organ (for example, intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome), b ) causes a drop in hemoglobin level of 20 g/L or more, or c) requires the transfusion of 2 or more units of whole blood or packed red blood cells. Incidence of clinically relevant non-major bleeding: manifest, spontaneous or post-traumatic bleeding, which does not meet the criteria for major bleeding but which in the judgment of the investigator is relevant. Incidence of clinically relevant bleeding: all major and non-major hemorrhages clinically relevant. Incidence of adverse reactions.

Full Information

First Posted
January 14, 2021
Last Updated
September 13, 2022
Sponsor
Hospital Universitario Infanta Leonor
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1. Study Identification

Unique Protocol Identification Number
NCT04730856
Brief Title
Standard vs High Prophylactic Doses or Anticoagulation in Patients With High Risk of Thrombosis Admitted With COVID-19 Pneumonia (PROTHROMCOVID)
Official Title
Standard vs High Prophylactic Doses or Anticoagulation in Patients With High Risk of Thrombosis Admitted With COVID-19 Pneumonia (PROTHROMCOVID)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2022
Overall Recruitment Status
Completed
Study Start Date
February 1, 2021 (Actual)
Primary Completion Date
October 20, 2021 (Actual)
Study Completion Date
December 20, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospital Universitario Infanta Leonor

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The main objective is to evaluate the efficacy and safety of three doses of tinzaparin (prophylactic, intermediate and therapeutic) in hospitalized patients with COVID-19 pneumonia.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Covid19, Thrombosis

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
311 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Tinzaparin 4500 UI/day
Arm Type
Active Comparator
Arm Description
Procedure: Tinzaparin 4500 UI/day SC until hospital discharge.
Arm Title
Tinzaparin 100 UI/Kg/day
Arm Type
Active Comparator
Arm Description
Procedure: Tinzaparin 100 UI/Kg/day SC until hospital discharge.
Arm Title
Tinzaparin 175 UI/Kg/day
Arm Type
Active Comparator
Arm Description
Procedure: Tinzaparin 175 UI/Kg/day SC until hospital discharge.
Intervention Type
Drug
Intervention Name(s)
Tinzaparin
Intervention Description
day subcutaneously • Follow-up phase 1 (Day 15 to day 30): The information is obtained at discharge and on day +14, + 28 on 30 days. The latter information is obtained from patients, from medical records or by telephone contact at the patient's home. • Follow-up phase 2 (At 3 months: Information is obtained from patients, medical records, or by telephone contact at the patient's home.
Primary Outcome Measure Information:
Title
Combined variable that includes outcomes 2, 3 and 4 detailed below
Description
Combined variable that includes outcomes 2, 3 and 4 detailed below (reduction of suspicion of systemic thrombotic symptomatic events and/or need for mechanical ventilation and/or death at day 30 after randomization).
Time Frame
30 days
Title
Reduction of suspicion of systemic thrombotic symptomatic events
Description
Reduction of symptomatic thrombotic events: rate of venous thromboembolism confirmed by objective test.
Time Frame
30 days
Title
Use of Mechanical ventilation invasive or non invasive including high flow nasal cannula oxigen
Description
Mechanical ventilation (invasive or non-invasive) free survival.
Time Frame
30 days
Title
Overall survival at 30 days.
Description
Overall survival at 30 days: number of deaths.
Time Frame
30 days
Secondary Outcome Measure Information:
Title
Number of bleedings and adverse reactions
Description
Safety of the different strategies of prophylaxis and anticoagulation: number of bleedings and adverse reactions in each group: Evaluation of the following variables: Incidence of major bleeding, defined as meeting any of these criteria: a) fatal bleeding or bleeding that occurs in a critical area or organ (for example, intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome), b ) causes a drop in hemoglobin level of 20 g/L or more, or c) requires the transfusion of 2 or more units of whole blood or packed red blood cells. Incidence of clinically relevant non-major bleeding: manifest, spontaneous or post-traumatic bleeding, which does not meet the criteria for major bleeding but which in the judgment of the investigator is relevant. Incidence of clinically relevant bleeding: all major and non-major hemorrhages clinically relevant. Incidence of adverse reactions.
Time Frame
90 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients admitted to hospital with COVID-19, PCR and/or Antigens Test + SARS-CoV-2 infection or (presence of infiltrate compatible with Chest X-ray or TC) Patients with, at least, one of the following evolution disease risk criteria: Sat 02<94% Need for oxygen therapy or pAO2/FiO2<300mmHg or estimated PaO2/FiO2 based on SpO2/FiO2<300 mmHg. DD>1000µg/L PCR >150mg/L IL6 >40pg/ml Age > 18 years Weight 50-100 Kg After receiving oral and written information about the study, patient must give Informed Consent duly signed and dated before performing any activity related to the study. Exclusion Criteria: Patients who need mechanical ventilation (invasive or non-invasive), high flow nasal cannula or admission to ICU at the moment of randomization. Current diagnosis of acute bronchial asthma attack. History or clinical suspicion of pulmonary fibrosis. Current diagnosis or suspicion of pulmonary thromboembolism or deep vein thrombosis. Patients who need anticoagulant treatment due to previous venous or arterial thrombotic disease, or due to atrial fibrillation. Patients with pneumonectomy or lobectomy. Renal failure with Glomerular filtration <30 ml/min/1.73m2 Patients with contraindication for anticoagulant treatment. Congenital bleeding disorders. Hypersensitivity to tinzaparin or UFH or some of its excipients. History of heparin-induced thrombocytopenia. Active bleeding or situation that predispose to bleeding. Moderate or severe anaemia (Hb<10 g/dl) Low platelet count < 80000/µl Patients with life expectancy less than 3 months due to primary disease evaluated by the physician. Patients currently intubated or intubated between the screening and the randomization. Pregnancy.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nuria Muñoz Rivas
Organizational Affiliation
Hospital Universitario Infanta Leonor
Official's Role
Study Chair
Facility Information:
Facility Name
Complejo Hospitalario Universitario A Coruña
City
A Coruña
Country
Spain
Facility Name
Hospital Universitario del Vinalopó
City
Alicante
Country
Spain
Facility Name
Hospital Clínic Barcelona
City
Barcelona
Country
Spain
Facility Name
Hospital Universitario Vall d'Hebron
City
Barcelona
Country
Spain
Facility Name
Hospital Universitario de Burgos
City
Burgos
Country
Spain
Facility Name
Hospital Virgen de la Luz
City
Cuenca
Country
Spain
Facility Name
Hospital Universitari de Girona Doctor Josep Trueta
City
Girona
Country
Spain
Facility Name
Hospital Clínico San Carlos
City
Madrid
Country
Spain
Facility Name
Hospital de Emergencias Enfermera Isabel Zendal
City
Madrid
Country
Spain
Facility Name
Hospital General Universitario Gregorio Marañón
City
Madrid
Country
Spain
Facility Name
Hospital Universitario 12 Octubre
City
Madrid
Country
Spain
Facility Name
Hospital Universitario Infanta Leonor
City
Madrid
Country
Spain
Facility Name
Hospital Universitario Infanta Sofía
City
Madrid
Country
Spain
Facility Name
Hospital Universitario Ramón y Cajal
City
Madrid
Country
Spain
Facility Name
Complexo Hospitalario Universitario de Pontevedra
City
Pontevedra
Country
Spain
Facility Name
Hospital Clínico Universitario de Valencia
City
Valencia
Country
Spain
Facility Name
Hospital Clínico Universitario de Valladolid
City
Valladolid
Country
Spain
Facility Name
Hospital Álvaro Cunqueiro
City
Vigo
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
12865379
Citation
Lew TW, Kwek TK, Tai D, Earnest A, Loo S, Singh K, Kwan KM, Chan Y, Yim CF, Bek SL, Kor AC, Yap WS, Chelliah YR, Lai YC, Goh SK. Acute respiratory distress syndrome in critically ill patients with severe acute respiratory syndrome. JAMA. 2003 Jul 16;290(3):374-80. doi: 10.1001/jama.290.3.374.
Results Reference
background
PubMed Identifier
32311448
Citation
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.
Results Reference
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PubMed Identifier
32171076
Citation
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. Erratum In: Lancet. 2020 Mar 28;395(10229):1038. Lancet. 2020 Mar 28;395(10229):1038.
Results Reference
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PubMed Identifier
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Citation
Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24. Erratum In: Lancet. 2020 Jan 30;:
Results Reference
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PubMed Identifier
36233500
Citation
Munoz-Rivas N, Aibar J, Gabara-Xanco C, Trueba-Vicente A, Urbelz-Perez A, Gomez-Del Olmo V, Demelo-Rodriguez P, Rivera-Gallego A, Bosch-Nicolau P, Perez-Pinar M, Rios-Prego M, Madridano-Cobo O, Ramos-Alonso L, Alonso-Carrillo J, Francisco-Albelsa I, Marti-Saez E, Maestre-Peiro A, Mendez-Bailon M, Hernandez-Rivas JA, Torres-Macho J; PROTHROMCOVID Trial Investigators. Efficacy and Safety of Tinzaparin in Prophylactic, Intermediate and Therapeutic Doses in Non-Critically Ill Patients Hospitalized with COVID-19: The PROTHROMCOVID Randomized Controlled Trial. J Clin Med. 2022 Sep 24;11(19):5632. doi: 10.3390/jcm11195632.
Results Reference
derived

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Standard vs High Prophylactic Doses or Anticoagulation in Patients With High Risk of Thrombosis Admitted With COVID-19 Pneumonia (PROTHROMCOVID)

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