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

Sponsor

Hospital Universitario Infanta Leonor (Other)

Overall Status

Completed

CT.gov ID

NCT04730856

Collaborator

(none)

311

Enrollment

Locations

Arms

10.6

Actual Duration (Months)

17.3

Patients Per Site

1.6

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Covid19 Thrombosis	Drug: Tinzaparin	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

311 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

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

Actual Study Start Date :

Feb 1, 2021

Actual Primary Completion Date :

Oct 20, 2021

Actual Study Completion Date :

Dec 20, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Tinzaparin 4500 UI/day Procedure: Tinzaparin 4500 UI/day SC until hospital discharge.	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.
Active Comparator: Tinzaparin 100 UI/Kg/day Procedure: Tinzaparin 100 UI/Kg/day SC until hospital discharge.	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.
Active Comparator: Tinzaparin 175 UI/Kg/day Procedure: Tinzaparin 175 UI/Kg/day SC until hospital discharge.	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.

Arm

Intervention/Treatment

Active Comparator: Tinzaparin 4500 UI/day

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

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.

Active Comparator: Tinzaparin 100 UI/Kg/day

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

Drug: Tinzaparin

Active Comparator: Tinzaparin 175 UI/Kg/day

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

Drug: Tinzaparin

Outcome Measures

Primary Outcome Measures

Reduction of suspicion of systemic thrombotic symptomatic events [30 days]
Reduction of symptomatic thrombotic events: rate of venous thromboembolism confirmed by objective test.
Use of Mechanical ventilation [30 days]
Mechanical ventilation (invasive or non-invasive) free survival.
Progression on the WHO Progression Scale during follow-up. [30 days]
Progression on the WHO (World Health Organization) Progression Scale during follow-up. Score: 0 to 8 points. Worst situation corresponds to 8 points.
Overall survival at 30 days. [30 days]
Overall survival at 30 days: number of deaths.
Length of hospital stay (days) [30 days]
Length of hospital stay (days): number of days from hospital admission to hospital discharge
Length of ICU stay (days) [30 days]
Length of ICU stay (days): number of days from admission to ICU to discharge ICU

Secondary Outcome Measures

Number of bleedings and adverse reactions [90 days]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	Country
1	Complejo Hospitalario Universitario A Coruña	A Coruña	Spain
2	Hospital Universitario del Vinalopó	Alicante	Spain
3	Hospital Clínic Barcelona	Barcelona	Spain
4	Hospital Universitario Vall d'Hebron	Barcelona	Spain
5	Hospital Universitario de Burgos	Burgos	Spain
6	Hospital Virgen de la Luz	Cuenca	Spain
7	Hospital Universitari de Girona Doctor Josep Trueta	Girona	Spain
8	Hospital Clínico San Carlos	Madrid	Spain
9	Hospital de Emergencias Enfermera Isabel Zendal	Madrid	Spain
10	Hospital General Universitario Gregorio Marañón	Madrid	Spain
11	Hospital Universitario 12 Octubre	Madrid	Spain
12	Hospital Universitario Infanta Leonor	Madrid	Spain
13	Hospital Universitario Infanta Sofía	Madrid	Spain
14	Hospital Universitario Ramón y Cajal	Madrid	Spain
15	Complexo Hospitalario Universitario de Pontevedra	Pontevedra	Spain
16	Hospital Clínico Universitario de Valencia	Valencia	Spain
17	Hospital Clínico Universitario de Valladolid	Valladolid	Spain
18	Hospital Álvaro Cunqueiro	Vigo	Spain