Comparison of fast versus ultraslow infusion of thrombolytic in patients with mechanical prosthetic valve thrombosis- A randomized controlled trial

Comparison of fast versus ultraslow infusion of thrombolytic regimen in patients with mechanical prosthetic valve thrombosis

Two parallel groups randomized trial with blinded outcome assessment

The trial will be held in a hospital setting (Rajaie Cardiovascular Medical and Research center) on patients with mechanical prosthetic valve thrombosis . Patients will be randomized via central web based method into two interventional groups with two different thrombolytic regimen. Treating physician and patients will not be blinded. Thrombus resolution and degree of valve openingwill be evaluated by echocardiography after thrombolytic therapy. Also thrombolytic complication will be evaluated during hospitalization.

Inclusion criteria: provision of signed and dated informed consent form; patients with prosthetic mechanical valve thrombosis approved by echocardiography; men and women ≥ 18 year-old. Exclusion criteria: contraindication of thrombolytic therapy; dyspnea of functional class 4; thrombus size larger than 0.8 cm2.

In this study there are two interventional groups: first group: patients will receive fast thrombolytic regimen. Second group: patients will receive ultra slow thrombolytic regimen.

Degree of valve opening; thrombus size; clinical functional class; bleeding; thromboembolic complications

Randomization will be performed via permuted block randomization method. Allocation will be generated via a web based system and consequently concealment will be central using computer software. Unit of randomization will be individual patients and no stratification will be applied.

Background Thrombolysis is an alternative to surgery for mechanical prosthetic valve thrombosis (MPVT). Randomized clinical trials have yet to test safety and efficacy of a proposed ultraslow thrombolytic infusion regimen. Methods and Results This single-center, open-label, pilot randomized clinical trial randomized adult patients with acute obstructive MPVT to an ultraslow thrombolytic regimen (25 mg of recombinant tissue-type plasminogen activator [rtPA] infused in 25h) and a fast thrombolytic regimen (50 mg of rtPA infused in 6h). If thrombolysis failed, a repeated dose of 25 mg of rtPA for 6h was administered in both groups up to a cumulative dose of 150 mg or the occurrence of a complication. Primary outcome was a complete MPVT resolution (>75% fall in the obstructive gradient by transthoracic echocardiography, <10° limitation in opening and closing valve motion angles by fluoroscopy, and symptom improvement). Key safety outcome was a BARC type III or V major bleeding. Overall, 120 patients, including 63 (52.5%) women, at a mean age of 36.3±15.3 years, were randomized. Complete thrombolysis success was achieved in 51 patients (85.0%) in the ultraslow-regimen group and 47 patients (78.3%) in the fast-regimen group (OR, 1.58; 95% CI, 0.25 to 1.63; P = 0.34). One case of transient ischemic attack and 3 cases of intracranial hemorrhage (absolute risk difference, −12.5%; 95% CI, −23.1% to −1.0%; P = 0.04). were observed only in the fast-regimen group. Conclusions The ultraslow thrombolytic regimen conferred a high thrombosis resolution rate without major complications. Such findings should be replicated in more adequately powered trials (IRCT20181022041406N2).