Pulmonary Embolism Subacute MassiveNCT06667882
Safe Delivery of Thrombolytic Treatment for Pulmonary Embolism Using ClotPro® Viscoelastic Tests
A study testing Alteplase Injectable Product in people with Pulmonary Embolism Subacute Massive and Complication of Treatment, run by Semmelweis University at 1 site in Hungary.
Trial summary
The aim of this work was to reduce the bleeding risk during thrombolysis using the viscoelastic blood coagulation tests. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pulmonary Embolism Subacute Massive, Complication of Treatment, Fibrinolysis; Hemorrhage
- What is being tested?
- Alteplase Injectable Product
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteHungary
- Study dates
- 17 Dec 2021to 24 Oct 2024
- 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
- 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.
Who cannot join
- 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
Show all 12Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
Hungary1 site
Semmelweis University Department of Anesthesiology and Intensive Therapy
Budapest, 1082
About this study
The aim of this work was to reduce the bleeding risk during thrombolysis using the viscoelastic blood coagulation tests.
Read the detailed description
Patient data The patients' age, body measurements, general and coagulation-related medical history, SARS-COV2 status, APACHE-II, frailty score will be recorded.
Sampling times and examinations
The following considerations will be taken into account in the course of examining and providing care to the patients:
Imaging procedures:
CT angiography of the chest To confirm embolism and the results of lysis 12 to 24 hours after it is completed mandatory Echocardiography Right ventricle diameter mandatory views to be recorded: TAPSE mandatory parasternal longitudinal section IVC minimum and maximum diameter mandatory parasternal basal cross-section extent of tricuspid regurgitation mandatory apical 4 chamber estimated APsys mandatory subcostal 4 chamber D sign? mandatory IVC McConnel sign? optional 60/60 sign optional right heart thrombus optional Tricuspid annulus with reduced S' (<9.5 cm/s) tissue doppler optional Lower limb Doppler ultrasound Search for the origin of thromboembolism, preferably prior to lysis optional Table 2: Summary of the imaging procedures required for the study The condition for enrolment into the study is PE confirmed by CT angiography of the chest, with haemodynamic impact confirmed by echocardiography; the recording of the test in the IMPAX system is also a requirement. To assess the effectiveness of thrombolysis, echocardiography must be repeated after the lysis is completed, and then 12 to 24 hours later; the same is true for long-term follow-up.
Blood analyses:
Laboratory tests blood type + antibody screening mandatory blood count mandatory INR mandatory aPTI mandatory D-dimer mandatory fibrinogen mandatory Troponin T mandatory NT-proBNP mandatory creatinine mandatory urea mandatory electrolytes (Na+; K+; Ca2+ (t/ion); Mg2+; Cl-, phosphate) mandatory liver function (AST, ALT, LDH) mandatory Blood gases pH; pO2; pCO2 mandatory HCO3-; BE mandatory hgb mandatory Na+; K+; Ca2+; Cl- mandatory blood glucose mandatory lactate mandatory
Table 3: Summary of the laboratory and point-of-care blood tests required for the study The above lab parameters are planned to be obtained upon enrolment of a patient. Also, in addition to regular blood gas testing during the treatment, targeted testing for coagulation parameters and factors might be necessary.
Invasive interventions:
Arterial cannulation invasive pressure monitoring; pressurised infusion without heparin! mandatory PVC at least one, but preferably two, minimum G18 mandatory CVC only if vasopressor must be delivered; giving dobutamine to increase inotropy is not in itself an indication for a CVC! optional bladder catheter indication should be considered; if in doubt, should be inserted before the start of lysis optional endotracheal tube only for an indication not associated with pulmonary embolism optional Table 4: Considerations for the invasive interventions required for the study
Study phase and follow-up The study period is expected to last from 1 October 2021 to 31 December 2024. Follow-up (subject to a separate consent from the patients) will take place 1, 3 and 12 months after the thrombolysis and is planned to include quality of life questionnaires (EuroQOL -5D-5L), assessment of physical capacity (6MW, or, if unfeasible, Timed Up\&Go test), echocardiography, ClotPro and blood gas testing.
Methodology and organisation of the study Potential recruits are the patients of Semmelweis University with relevant impact on circulation (high-risk or intermediate to high-risk categories), whose PE is confirmed by CT angiography of the chest. Patients may come from the Emergency Care Unit or may be hospitalised patients from another department. The patient will then be admitted to the Anaesthesiology and Intensive Therapy Clinic and receive care there until stabilised.
Instable patients who are enrolled will all be administered a fixed dose (100 mg/h) (see the section 'Inclusion criteria'). High risk or intermediate-high risk patients who can be stabilised will be randomised and then receive either a fixed dose (100 mg/2h) or a ClotPro-controlled variable dose of thrombolytic treatment.
Coagulation tests
ClotPro tests are planned before and regularly after the start of treatment: EX, IN, FIB, TPA, AP, RVV and ECA tests will be required.
Statistical methods Statistical analyses will be performed by Social Sciences software (SPSS; SPSS Inc, Chicago, Illinois, USA).
Continuous and discrete variables will be analysed by independent samples t tests (two categories) and one-way analyses of variance (one-way ANOVA; more categories), respectively. Two continuous variables will be compared by Spearman's rank correlation test. Discrete variables will be tested by Pearson's Chi squared test. Ordinary variables will be compared by Mann-Whitney U test or Kruskal-Wallis test. For multivariate analyses, logistic regression models will be generated.
Significance level will be set to 5% (p ≤ 0.05).
- Being tested
- Alteplase Injectable Product
- Medical subject headings
- Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Alteplase Injectable ProductDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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. Receives: Drug: Alteplase Injectable Product |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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
Measured: 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
absence of circulatory shock/circulatory support ceased
Measured: 36 hours after treatment
Efficiency - Short therm: significant regression or absence of embolus mass on post treatment pulmonary angio CT scan
Measured: 24 hours after treatment
Efficiency - Long therm: further improvement on pulmonary CT scan
Long term: further improvement on pulmonary CT scan
Measured: One month after the treatment
Efficiency - Long therm: absence of right hearth failure on echocardiography
Absence of right heart failure on echocardiography:
- no D-sign AND
- basal right ventricle/left ventricle ratio < 1 AND
- tricuspidal annular plain systolic excursion > 16 mm AND
- Tissue Doppler Imaging: peak systolic velocity of tricuspid annulus > 9.5 cm/s
Measured: One year after the treatment
Efficiency - Long therm: improvement on 6 minutes walking test
Long term: improvement on 6 minutes walking test. The measured parameters:
- 6 minutes walking test distance ( 6MWD - in meter)
- 6MWD/predicted 6MWD (%)
- distance desaturation product (DSP - m%)
Measured: One year after the treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2024
- Study start17 Dec 2021
- Primary completion24 Oct 2024
- Study completion24 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Pulmonary Embolism Subacute MassiveStudies of the same condition, open and under way.
- More trials run by Semmelweis UniversityThe sponsor's other registered studies.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Semmelweis University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Janos Fazakas MD, PhD, Semmelweis University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06667882
- Sponsor's protocol ID
- 65187-5/2021/EÜIG
- Status last verified
- Oct 2024
- First submitted
- 24 Oct 2024
- Last updated
- 31 Oct 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 36519572Konstantinides 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.
PubMed 31504429Weinstein 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.
PubMed 34461959Meyer 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.
PubMed 24716681Meneveau 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.
PubMed 16608956Hoffman 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.
PubMed 14697207Zatroch 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.
PubMed 32453702Bachler 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.
PubMed 33422287Actilyse powder and solvent SmPC 12/09/2021, NIPN: https://ogyei.gov.hu/gyogyszeradatbazis.
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safe Delivery of Thrombolytic Treatment for Pulmonary Embolism Using ClotPro® Viscoelastic Tests
- ClinicalTrials.gov ID
- NCT06667882
- Acronym / sponsor ID
- 65187-5/2021/EÜIG
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Semmelweis UniversityUniversity, hospital or other
- Study start
- 17 Dec 2021 (actual)
- Primary completion
- 24 Oct 2024 (actual)
- Study completion
- 24 Oct 2024 (actual)
- First posted
- 31 Oct 2024 (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 aim of this work was to reduce the bleeding risk during thrombolysis using the viscoelastic blood coagulation tests.
Detailed description
Patient data The patients' age, body measurements, general and coagulation-related medical history, SARS-COV2 status, APACHE-II, frailty score will be recorded.
Sampling times and examinations
The following considerations will be taken into account in the course of examining and providing care to the patients:
Imaging procedures:
CT angiography of the chest To confirm embolism and the results of lysis 12 to 24 hours after it is completed mandatory Echocardiography Right ventricle diameter mandatory views to be recorded: TAPSE mandatory parasternal longitudinal section IVC minimum and maximum diameter mandatory parasternal basal cross-section extent of tricuspid regurgitation mandatory apical 4 chamber estimated APsys mandatory subcostal 4 chamber D sign? mandatory IVC McConnel sign? optional 60/60 sign optional right heart thrombus optional Tricuspid annulus with reduced S' (<9.5 cm/s) tissue doppler optional Lower limb Doppler ultrasound Search for the origin of thromboembolism, preferably prior to lysis optional Table 2: Summary of the imaging procedures required for the study The condition for enrolment into the study is PE confirmed by CT angiography of the chest, with haemodynamic impact confirmed by echocardiography; the recording of the test in the IMPAX system is also a requirement. To assess the effectiveness of thrombolysis, echocardiography must be repeated after the lysis is completed, and then 12 to 24 hours later; the same is true for long-term follow-up.
Blood analyses:
Laboratory tests blood type + antibody screening mandatory blood count mandatory INR mandatory aPTI mandatory D-dimer mandatory fibrinogen mandatory Troponin T mandatory NT-proBNP mandatory creatinine mandatory urea mandatory electrolytes (Na+; K+; Ca2+ (t/ion); Mg2+; Cl-, phosphate) mandatory liver function (AST, ALT, LDH) mandatory Blood gases pH; pO2; pCO2 mandatory HCO3-; BE mandatory hgb mandatory Na+; K+; Ca2+; Cl- mandatory blood glucose mandatory lactate mandatory
Table 3: Summary of the laboratory and point-of-care blood tests required for the study The above lab parameters are planned to be obtained upon enrolment of a patient. Also, in addition to regular blood gas testing during the treatment, targeted testing for coagulation parameters and factors might be necessary.
Invasive interventions:
Arterial cannulation invasive pressure monitoring; pressurised infusion without heparin! mandatory PVC at least one, but preferably two, minimum G18 mandatory CVC only if vasopressor must be delivered; giving dobutamine to increase inotropy is not in itself an indication for a CVC! optional bladder catheter indication should be considered; if in doubt, should be inserted before the start of lysis optional endotracheal tube only for an indication not associated with pulmonary embolism optional Table 4: Considerations for the invasive interventions required for the study
Study phase and follow-up The study period is expected to last from 1 October 2021 to 31 December 2024. Follow-up (subject to a separate consent from the patients) will take place 1, 3 and 12 months after the thrombolysis and is planned to include quality of life questionnaires (EuroQOL -5D-5L), assessment of physical capacity (6MW, or, if unfeasible, Timed Up\&Go test), echocardiography, ClotPro and blood gas testing.
Methodology and organisation of the study Potential recruits are the patients of Semmelweis University with relevant impact on circulation (high-risk or intermediate to high-risk categories), whose PE is confirmed by CT angiography of the chest. Patients may come from the Emergency Care Unit or may be hospitalised patients from another department. The patient will then be admitted to the Anaesthesiology and Intensive Therapy Clinic and receive care there until stabilised.
Instable patients who are enrolled will all be administered a fixed dose (100 mg/h) (see the section 'Inclusion criteria'). High risk or intermediate-high risk patients who can be stabilised will be randomised and then receive either a fixed dose (100 mg/2h) or a ClotPro-controlled variable dose of thrombolytic treatment.
Coagulation tests
ClotPro tests are planned before and regularly after the start of treatment: EX, IN, FIB, TPA, AP, RVV and ECA tests will be required.
Statistical methods Statistical analyses will be performed by Social Sciences software (SPSS; SPSS Inc, Chicago, Illinois, USA).
Continuous and discrete variables will be analysed by independent samples t tests (two categories) and one-way analyses of variance (one-way ANOVA; more categories), respectively. Two continuous variables will be compared by Spearman's rank correlation test. Discrete variables will be tested by Pearson's Chi squared test. Ordinary variables will be compared by Mann-Whitney U test or Kruskal-Wallis test. For multivariate analyses, logistic regression models will be generated.
Significance level will be set to 5% (p ≤ 0.05).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Conventional thrombolysis group | Active comparator | Drug: Alteplase Injectable ProductA 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 |
| ClotPro-controlled variable dose of thrombolytic treatment. | Experimental | Drug: Alteplase Injectable ProductA 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (12 listed)
- 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:
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 |
|---|---|---|
| Alteplase Injectable ProductThe 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. | Drug | ClotPro-controlled variable dose of thrombolytic treatment., Conventional thrombolysis group |
Primary outcome
Major, life threatening bleeding due to profuse bleeding
Time frame: during the treatment with tPA (on the control arm 2 hours, on the intervention arm variable > 2 hours)
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
Major, life threatening bleeding due to intracranial haemorrhage
Time frame: during the treatment with tPA (on the control arm 2 hours, on the intervention arm variable > 2 hours)
Intracranial hemorrhage - new onset of neurological symptoms
Minor bleeding: Haemoglobin reduction > 10g/l during the treatment
Time frame: during the treatment with tPA (on the control arm 2 hours, on the intervention arm variable > 2 hours)
Haemoglobin reduction > 10g/l, but less, than 30 g/l
5 secondary outcomes
Efficiency - Short therm: hemodynamic stabilization
Time frame: 36 hours after treatment
Efficiency - Short therm: significant regression or absence of embolus mass on post treatment pulmonary angio CT scan
Time frame: 24 hours after treatment
Efficiency - Long therm: further improvement on pulmonary CT scan
Time frame: One month after the treatment
Efficiency - Long therm: absence of right hearth failure on echocardiography
Time frame: One year after the treatment
Efficiency - Long therm: improvement on 6 minutes walking test
Time frame: One year after the treatment
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 31 Oct 2024.
- Background: PubMed 36519572Zatroch 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.
- Background: PubMed 31504429Konstantinides 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.
- Background: PubMed 34461959Weinstein 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.
- Background: PubMed 24716681Meyer 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.
- Background: PubMed 16608956Meneveau 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.
- Background: PubMed 14697207Hoffman 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.
- Background: PubMed 32453702Zatroch 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.
- Background: PubMed 33422287Bachler 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.
- BackgroundActilyse powder and solvent SmPC 12/09/2021, NIPN: https://ogyei.gov.hu/gyogyszeradatbazis.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Alteplase Injectable Product in people with Pulmonary Embolism Subacute Massive and Complication of Treatment, run by Semmelweis University at 1 site in Hungary.
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 5 inclusion and 12 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 31 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Hungary. 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?
Major, life threatening bleeding due to profuse bleeding (time frame: during the treatment with tPA (on the control arm 2 hours, on the intervention arm variable > 2 hours)). The study lists 3 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 NCT06667882, which also lists 9 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 31 Oct 2024.