Comparison of Different TRansesophageal Echocardiography Guided thrOmbolytic Regimens for prosthetIc vAlve Thrombosis

Study Overview
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Brief Summary
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Despite high mortality and morbidity, the best treatment strategies for prosthetic valve thrombosis (PVT) have been controversial. In this study the investigators wanted to identify the most effective and safe regimen among different thrombolytic strategies.Transesophageal echocardiography (TEE) guided thrombolytic treatment was administered to 182 consecutive patients with PVT in 220 different episodes (156 women, mean age 43.2±13.06 years) between 1993 and 2009. These regimens included rapid streptokinase (Group I, 16 episodes), slow streptokinase (Group II, 41 episodes), high dose (100 mg) tissue plasminogen activator (t-PA) (Group III, 12 episodes), half-dose (50 mg) slow infusion (6-hours) of t-PA without bolus (Group IV, 27 episodes), and low dose (25 mg) and slow infusion (6-hours) of t-PA without bolus (Group V, 124 episodes). The study endpoints were thrombolytic success and in-hospital mortality and non-fatal complication rates.

Detailed Description
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One hundred and eighty two consecutive in-hospital patients with 220 episodes of PVT between 1993 and 2009 were included in the study. The patients were enrolled after informed consent if there was no contraindication, to thrombolysis. The study was approved by the local Ethics Board. The patient demographics, past medical history, date of the operation, type and make of the prosthetic valve, rhythm disorders, aspirin use, NYHA functional capacity, leading symptoms and international normalization ratio (INR) values at the time of admission were prospectively entered into a database.The diagnosis of PVT was verified each time by transesophageal echocardiography (TEE) when a patient was admitted with thromboembolism or persistently low INR for the preceding consecutive 3 months and when a transthoracic echocardiography (TTE) documented prosthetic valve dysfunction or thrombus. All patients underwent TTE and TEE examination before and after the thrombolysis sessions. The cross sectional area and the longest diameter of the thrombus were measured on TEE recordings

Official Title
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Comparison of Different TRansesophageal Echocardiography Guided thrOmbolytic Regimens for prosthetIc vAlve Thrombosis

Conditions
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Prosthetic Valve Thrombosis

Intervention / Treatment
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* Drug: Streptokinase
* Drug: Streptokinase
* Drug: Tissue plasminogen activator
* Drug: Tissue Plasminogen Activator
* Drug: Tissue Plasminogen Activator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with prosthetic valve thrombosis Exclusion Criteria: Large left atrial thrombus Recent (<3 weeks) ischemic stroke Hemorrhagic stroke Early (<4 days) postoperative period Traumatic accident <4 weeks Bleeding diathesis † İntracranial mass Active internal bleed Aortic dissection
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: rapid streptokinase<br>3-hour infusion of 1.5 million units of streptokinase (16 patients, 16 episodes), repeat once 24 hours later if needed (maximum total dose 3 million units). | Drug: Streptokinase<br>* 3-hour infusion of 1.5 million units of streptokinase (16 patients, 16 episodes), repeat once 24 hours later if needed (maximum total dose 3 million units)<br>* Other names: Streptase;|
| Active Comparator: high dose tpa<br>5-hour infusion of 90 mg t-PA(Tissue plasminogen activator) after 10 mg bolus (10 patients, 12 episodes), repeat once 24 hours later if needed (maximum total dose 200 mg) | Drug: Tissue plasminogen activator<br>* 5-hour infusion of 90 mg t-PA (Tissue plasminogen activator) after 10 mg bolus (10 patients, 12 episodes), repeat once 24 hours later if needed (maximum total dose 200 mg)<br>* Other names: ACTILYSE;|
| Active Comparator: slow streptokinase<br>24-hour infusion of 1.5 million units of streptokinase (41 patients, 41 episodes), repeat once 24 hours later if needed (maximum total dose 3 million units). | Drug: Streptokinase<br>* 24-hour infusion of 1.5 million units of streptokinase (41 patients, 41 episodes), repeat once 24 hours later if needed (maximum total dose 3 million units).<br>* Other names: Streptase;|
| Active Comparator: half-dose slow infusion tpa<br>6-hour infusion of 50 mg t-PA (Tissue plasminogen activator) without bolus (27 patients, 27 episodes), repeat once 24 hours later up to 3 times if needed (maximum total dose 150 mg). | Drug: Tissue Plasminogen Activator<br>* 6-hour infusion of 50 mg t-PA (Tissue plasminogen activator) without bolus (27 patients, 27 episodes), repeat once 24 hours later up to 3 times if needed (maximum total dose 150 mg).<br>* Other names: ACTILYSE;|
| Active Comparator: low dose slow infusion tpa<br>6-hour infusion of 25 mg t-PA(Tissue plasminogen activator) without bolus (108 patients, 124 episodes), repeat once 24 hours later up to 6 times if needed (maximum total dose 150 mg). | Drug: Tissue Plasminogen Activator<br>* 6-hour infusion of 25 mg t-PA (Tissue plasminogen activator) without bolus (108 patients, 124 episodes), repeat once 24 hours later up to 6 times if needed (maximum total dose 150 mg).<br>* Other names: ACTILYSE;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Thrombolytic success | In the absence of fatal or nonfatal major complications; Obstructive thrombus: Doppler documentation of the resolution of increased gradient and decreased valve area. Clinical improvement in symptoms. Reduction by ≥75% in major diameter or area of the thrombus. Complete success was defined when all 3 criteria were met and partial success was defined as less than 3. Nonobstrucive thrombus: Complete success: ≥75% reduction in thrombus area. Partial success: 50%-75% reduction in thrombus area. | 24 hours | 
| Non-fatal complication rates | Nonfatal major complication: Ischemic stroke, intracranial hemorrhage, embolism (coronary or peripheral), bleeding requiring transfusion. Nonfatal minor complication: Bleeding without need for transfusion, TIA. | participants will be followed for the duration of hospital stay, an expected average of 3 weeks | 
| In-hospital mortality | All cause in-hospital mortality. | participants will be followed for the duration of hospital stay, an expected average of 3 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tPA, Prosthetic valve, thrombosis, TROIA, TEE