Safe Delivery of Thrombolytic Treatment for Pulmonary Embolism Using ClotPro® Viscoelastic Tests

NCT06667882 | Completed

• 1 other identifier: 65187-5/2021/EÜIG
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this work was to reduce the bleeding risk during thrombolysis using the viscoelastic blood coagulation tests.

Conditions

Pulmonary Embolism Subacute Massive; Complication of Treatment; Fibrinolysis; Hemorrhage

Outcome Measures

Primary Outcomes (3)

• Major, life threatening bleeding due to profuse bleeding

  Hemorrhagic shock due to profuse bleeding: * hemoglobin reduction \> 30 g/l AND * Systolic blood pressure \< 90 mmHg OR * Reduction in systolic blood pressure \> 40 mmHg OR * Preserved systolic blood pressure achieved through increased dose of inotropic/vasopressor therapy

  during the treatment with tPA (on the control arm 2 hours, on the intervention arm variable > 2 hours)

• Major, life threatening bleeding due to intracranial haemorrhage

  Intracranial hemorrhage - new onset of neurological symptoms

  during the treatment with tPA (on the control arm 2 hours, on the intervention arm variable > 2 hours)

• Minor bleeding: Haemoglobin reduction > 10g/l during the treatment

  Haemoglobin reduction \> 10g/l, but less, than 30 g/l

  during the treatment with tPA (on the control arm 2 hours, on the intervention arm variable > 2 hours)

Secondary Outcomes (5)

• Efficiency - Short therm: hemodynamic stabilization

  36 hours after treatment

• Efficiency - Short therm: significant regression or absence of embolus mass on post treatment pulmonary angio CT scan

  24 hours after treatment

• Efficiency - Long therm: further improvement on pulmonary CT scan

  One month after the treatment

• Efficiency - Long therm: absence of right hearth failure on echocardiography

  One year after the treatment

• Efficiency - Long therm: improvement on 6 minutes walking test

  One year after the treatment

Study Arms (2)

Conventional thrombolysis group

ACTIVE COMPARATOR

A fixed dose of rtPA will be delivered, preferably with coagulation monitoring. The rtPA dose is 0.6 mg/kg over 15 minutes (with a maximum dose of 50 mg) for circulatory collapse, and 100 mg over 2 hours for circulatory instability that persists despite circulatory support

Drug: Alteplase Injectable Product

ClotPro-controlled variable dose of thrombolytic treatment.

EXPERIMENTAL

A variable dose will be delivered, according to ClotPro EX, IN, AP, FIB, ECA, RVV, TPA results. The starting rtPA dose is 0.15-0.04 mg/kg in bolus, the starting maintaining dose for the first lysis hour the same. ClotPro tests is made in every 1 h treatment. The maintaining rtPA dose if it is needed, will be increased, till EX, IN, ECA efficient lysis could be detected. On the other hand the reduction of the maintaining dose was permitted based on FIB MCF alarming decline. The thrombolysis treatment is stopped if the circulatory instability and/or circulatory support ceased. Based on FIB MCF results fibrinogen concentrate coadministration on safety reason is permitted.

Drug: Alteplase Injectable Product

Interventions

Alteplase Injectable Product DRUG

The 2019 ESC guideline for the diagnosis and management of acute pulmonary embolism (PE) recommended thrombolytic therapy only in high-risk PE cases because of the bleeding risk. The most often used drug for thrombolysis is the rtPA and the recommended dose is 100 mg over two hours. According to the literature, the risk of major haemorrhage is 10-13% and fatal or intracranial bleeding is 1.7-3.6% among patients receiving thrombolysis.

ClotPro-controlled variable dose of thrombolytic treatment.; Conventional thrombolysis group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pulmonary embolism confirmed by CT angiography of the chest, and planned systemic thrombolysis, taking into account the following:
• For indications based on circulatory collapse or circulatory instability that persists despite circulatory support, a fixed dose will be delivered, preferably with coagulation monitoring. The rtPA dose is 0.6 mg/kg over 15 minutes (with a maximum dose of 50 mg) for circulatory collapse, and 100 mg over 2 hours for circulatory instability that persists despite circulatory support.
• Otherwise, a regime relevant to our study is followed in the following cases in the individuals randomised to the study treatment group:
• Haemodynamic instability resolved through inotropic and/or vasopressor therapy, or
• In the event of right heart strain confirmed by echocardiography, and elevated cardiac biomarker (hs Troponin-T/NT-proBNP) in a haemodynamically stable patient, the regime to be followed will be determined by the monitoring results.

You may not qualify if:

• Failure to obtain informed consent from the patient (or from the closest relative of an incapacitated patient).
• Coagulation tests included in the study protocol cannot be performed for any technical reason or samples cannot be collected.
• Patients \<18 years of age at the onset of pulmonary embolism.
• Pregnancy.
• The following risk factors are known or currently present in the patient:
• Haemorrhagic stroke at any time in the medical history
• Major trauma or head injury within the last three weeks
• Incorrigible bleeding abnormality
• Active bleeding that cannot be attenuated
• Therapy refractory hypertension
• Infective endocarditis
• Patients lacking legal competence and the guardian or closest relative cannot be contacted.

Sponsors & Collaborators

• Semmelweis University: lead

Study Sites (1)

Semmelweis University Department of Anesthesiology and Intensive Therapy

Budapest, 1082, Hungary

Location

Related Publications (9)

• Zatroch I, Dinya E, Fazakas J. New under the sun: ClotPro's ECA-test detects hyperfibrinolysis in a higher number of patients, more frequently and 9 min earlier. Blood Coagul Fibrinolysis. 2023 Mar 1;34(2):99-104. doi: 10.1097/MBC.0000000000001185. Epub 2022 Dec 15.

  PMID: 36519572 BACKGROUND

• Konstantinides SV, Meyer G, Becattini C, Bueno H, Geersing GJ, Harjola VP, Huisman MV, Humbert M, Jennings CS, Jimenez D, Kucher N, Lang IM, Lankeit M, Lorusso R, Mazzolai L, Meneveau N, Ni Ainle F, Prandoni P, Pruszczyk P, Righini M, Torbicki A, Van Belle E, Zamorano JL; ESC Scientific Document Group. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J. 2020 Jan 21;41(4):543-603. doi: 10.1093/eurheartj/ehz405. No abstract available.

  PMID: 31504429 BACKGROUND

• Weinstein T, Deshwal H, Brosnahan SB. Advanced management of intermediate-high risk pulmonary embolism. Crit Care. 2021 Aug 31;25(1):311. doi: 10.1186/s13054-021-03679-2.

  PMID: 34461959 BACKGROUND

• Meyer G, Vicaut E, Danays T, Agnelli G, Becattini C, Beyer-Westendorf J, Bluhmki E, Bouvaist H, Brenner B, Couturaud F, Dellas C, Empen K, Franca A, Galie N, Geibel A, Goldhaber SZ, Jimenez D, Kozak M, Kupatt C, Kucher N, Lang IM, Lankeit M, Meneveau N, Pacouret G, Palazzini M, Petris A, Pruszczyk P, Rugolotto M, Salvi A, Schellong S, Sebbane M, Sobkowicz B, Stefanovic BS, Thiele H, Torbicki A, Verschuren F, Konstantinides SV; PEITHO Investigators. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med. 2014 Apr 10;370(15):1402-11. doi: 10.1056/NEJMoa1302097.

  PMID: 24716681 BACKGROUND

• Meneveau N, Seronde MF, Blonde MC, Legalery P, Didier-Petit K, Briand F, Caulfield F, Schiele F, Bernard Y, Bassand JP. Management of unsuccessful thrombolysis in acute massive pulmonary embolism. Chest. 2006 Apr;129(4):1043-50. doi: 10.1378/chest.129.4.1043.

  PMID: 16608956 BACKGROUND

• Hoffman M. A cell-based model of coagulation and the role of factor VIIa. Blood Rev. 2003 Sep;17 Suppl 1:S1-5. doi: 10.1016/s0268-960x(03)90000-2.

  PMID: 14697207 BACKGROUND

• Zatroch I, Smudla A, Babik B, Tanczos K, Kobori L, Szabo Z, Fazakas J. [Procoagulation, hypercoagulation and fibrinolytic "shut down" detected with ClotPro(R) viscoelastic tests in COVID-19 patients]. Orv Hetil. 2020 May;161(22):899-907. doi: 10.1556/650.2020.31870. Hungarian.

  PMID: 32453702 BACKGROUND

• Bachler M, Bosch J, Sturzel DP, Hell T, Giebl A, Strohle M, Klein SJ, Schafer V, Lehner GF, Joannidis M, Thome C, Fries D. Impaired fibrinolysis in critically ill COVID-19 patients. Br J Anaesth. 2021 Mar;126(3):590-598. doi: 10.1016/j.bja.2020.12.010. Epub 2020 Dec 9.

  PMID: 33422287 BACKGROUND

• Actilyse powder and solvent SmPC 12/09/2021, NIPN: https://ogyei.gov.hu/gyogyszeradatbazis.

  BACKGROUND

MeSH Terms

Conditions

Hemorrhage

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: October 24, 2024
• First Posted: October 31, 2024
• Study Start: December 17, 2021
• Primary Completion: October 24, 2024
• Study Completion: October 24, 2024
• Last Updated: October 31, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

HU (1)