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

Covid19 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04730856
• Other study ID #: PROTHROMCOVID
• Status: Completed
• Phase: N/A
• Start date: February 1, 2021
• Est. completion date: December 20, 2021

Study information

• Verified date: September 2022
• Source: Hospital Universitario Infanta Leonor
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 311
• Est. completion date: December 20, 2021
• Est. primary completion date: October 20, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• COVID-19
• Covid19
• Pneumonia
• Thrombosis

Intervention

Drug:
• Tinzaparin
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.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Universitario Infanta Leonor

Country where clinical trial is conducted

Spain, 

References & Publications (4)

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, Quéré 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. Review. — View 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 20 — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	30 days
Primary	Reduction of suspicion of systemic thrombotic symptomatic events	Reduction of symptomatic thrombotic events: rate of venous thromboembolism confirmed by objective test.	30 days
Primary	Use of Mechanical ventilation invasive or non invasive including high flow nasal cannula oxigen	Mechanical ventilation (invasive or non-invasive) free survival.	30 days
Primary	Overall survival at 30 days.	Overall survival at 30 days: number of deaths.	30 days
Secondary	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.	90 days