Clinical trial NCT00232622: A Study Comparing a New Dosing Regimen of Clot-dissolving Drug for Mechanical Heart Valves Which Show Clots
Official title: A Prospective Randomized Trial of a Rapid Fibrinolytic Protocol for Left-sided Prosthetic Valve Thrombosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Prosthetic Valve Thrombosis
Keywords: Prosthetic valve thrombosis
Fibrinolysis
Streptokinase
Lead sponsor: All India Institute of Medical Sciences
Sponsor class: OTHER
First posted: 2005-10-05
Enrollment: 120
Sex: ALL
Minimum age (years): 12
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The optimal dosage and duration of administration of clot-dissolving medications for the treatment of patients with mechanical heart valves with clots is not known. We hypothesized that a large dose of the clot-dissolving medicine given initially (akin to the dose given in the treatment of heart attacks), might speed up the dissolution of the clot and rapidly restore the functioning of the mechanical heart valve.

Detailed description: The optimal fibrinolytic strategy for left sided prosthetic valve thrombosis (PVT) is not known. A large initial bolus dose of streptokinase (SK) might accelerate fibrinolysis and restore valve function more rapidly.

This is a prospective, randomized trial comparing 2 fibrinolytic protocols in a first episode of PVT. In the rapid fibrinolytic protocol (RFP) 1.5 MU of SK is given over 1 hour, followed if required by a 0.1 MU/h infusion. In the standard protocol (SP) 0.25 MU is given over 30 minutes, followed by an infusion of 0.1 MU/h. Serial echocardiography and fluoroscopy will be done to monitor therapy. The primary end point is the occurrence of a complete clinical response (CCR, complete hemodynamic response without any major complication). 58 patients are required in each arm for detecting a 30% difference with 80% power at α=0.05.

Eligibility criteria: Inclusion Criteria:

* First episode of left sided prosthetic valve thrombosis

Exclusion Criteria:

* Contraindication to thrombolysis
* Refusal to give informed consent
* Pregnant women
* age less than 12 years or more than 70 years
* previous treatment for prosthetic valve thrombosis

Primary outcomes:
measure: The occurrence of a complete clinical response (complete hemodynamic response as assessed by echocardiography and fluoroscopy, without any major complication)
timeFrame: In-hospital
Secondary outcomes:
measure: Death, Major bleeding and minor bleeding
timeFrame: In-hospital
Other outcomes:
Locations:
Study officials:
affiliation: Department of Cardiology, All India Institute of Medical Sciences
name: Ganesan Karthikeyan, MD, DM
role: PRINCIPAL_INVESTIGATOR
References:
citation: Karthikeyan G, Math RS, Mathew N, Shankar B, Kalaivani M, Singh S, Bahl VK, Hirsh J, Eikelboom JW. Accelerated infusion of streptokinase for the treatment of left-sided prosthetic valve thrombosis: a randomized controlled trial. Circulation. 2009 Sep 22;120(12):1108-14. doi: 10.1161/CIRCULATIONAHA.109.876706. Epub 2009 Sep 8.
citation: Karthikeyan G, Mathew N, Math RS, Devasenapathy N, Kothari SS, Bahl VK. Timing of adverse events during fibrinolytic therapy with streptokinase for left-sided prosthetic valve thrombosis. J Thromb Thrombolysis. 2011 Aug;32(2):146-9. doi: 10.1007/s11239-011-0579-4.
citation: Barwad P, Raheja A, Venkat R, Kothari SS, Bahl V, Karthikeyan G. High prevalence of silent brain infarction in patients presenting with mechanical heart valve thrombosis. Am J Cardiovasc Drugs. 2012 Oct 1;12(5):345-8. doi: 10.1007/BF03261843.