Surgery Versus Fibrinolytic Therapy for Left-sided Prosthetic Heart Valve Thrombosis

Left-sided Prosthetic Heart Valve Thrombosis Clinical Trial

— SAFE-PVT  

Official title:

Surgery Compared to Fibrinolytic Therapy for Symptomatic Patients With Left-sided Prosthetic Heart Valve Thrombosis

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT01641549
• Other study ID #: Version 1.01
• Status: Not yet recruiting
• Phase: Phase 3
• First received: July 10, 2012
• Last updated: March 8, 2017
• Start date: April 2017
• Est. completion date: March 2019

Study information

• Verified date: March 2017
• Source: All India Institute of Medical Sciences, New Delhi
• Contact: Ganesan Karthikeyan, MD, DM, MSc
• Phone: +91-11-26594464
• Email: karthik2010[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Malfunction of mechanical heart valves due to clot formation is a potentially devastating complication. It often results in heart failure, death or stroke. This condition occurs frequently in patients with mechanical valves in developing countries because they are unable to monitor and adjust the dose of blood thinning medications. The best treatment modality for the treatment of patients with this condition is not known. There is no reliable data from clinical trials to guide treatment and there are no firm guidelines. Treatment with clot-busting drugs is most commonly used because these drugs (e.g., streptokinase) are readily available, cheap, and easy to use. However, this treatment is associated with high rates of treatment-related side-effects (death, life-threatening bleeding and stroke). Moreover, some recent studies suggest that clot-busting drugs may not be as efficacious in restoring valve function, as previously believed. Emergency surgery is less often used because it is more expensive and the required facilities and manpower are not available at all times at all places. But there is evidence to suggest that surgery results in better success rates with a lower risk of bleeding and stroke. Well-designed prospective randomised trials (the "gold-standard" for reliable evidence) comparing the efficacy, safety and cost-effectiveness of the two modalities, are needed to help doctors in developing countries make informed decisions when treating patients with clotted mechanical heart valves. The investigators propose to perform a randomised controlled trial comparing emergency surgery with treatment with clot-busting agents in patients with clotted mechanical valves. The study will be conducted over 4 years at a single, university hospital in a developing country. This study will determine how often patients who are treated with surgery will be discharged from hospital, with completely restored valve function, without having suffered a stroke or life-threatening bleeding, when compared to those who received clot-busting drugs. The investigators will also find out which of the treatments is safe and cost-effective.

Description:

Left-sided prosthetic valve thrombosis (PVT) is a potentially devastating complication which can affect patients with mechanical heart valves. It occurs frequently in developing countries because of poor anticoagulation quality. The best modality for treating this condition is not known. Most of the available data is from retrospective studies and case series, and current guidelines are based largely on expert opinion. Therefore recommendations for treatment vary widely. Fibrinolytic therapy (FT) is the most commonly used treatment because fibrinolytic agents such as streptokinase are readily available, cheap, and easy to use. However, FT is associated with high rates of treatment-related adverse effects (death, major bleeding and stroke). Moreover, recent studies suggest that FT may not be as efficacious in restoring valve function, as previously believed. Emergency surgery is less often used because it is more expensive and the required facilities and manpower are not available at all times at all places. A systematic review and meta-analysis of the available literature that the investigators performed, suggests that surgery may result in better success rates with a lower risk of major bleeding, stroke and non-CNS systemic embolism. Evidence from well designed randomised controlled trials is needed to determine the optimal treatment of left-sided PVT. The investigators propose to do a single-centre, open-label, randomised controlled trial comparing emergency surgery with FT for the treatment of symptomatic patients with left-sided PVT. The primary outcome is the occurrence of a complete clinical response, defined as discharge from hospital with completely restored valve function, in the absence of stroke, major bleeding or non-CNS systemic embolism. The investigators will compare the safety of the two interventions and quality of life at discharge and at 1 year. The investigators will also assess the cost-effectiveness of surgery compared to FT from a societal perspective in the context of the Indian healthcare system

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 115
• Est. completion date: March 2019
• Est. primary completion date: March 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• All patients over 18 years of age with recent-onset (=2 weeks), objectively diagnosed, symptomatic (NYHA class II-IV) left-sided prosthetic valve dysfunction

Exclusion Criteria:

• Absolute contraindications to FT (any history of intracranial hemorrhage, active bleeding from any site, ischemic stroke in the preceding 3 months, left atrial thrombus on TTE)

• Pregnant patients

• Asymptomatic patients (incidentally detected valve thrombosis)

• Inability to obtain (or refusal to provide) informed consent

Related Conditions & MeSH terms

• Left-sided Prosthetic Heart Valve Thrombosis
• Thrombosis

Intervention

Procedure:
• Emergency surgery
Emergency surgery (valve replacement or thrombectomy)

Drug:
• Fibrinolytic therapy
Streptokinase (SK) at a dose of 0.25MU over 30 minutes followed by a 0.1MU/ hour infusion, or other fibrinolytic agent at standard doses

Locations

Country	Name	City	State
India	Departments of cardiology and Cardiovascular Surgery, All India Institute of Medical Sciences	New Delhi	Delhi

Sponsors (1)

Lead Sponsor	Collaborator
All India Institute of Medical Sciences, New Delhi

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete clinical response	The primary outcome is the occurrence of a complete clinical response, defined as discharge from hospital with completely restored valve function, in the absence of stroke, major bleeding or non-CNS systemic embolism.	In-hospital, average of 10 days
Secondary	Death, stroke, major bleeding, or non-CNS systemic embolism	A composite of in-hospital death, stroke, major bleeding or non-CNS systemic embolism.	In-hospital, average of 10 days
Secondary	Death, recurrent PVT, stroke or non-CNS systemic embolism or persistent abnormal valve function	A composite of death, recurrent PVT, stroke or non-CNS systemic embolism, and persistent abnormal valve function (or re-do surgery for persistent valve dysfunction)	1 year