Surgery Versus Fibrinolytic Therapy for Left-sided Prosthetic Heart Valve Thrombosis (SAFE-PVT)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified July 2012 by All India Institute of Medical Sciences, New Delhi
Sponsor:
Information provided by (Responsible Party):
Dr Ganesan Karthikeyan, All India Institute of Medical Sciences, New Delhi
ClinicalTrials.gov Identifier:
NCT01641549
First received: July 10, 2012
Last updated: July 16, 2012
Last verified: July 2012
  Purpose

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.


Condition Intervention Phase
Left-sided Prosthetic Heart Valve Thrombosis
Procedure: Emergency surgery
Drug: Fibrinolytic therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Surgery Compared to Fibrinolytic Therapy for Symptomatic Patients With Left-sided Prosthetic Heart Valve Thrombosis

Resource links provided by NLM:


Further study details as provided by All India Institute of Medical Sciences, New Delhi:

Primary Outcome Measures:
  • Complete clinical response [ Time Frame: In-hospital, average of 10 days ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Death, stroke, major bleeding, or non-CNS systemic embolism [ Time Frame: In-hospital, average of 10 days ] [ Designated as safety issue: Yes ]
    A composite of in-hospital death, stroke, major bleeding or non-CNS systemic embolism.

  • Death, recurrent PVT, stroke or non-CNS systemic embolism or persistent abnormal valve function [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    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)


Estimated Enrollment: 150
Study Start Date: January 2013
Estimated Study Completion Date: January 2017
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Emergency surgery
Emergency surgery (valve replacement or thrombectomy)
Procedure: Emergency surgery
Emergency surgery (valve replacement or thrombectomy)
Other Name: Redo valve replacement
Active Comparator: Fibrinolytic therapy
Streptokinase (SK) at a dose of 0.25MU over 30 minutes followed by a 0.1MU/ hour infusion, or other fibrinolytic agent
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
Other Name: Thrombolytic therapy

Detailed 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

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01641549

Contacts
Contact: Ganesan Karthikeyan, MD, DM, MSc +91-11-26594464 karthik2010@gmail.com

Locations
India
Departments of cardiology and Cardiovascular Surgery, All India Institute of Medical Sciences Not yet recruiting
New Delhi, Delhi, India, 110029
Contact: Ganesan Karthikeyan, MD, DM, MSc    +91-11-26594464    karthik2010@gmail.com   
Principal Investigator: Ganesan Karthikeyan, MD, DM, MSc         
Sponsors and Collaborators
All India Institute of Medical Sciences, New Delhi
Investigators
Principal Investigator: Ganesan Karthikeyan, MD, DM, MSc All India Institute of Medical Sciences, New Delhi
  More Information

No publications provided

Responsible Party: Dr Ganesan Karthikeyan, Additional Professor of Cardiology, All India Institute of Medical Sciences, New Delhi
ClinicalTrials.gov Identifier: NCT01641549     History of Changes
Other Study ID Numbers: Version 1.01
Study First Received: July 10, 2012
Last Updated: July 16, 2012
Health Authority: India: Ministry of Health

Keywords provided by All India Institute of Medical Sciences, New Delhi:
Prosthetic valve thrombosis
Fibrinolytic therapy
Emergency surgery

Additional relevant MeSH terms:
Thrombosis
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Hematologic Agents

ClinicalTrials.gov processed this record on August 18, 2014