Covid19NCT04730856
Standard vs High Prophylactic Doses or Anticoagulation in Patients With High Risk of Thrombosis Admitted With COVID-19 Pneumonia (PROTHROMCOVID)
A study testing Tinzaparin in people with Covid19 and Thrombosis, run by Hospital Universitario Infanta Leonor at 18 sites in Spain.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Covid19, Thrombosis
- What is being tested?
- Tinzaparin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 311 participants
- Where
- 18 sitesSpain
- Study dates
- 1 Feb 2021to 20 Dec 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
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
- 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
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
18 sites in 1 country.
18 sites in 1 country
Spain18 sites
Complejo Hospitalario Universitario A Coruña
A Coruña
Hospital Universitario del Vinalopó
Alicante
Hospital Clínic Barcelona
Barcelona
Hospital Universitario Vall d'Hebron
Barcelona
Hospital Universitario de Burgos
Burgos
Hospital Virgen de la Luz
Cuenca
Hospital Universitari de Girona Doctor Josep Trueta
Girona
Hospital Clínico San Carlos
Madrid
Hospital de Emergencias Enfermera Isabel Zendal
Madrid
Hospital General Universitario Gregorio Marañón
Madrid
Hospital Universitario 12 Octubre
Madrid
Hospital Universitario Infanta Leonor
Madrid
Hospital Universitario Infanta Sofía
Madrid
Hospital Universitario Ramón y Cajal
Madrid
Complexo Hospitalario Universitario de Pontevedra
Pontevedra
Hospital Clínico Universitario de Valencia
Valencia
Hospital Clínico Universitario de Valladolid
Valladolid
Hospital Álvaro Cunqueiro
Vigo
About this study
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.
- Conditions
- Covid19, Thrombosis
- Being tested
- Tinzaparin
- Medical subject headings
- COVID-19, Thrombosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TinzaparinDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Tinzaparin 4500 UI/day | Active comparator | Procedure: Tinzaparin 4500 UI/day SC until hospital discharge. Receives: Drug: Tinzaparin |
| Tinzaparin 100 UI/Kg/day | Active comparator | Procedure: Tinzaparin 100 UI/Kg/day SC until hospital discharge. Receives: Drug: Tinzaparin |
| Tinzaparin 175 UI/Kg/day | Active comparator | Procedure: Tinzaparin 175 UI/Kg/day SC until hospital discharge. Receives: Drug: Tinzaparin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 30 days
Reduction of suspicion of systemic thrombotic symptomatic events
Reduction of symptomatic thrombotic events: rate of venous thromboembolism confirmed by objective test.
Measured: 30 days
Use of Mechanical ventilation invasive or non invasive including high flow nasal cannula oxigen
Mechanical ventilation (invasive or non-invasive) free survival.
Measured: 30 days
Overall survival at 30 days.
Overall survival at 30 days: number of deaths.
Measured: 30 days
Secondary outcomes (1)
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:
- 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.
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2021
- Study start1 Feb 2021
- Primary completion20 Oct 2021
- Study completion20 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Covid19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 311 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital Universitario Infanta Leonor
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Nuria Muñoz Rivas, Study chair, Hospital Universitario Infanta Leonor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04730856
- Sponsor's protocol ID
- PROTHROMCOVID
- Status last verified
- Sep 2022
- First submitted
- 14 Jan 2021
- Last updated
- 15 Sep 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 12865379Bikdeli 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 32311448Zhou 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 32171076Huang 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.
PubMed 31986264Munoz-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.
PubMed 36233500
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Standard vs High Prophylactic Doses or Anticoagulation in Patients With High Risk of Thrombosis Admitted With COVID-19 Pneumonia (PROTHROMCOVID)
- ClinicalTrials.gov ID
- NCT04730856
- Acronym / sponsor ID
- PROTHROMCOVID
- Conditions
- Covid19, Thrombosis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 311 participants (actual)
- Lead sponsor
- Hospital Universitario Infanta LeonorUniversity, hospital or other
- Study start
- 1 Feb 2021 (actual)
- Primary completion
- 20 Oct 2021 (actual)
- Study completion
- 20 Dec 2021 (actual)
- First posted
- 29 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Tinzaparin 4500 UI/day | Active comparator | Drug: TinzaparinProcedure: Tinzaparin 4500 UI/day SC until hospital discharge. |
| Tinzaparin 100 UI/Kg/day | Active comparator | Drug: TinzaparinProcedure: Tinzaparin 100 UI/Kg/day SC until hospital discharge. |
| Tinzaparin 175 UI/Kg/day | Active comparator | Drug: TinzaparinProcedure: Tinzaparin 175 UI/Kg/day SC until hospital discharge. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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:
- 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.
Key exclusion criteria (17 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tinzaparinday 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. | Drug | Tinzaparin 100 UI/Kg/day, Tinzaparin 175 UI/Kg/day, Tinzaparin 4500 UI/day |
Primary outcome
Combined variable that includes outcomes 2, 3 and 4 detailed below
Time frame: 30 days
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
Time frame: 30 days
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
Time frame: 30 days
Mechanical ventilation (invasive or non-invasive) free survival.
Overall survival at 30 days.
Time frame: 30 days
Overall survival at 30 days: number of deaths.
1 secondary outcome
Number of bleedings and adverse reactions
Time frame: 90 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2022.
- Background: PubMed 12865379Lew 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.
- Background: PubMed 32311448Bikdeli 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.
- Background: PubMed 32171076Zhou 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.
- Results publication: PubMed 31986264Huang 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.
- Derived from this study: PubMed 36233500Munoz-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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nuria Muñoz Rivas study chair
Hospital Universitario Infanta Leonor
18 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Tinzaparin in people with Covid19 and Thrombosis, run by Hospital Universitario Infanta Leonor at 18 sites in Spain.
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 10 inclusion and 17 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 15 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in Spain. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Combined variable that includes outcomes 2, 3 and 4 detailed below (time frame: 30 days). The study lists 4 primary outcomes in all. 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 NCT04730856, which also lists 5 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 15 Sep 2022.