Evaluation of Serial Ultrasound Screening in ICU COVID-19 Patients

Covid19 Clinical Trial

Official title:

Systematic Ultrasound Screening for Lower Extremity Deep Vein Thrombosis in ICU Patients With Severe COVID-19: a Randomized Clinical Trial.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05028244
• Other study ID #: P/R(AG)176/2021
• Status: Completed
• Phase: N/A
• Start date: April 1, 2021
• Est. completion date: December 13, 2021

Study information

• Verified date: April 2024
• Source: Hospital Universitari Vall d'Hebron Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This clinical trial is designed to evaluate if the periodic screening for deep venous thrombosis by ultrasound of lower extremity in patients with intensive care unit (ICU) patients with COVID 19 impacts on mortality, ICU stay and total length of stay in the hospital, along with other outcomes.

Description:

Background: COVID-19 has a high incidence of venous thromboembolic disease (VTE), especially pulmonary thromboembolism (PE) and deep vein thrombosis (DVT), with an even higher incidence in patients admitted to the intensive care unit (ICU). The presentation of these events is related to an increase in mortality and the mean stay in the ICU. The impact of systematic screening for asymptomatic lower extremity DVT in these patients has not been studied, so we propose to carry out a clinical trial to assess its impact in these patients.

Hypothesis: Serial DVT screening in patients admitted to the ICU for COVID-19 does not improve survival, mean stay, or the incidence of symptomatic VTE.

Objective: To study whether DVT screening in these patients has an impact on the incidence of symptomatic VTE, mortality and average stay in the ICU.

Methods: Non-blind randomized clinical trial on all patients aged 18 years or older admitted to the ICU for COVID-19 with less than 72 hours elapsed since their admission to the unit. Patients with DVT or PE will be excluded at the time of recruitment (all patients will be ruled out by routine ultrasound and computed tomography angiography (CT Angiography)); Pregnant patients, patients with a previous diagnosis of DVT or PE, and patients undergoing extracorporeal membrane oxygenation (ECMO) will also be excluded. Patients will be randomized into two arms at the time of inclusion: the screened group (Group 1) and the non-screened group (Group 2). Group 1: patients who will be treated according to the usual ICU protocol and, additionally, will undergo serial ultrasounds of the lower extremities twice a week (Monday and Thursday). Group 2: they will be treated according to the usual ICU protocol and no screening examinations will be performed. Patients will be followed until discharge from the ICU or death and up to a maximum of 3 weeks. The incidence of symptomatic VTE will be assessed, as well as all-cause mortality and days of stay in the ICU. Clinical and laboratory variables will be collected from each patient for subsequent statistical analysis.

Relevance: The thrombotic complications of COVID-19 are well described, as well as their high incidence in critically ill patients. This work aims to clarify the current doubts about the need for systematic DVT screening in these patients. If our hypothesis is verified, a limited resource such as ultrasound of the lower limbs could be saved, as well as the use of the necessary protection materials and, most importantly, avoid unnecessary exposure of health personnel with the consequent risk that it represents for other professionals and patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 168
• Est. completion date: December 13, 2021
• Est. primary completion date: August 15, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• COVID 19 patients in their first 72 hours of entering ICU

Exclusion Criteria:

• Pregnant patients

• Not COVID 19 confirmed patients by RCP

• Patients that are in Extracorporeal membrane oxygenation

• Patients with previous thrombotic disease

Related Conditions & MeSH terms

• Acute Lung Injury
• Bronchitis
• Communicable Diseases
• COVID-19
• COVID-19 Pneumonia
• Covid19
• Deep Vein Thrombosis
• Embolism
• Infections
• Pulmonary Embolism
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Newborn
• Respiratory Tract Infections
• Thrombosis
• Venous Thrombosis

Intervention

Diagnostic Test:
• venous ultrasound of lower extremity
Patients are explored for deep vein thrombosis in femoral-popliteal and distal veins of the legs with ultrasound compression and doppler flow evaluation

Locations

Country	Name	City	State
Spain	Hospital Universitari Vall d'Hebron	Barcelona

Sponsors (2)

Lead Sponsor	Collaborator
Hospital Universitari Vall d'Hebron Research Institute	Universitat Autonoma de Barcelona

Country where clinical trial is conducted

Spain, 

References & Publications (24)

Bellmunt-Montoya S, Riera C, Gil D, Rodriguez M, Garcia-Reyes M, Martinez-Carnovale L, Marrero C, Gil M, Ruiz-Rodriguez JC, Ferrer R, de Nadal M, Monreal M, Llagostera S. COVID-19 Infection in Critically Ill Patients Carries a High Risk of Venous Thrombo-embolism. Eur J Vasc Endovasc Surg. 2021 Apr;61(4):628-634. doi: 10.1016/j.ejvs.2020.12.015. Epub 2020 Dec 23. — View Citation

Bohula EA, Berg DD, Lopes MS, Connors JM, Babar I, Barnett CF, Chaudhry SP, Chopra A, Ginete W, Ieong MH, Katz JN, Kim EY, Kuder JF, Mazza E, McLean D, Mosier JM, Moskowitz A, Murphy SA, O'Donoghue ML, Park JG, Prasad R, Ruff CT, Shahrour MN, Sinha SS, Wiviott SD, Van Diepen S, Zainea M, Baird-Zars V, Sabatine MS, Morrow DA; COVID-PACT Investigators. Anticoagulation and Antiplatelet Therapy for Prevention of Venous and Arterial Thrombotic Events in Critically Ill Patients With COVID-19: COVID-PACT. Circulation. 2022 Nov;146(18):1344-1356. doi: 10.1161/CIRCULATIONAHA.122.061533. Epub 2022 Aug 29. — View Citation

Boonyawat K, Chantrathammachart P, Numthavaj P, Nanthatanti N, Phusanti S, Phuphuakrat A, Niparuck P, Angchaisuksiri P. Incidence of thromboembolism in patients with COVID-19: a systematic review and meta-analysis. Thromb J. 2020 Nov 23;18(1):34. doi: 10.1186/s12959-020-00248-5. Erratum In: Thromb J. 2020 Dec 29;18(1):39. — View Citation

Cui S, Chen S, Li X, Liu S, Wang F. Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia. J Thromb Haemost. 2020 Jun;18(6):1421-1424. doi: 10.1111/jth.14830. Epub 2020 May 6. — View Citation

Flumignan RL, Civile VT, Tinoco JDS, Pascoal PI, Areias LL, Matar CF, Tendal B, Trevisani VF, Atallah AN, Nakano LC. Anticoagulants for people hospitalised with COVID-19. Cochrane Database Syst Rev. 2022 Mar 4;3(3):CD013739. doi: 10.1002/14651858.CD013739.pub2. — View Citation

Gil-Sala D, Riera C, Garcia-Reyes M, Rodriguez M, Marrero CE, Martinez L, Gil M, Ruiz-Rodriguez JC, Ferrer R, DE Nadal M, Suito-Alcantara MA, Llagostera S, Bellmunt-Montoya S. Mortality and bleeding complications of COVID-19 critically ill patients with venous thromboembolism. Int Angiol. 2022 Feb;41(1):1-8. doi: 10.23736/S0392-9590.21.04704-0. Epub 2021 Nov 9. — View Citation

Jenner WJ, Kanji R, Mirsadraee S, Gue YX, Price S, Prasad S, Gorog DA. Thrombotic complications in 2928 patients with COVID-19 treated in intensive care: a systematic review. J Thromb Thrombolysis. 2021 Apr;51(3):595-607. doi: 10.1007/s11239-021-02394-7. Epub 2021 Feb 14. — View Citation

Jimenez D, Garcia-Sanchez A, Rali P, Muriel A, Bikdeli B, Ruiz-Artacho P, Le Mao R, Rodriguez C, Hunt BJ, Monreal M. Incidence of VTE and Bleeding Among Hospitalized Patients With Coronavirus Disease 2019: A Systematic Review and Meta-analysis. Chest. 2021 Mar;159(3):1182-1196. doi: 10.1016/j.chest.2020.11.005. Epub 2020 Nov 17. — View Citation

Klok FA, Kruip MJHA, van der Meer NJM, Arbous MS, Gommers D, Kant KM, Kaptein FHJ, van Paassen J, Stals MAM, Huisman MV, Endeman H. Confirmation of the high cumulative incidence of thrombotic complications in critically ill ICU patients with COVID-19: An updated analysis. Thromb Res. 2020 Jul;191:148-150. doi: 10.1016/j.thromres.2020.04.041. Epub 2020 Apr 30. — View Citation

Kollias A, Kyriakoulis KG, Lagou S, Kontopantelis E, Stergiou GS, Syrigos K. Venous thromboembolism in COVID-19: A systematic review and meta-analysis. Vasc Med. 2021 Aug;26(4):415-425. doi: 10.1177/1358863X21995566. Epub 2021 Apr 4. — View Citation

Malas MB, Naazie IN, Elsayed N, Mathlouthi A, Marmor R, Clary B. Thromboembolism risk of COVID-19 is high and associated with a higher risk of mortality: A systematic review and meta-analysis. EClinicalMedicine. 2020 Dec;29:100639. doi: 10.1016/j.eclinm.2020.100639. Epub 2020 Nov 20. — View Citation

Mansory EM, Srigunapalan S, Lazo-Langner A. Venous Thromboembolism in Hospitalized Critical and Noncritical COVID-19 Patients: A Systematic Review and Meta-analysis. TH Open. 2021 Jul 6;5(3):e286-e294. doi: 10.1055/s-0041-1730967. eCollection 2021 Jul. — View Citation

Mazzaccaro D, Giannetta M, Fancoli F, Milani V, Modafferi A, Malacrida G, Righini P, Marrocco-Trischitta MM, Nano G. COVID and venous thrombosis: systematic review of literature. J Cardiovasc Surg (Torino). 2021 Dec;62(6):548-557. doi: 10.23736/S0021-9509.21.12022-1. Epub 2021 Sep 14. — View Citation

Mohamed MFH, Al-Shokri SD, Shunnar KM, Mohamed SF, Najim MS, Ibrahim SI, Elewa H, Abdalla LO, El-Bardissy A, Elshafei MN, Abubeker IY, Danjuma M, Dousa KM, Yassin MA. Prevalence of Venous Thromboembolism in Critically Ill COVID-19 Patients: Systematic Review and Meta-Analysis. Front Cardiovasc Med. 2021 Jan 8;7:598846. doi: 10.3389/fcvm.2020.598846. eCollection 2020. — View Citation

Moonla C, Sosothikul D, Chiasakul T, Rojnuckarin P, Uaprasert N. Anticoagulation and In-Hospital Mortality From Coronavirus Disease 2019: A Systematic Review and Meta-Analysis. Clin Appl Thromb Hemost. 2021 Jan-Dec;27:10760296211008999. doi: 10.1177/10760296211008999. — View Citation

Reis S, Popp M, Schmid B, Stegemann M, Metzendorf MI, Kranke P, Meybohm P, Weibel S. Safety and Efficacy of Intermediate- and Therapeutic-Dose Anticoagulation for Hospitalised Patients with COVID-19: A Systematic Review and Meta-Analysis. J Clin Med. 2021 Dec 23;11(1):57. doi: 10.3390/jcm11010057. — View Citation

Sebuhyan M, Mirailles R, Crichi B, Frere C, Bonnin P, Bergeron-Lafaurie A, Denis B, Liegeon G, Peyrony O, Farge D; Saint-Louis CORE (COVID-19 RESEARCH) group. How to screen and diagnose deep venous thrombosis (DVT) in patients hospitalized for or suspected of COVID-19 infection, outside the intensive care units. J Med Vasc. 2020 Dec;45(6):334-343. doi: 10.1016/j.jdmv.2020.08.002. Epub 2020 Sep 4. — View Citation

Suh YJ, Hong H, Ohana M, Bompard F, Revel MP, Valle C, Gervaise A, Poissy J, Susen S, Hekimian G, Artifoni M, Periard D, Contou D, Delaloye J, Sanchez B, Fang C, Garzillo G, Robbie H, Yoon SH. Pulmonary Embolism and Deep Vein Thrombosis in COVID-19: A Systematic Review and Meta-Analysis. Radiology. 2021 Feb;298(2):E70-E80. doi: 10.1148/radiol.2020203557. Epub 2020 Dec 15. — View Citation

Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020 Apr;18(4):844-847. doi: 10.1111/jth.14768. Epub 2020 Mar 13. — View Citation

Tufano A, Rendina D, Abate V, Casoria A, Marra A, Buonanno P, Galletti F, Di Minno G, Servillo G, Vargas M. Venous Thromboembolism in COVID-19 Compared to Non-COVID-19 Cohorts: A Systematic Review with Meta-Analysis. J Clin Med. 2021 Oct 25;10(21):4925. doi: 10.3390/jcm10214925. — View Citation

Wells PS, Anderson DR, Bormanis J, Guy F, Mitchell M, Gray L, Clement C, Robinson KS, Lewandowski B. Value of assessment of pretest probability of deep-vein thrombosis in clinical management. Lancet. 1997 Dec 20-27;350(9094):1795-8. doi: 10.1016/S0140-6736(97)08140-3. — View Citation

Wu C, Liu Y, Cai X, Zhang W, Li Y, Fu C. Prevalence of Venous Thromboembolism in Critically Ill Patients With Coronavirus Disease 2019: A Meta-Analysis. Front Med (Lausanne). 2021 Apr 29;8:603558. doi: 10.3389/fmed.2021.603558. eCollection 2021. — View Citation

Xiao D, Tang F, Chen L, Gao H, Li X. Cumulative Evidence for the Association of Thrombosis and the Prognosis of COVID-19: Systematic Review and Meta-Analysis. Front Cardiovasc Med. 2022 Jan 25;8:819318. doi: 10.3389/fcvm.2021.819318. eCollection 2021. — View Citation

Zhang R, Ni L, Di X, Wang X, Ma B, Niu S, Liu C. Systematic review and meta-analysis of the prevalence of venous thromboembolic events in novel coronavirus disease-2019 patients. J Vasc Surg Venous Lymphat Disord. 2021 Mar;9(2):289-298.e5. doi: 10.1016/j.jvsv.2020.11.023. Epub 2020 Dec 9. — View Citation

* Note: There are 24 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mortality	Patients that die in ICU during follow up	21 days
Primary	ICU Stay	Number of days staying in that unit during follow up	21 days
Primary	Symptomatic deep venous thrombosis	presence of confirmed deep vein thrombosis and presence of symptoms	21 days
Secondary	composite outcome	a composite outcome with poor outcome factors (symptomatic DVT, bleeding, ICU stay >21 days)	21 days