Reduced Dose Thrombolytic in Intermediate/High Risk Pulmonary Thromboembolism

Sponsor

Ege University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05512702

Collaborator

(none)

100

Enrollment

Location

Anticipated Duration (Months)

4.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Pulmonary Embolism(PE) requires multidisciplinary approach as a highly morbid and mortal disease. This multidisciplinary approach creates clinical benefits in diagnostic and therapeutic process. And these benefits are pointed out in certain studies and guidelines. For these reasons, we established a Pulmonary Embolism Response Team (PERT) on 5 th November 2018 which is called as Ege Pulmonary Embolism Team (EGEPET) in our university.

In recent years, it is stated that the carefully use of thrombolytic in patients with intermediate-high risk PE based on early mortality classification. Some studies have reported that the use of thrombolytic may cause clinical benefits. But which used drug and which dose are not defined clearly yet.

After establishment of EGEPET, we observed that patients with intermediate-high risk PE more receive reduced dose thrombolytic than the pre-EGEPET period. And we aimed to compare treatment changes after and before the establishment of EGEPET. Also, we will compare initial reduced dose thrombolytic therapy after EGEPET with initial anticoagulation therapy before EGEPET (historical group) in terms of mortality and complication.

As the reduced dose thrombolytic, Alteplase 50 mg is used in our hospital. Low-molecular weight heparin (LMWH), standard heparin and rarely Fondaparinux are used for anticoagulation therapy. Low-molecular weight heparin is generally applied for treatment, in case there is no contraindication.

Our primary end-point is to assess 30-day mortality and secondary-end points are to detect in one year-mortality and complications. We will compare the mortality and complication rates in these groups.

N0 hypothesis; In the intermediate-high risk group diagnosed with PE, there is an increased mortality rate in the patients treated with half-dose thrombolytic (Alteplase 50 mg) than our historical group or the literature.

N1 hypothesis; In the intermediate-high risk group diagnosed with PE, there is no an increased mortality rate in the patients treated with half-dose thrombolytic (Alteplase 50 mg) than our historical group or the literature.

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Embolism	Drug: Tissue Plasminogen Activator, Alteplase Drug: Low-molecular weight heparin

Detailed Description

Pulmonary thromboembolism ranks 3rd among cardiovascular diseases in terms of mortality. Pulmonary Embolism (PE) is a challenging disease that requires rapid approach both in the diagnosis and treatment process. Due to the challenging nature of the disease, Pulmonary Embolism Response Teams (PERT) have emerged for quick intervention in patients with PE. In the management of PE, multidisciplinary approach that includes the branches of pulmonary diseases, cardiology, emergency medicine, cardiovascular surgery, anesthesiology and radiology provides clinical advantages. Therefore, we established a PERT that called Ege Pulmonary Embolism Team (EGEPET). EGEPET established on 5th of November 2018. This team contains specialists from Pulmonary Diseases, Cardiology, Emergency Medicine, Cardiovascular Surgery, Anesthesiology and Radiology Departments. EGEPET works during 7/24 as a response team. It has been stated in recent publications and pulmonary thromboembolism guidelines that the establishment of multidisciplinary study group which is similar to our group will be more effective in the diagnosis, treatment and follow-up processes of PE patients.

Specially, there are some different opinions for the treatment of Intermediate-High risk based on according to early mortality with PE patients. While some guidelines suggest initial anticoagulation treatment without thrombolytic treatment, some researchers state that thrombolytic treatment can be used in Intermediate-High risk patients. These researchers indicate that the careful use of thrombolytic can be improved in clinical situation of PE patients. The careful usage is meant to use reduced dose thrombolytic and to follow up the patients closely for bleeding complication.

In cases diagnosed with intermediate-high risk PE in related to early mortality, it has been seen that half-dose thrombolytics are given mostly in our daily life practice after EGEPET.

So, we planned to evaluate the mortality and morbidity rates in the patients who were diagnosed with pulmonary thromboembolism with intermediate-high risk in terms of early mortality and who received half-dose thrombolytics according to the result of the EGEPET consultation.

50 mg Alteplase is used as thrombolytic treatment and we use low-molecular weight heparin (LMWH), standard heparin and rarely Fondaparinux for initial anticoagulation treatment. Low-molecular weight heparin is generally applied for treatment, in case there is no contraindication.

This study is an observational drug study. Researchers of this study did not and will not intervene the treatment of patients. Treatment decision of the patients is decided by EGEPET physicians.

We will compare the patients diagnosed with intermediate-high risk PE who received reduced dose thrombolytic which the decision is made by EGEPET with the other patients who did not get thrombolytic treatment in terms of mortality and morbidity.

The other patient group with intermediate-high risk PE will be created from our historical data to prevent to selection bias. Because, EGEPET offers generally reduced dose thrombolytic in intermediate-high risk PE patients. Otherwise, patients having high bleeding scores (e.g. RIETE bleeding score), multiple and severe comorbidities or patients who are quite old generally receive only anticoagulation treatment.

The patients assessed our study were classed into three groups. All of the patients have PE and are stated into intermediate-high risk according to early mortality.

First group is prospective group, which contains patients recruited after approval of ethic committee of this study. Ethic committee was taken from both organization Ege University and The Ministry of Health-Türkiye.

Second group is retrospective group, which contains patients evaluated by EGEPET and received reduced dose thrombolytic treatment.

Third group is called as historical control group. This patients group were diagnosed and treated with anticoagulants not thrombolytic treatment before establishment of EGEPET.

First and second groups compose the thrombolytic group, third group create the anticoagulant group (control)

We are going to collect data (clinical, laboratory and radiological variables) of these patients to get detailed clinical information.

We will compare the thrombolytic group with anticoagulant group (control). Our primary end-point is to evaluate 30-day mortality and secondary-end point are to detect in one year-mortality and complications.

We will compare mortality and complication rates in both groups.

Study Design

Study Type:

Observational

Anticipated Enrollment :

100 participants

Observational Model:

Cohort

Time Perspective:

Other

Official Title:

Treatment Approach in Patients Diagnosed With Pulmonary Thromboembolism With Intermediate-High Risk Interms of Early Mortality After the Establisment of Ege Pulmonary Embolism Team

Actual Study Start Date :

Jun 3, 2022

Anticipated Primary Completion Date :

Jun 3, 2023

Anticipated Study Completion Date :

Jun 3, 2024

Arms and Interventions

Arm	Intervention/Treatment
Thrombolytic Treatment Group These are the patients with intermediate-high riskPE and consulted by EGEPET. They received reduced dose thrombolytic treatment.	Drug: Tissue Plasminogen Activator, Alteplase Reduced dose (50 mg) Alteplase is used for the patients in the thrombolytic treatment group.
Anticoagulation Treatment Group This group includes patients who diagnosed wit PE before the establishment of EGEPET. And these patients are classed into intermediate-high risk based on early mortality and received anticoagulation treatment, not thrombolytic treatment.	Drug: Low-molecular weight heparin Patients in the anticoagulation treatment group receive this treatment and do not receive thrombolytic treatment.

Arm

Intervention/Treatment

Thrombolytic Treatment Group

These are the patients with intermediate-high riskPE and consulted by EGEPET. They received reduced dose thrombolytic treatment.

Drug: Tissue Plasminogen Activator, Alteplase

Reduced dose (50 mg) Alteplase is used for the patients in the thrombolytic treatment group.

Anticoagulation Treatment Group

This group includes patients who diagnosed wit PE before the establishment of EGEPET. And these patients are classed into intermediate-high risk based on early mortality and received anticoagulation treatment, not thrombolytic treatment.

Drug: Low-molecular weight heparin

Patients in the anticoagulation treatment group receive this treatment and do not receive thrombolytic treatment.

Outcome Measures

Primary Outcome Measures

30 day Mortality [30 day after diagnosis of pulmonary tromboembolism]
Includes 30-day mortality and contains all causes of death.

Secondary Outcome Measures

1 year Mortality [1 year after diagnosis of pulmonary tromboembolism]
Includes 1 year mortality and contains all causes of death.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients which are in intermediate-high risk class ased on mortality in the ESC/ERS Pulmonary Embolism Risk Classification

Exclusion Criteria:

Unwillingness of patient to participate in the study
The case is in the intermediate-high risk class, but there is an unstable disease that will affect mortality due to malignancy or general medical condition.