Clinical trial NCT04730856: 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
Overall status: COMPLETED
Phase: NA
Conditions: Covid19
Thrombosis
Lead sponsor: Hospital Universitario Infanta Leonor
Sponsor class: OTHER
First posted: 2021-01-29
Enrollment: 311
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Combined variable that includes outcomes 2, 3 and 4 detailed below
timeFrame: 30 days
measure: Reduction of suspicion of systemic thrombotic symptomatic events
timeFrame: 30 days
measure: Use of Mechanical ventilation invasive or non invasive including high flow nasal cannula oxigen
timeFrame: 30 days
measure: Overall survival at 30 days.
timeFrame: 30 days
Secondary outcomes:
measure: Number of bleedings and adverse reactions
timeFrame: 90 days
Other outcomes:
Locations:
city: A Coruña
country: Spain
facility: Complejo Hospitalario Universitario A Coruña
city: Alicante
country: Spain
facility: Hospital Universitario del Vinalopó
city: Barcelona
country: Spain
facility: Hospital Clínic Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Burgos
country: Spain
facility: Hospital Universitario de Burgos
city: Cuenca
country: Spain
facility: Hospital Virgen de la Luz
city: Girona
country: Spain
facility: Hospital Universitari de Girona Doctor Josep Trueta
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital de Emergencias Enfermera Isabel Zendal
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Universitario 12 Octubre
city: Madrid
country: Spain
facility: Hospital Universitario Infanta Leonor
city: Madrid
country: Spain
facility: Hospital Universitario Infanta Sofía
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Pontevedra
country: Spain
facility: Complexo Hospitalario Universitario de Pontevedra
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Valladolid
country: Spain
facility: Hospital Clínico Universitario de Valladolid
city: Vigo
country: Spain
facility: Hospital Álvaro Cunqueiro
Study officials:
affiliation: Hospital Universitario Infanta Leonor
name: Nuria Muñoz Rivas
role: STUDY_CHAIR
References:
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.
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.
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.
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.
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.