Left-sided Prosthetic Heart Valve ThrombosisPhase 3SAFE-PVTNCT01641549
Surgery Versus Fibrinolytic Therapy for Left-sided Prosthetic Heart Valve Thrombosis
A Phase 3 study testing Emergency surgery and Fibrinolytic therapy in people with Left-sided Prosthetic Heart Valve Thrombosis, run by All India Institute of Medical Sciences at 1 site in India.
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… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Left-sided Prosthetic Heart Valve Thrombosis
- What is being tested?
- Emergency surgery and Fibrinolytic therapy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 115 participants
- Where
- 1 siteIndia
- Study dates
- Apr 2017to Mar 2019
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All patients over 18 years of age with recent-onset (≤2 weeks), objectively diagnosed, symptomatic (NYHA class II-IV) left-sided prosthetic valve dysfunction
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
India1 site
Departments of cardiology and Cardiovascular Surgery, All India Institute of Medical Sciences
New Delhi, National Capital Territory of Delhi, 110029
Ganesan Karthikeyan, MD, DM, MSc, +91-11-26594464, karthik2010@gmail.com
Ganesan Karthikeyan, MD, DM, MSc
About this study
Official title: Surgery Compared to Fibrinolytic Therapy for Symptomatic Patients With Left-sided Prosthetic Heart Valve Thrombosis
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.
Read the 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
- Being tested
- Emergency surgery, Fibrinolytic therapy
- Keywords
- Prosthetic valve thrombosis, Fibrinolytic therapy, Emergency surgery
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Emergency surgeryProcedure or surgery
Also called Redo valve replacement
Emergency surgery (valve replacement or thrombectomy)
Fibrinolytic therapyDrug
Also called Thrombolytic 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
| Study group | Role | What they receive |
|---|---|---|
| Emergency surgery | Experimental | Emergency surgery (valve replacement or thrombectomy) Receives: Procedure: Emergency surgery |
| Fibrinolytic therapy | Active comparator | Streptokinase (SK) at a dose of 0.25MU over 30 minutes followed by a 0.1MU/ hour infusion, or other fibrinolytic agent Receives: Drug: Fibrinolytic therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: In-hospital, average of 10 days
Secondary outcomes (2)
Death, stroke, major bleeding, or non-CNS systemic embolism
A composite of in-hospital death, stroke, major bleeding or non-CNS systemic embolism.
Measured: In-hospital, average of 10 days
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)
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2012 (estimated)
- Study startApr 2017 (estimated)
- Primary completionMar 2019 (estimated)
- Study completionMar 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Left-sided Prosthetic Heart Valve ThrombosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 115 participants (estimated)
Sponsor and investigators
- Lead sponsor
- All India Institute of Medical Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr Ganesan Karthikeyan, All India Institute of Medical Sciences
- Investigators
- Ganesan Karthikeyan, MD, DM, MSc, Principal investigator, All India Institute of Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01641549
- Sponsor's protocol ID
- Version 1.01
- Acronym
- SAFE-PVT
- Status last verified
- Mar 2017
- First submitted
- 10 Jul 2012
- Last updated
- 10 Mar 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Surgery Compared to Fibrinolytic Therapy for Symptomatic Patients With Left-sided Prosthetic Heart Valve Thrombosis
- ClinicalTrials.gov ID
- NCT01641549
- Acronym / sponsor ID
- SAFE-PVT / Version 1.01
- Keywords
- Prosthetic valve thrombosis, Fibrinolytic therapy, Emergency surgery
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 115 participants (estimated)
- Lead sponsor
- All India Institute of Medical SciencesUniversity, hospital or other
- Study start
- Apr 2017 (estimated)
- Primary completion
- Mar 2019 (estimated)
- Study completion
- Mar 2019 (estimated)
- First posted
- 17 Jul 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Emergency surgery | Experimental | Procedure: Emergency surgeryEmergency surgery (valve replacement or thrombectomy) |
| Fibrinolytic therapy | Active comparator | Drug: Fibrinolytic therapyStreptokinase (SK) at a dose of 0.25MU over 30 minutes followed by a 0.1MU/ hour infusion, or other fibrinolytic agent |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- All patients over 18 years of age with recent-onset (≤2 weeks), objectively diagnosed, symptomatic (NYHA class II-IV) left-sided prosthetic valve dysfunction
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Emergency surgeryAlso: Redo valve replacementEmergency surgery (valve replacement or thrombectomy) | Procedure or surgery | Emergency surgery |
| Fibrinolytic therapyAlso: Thrombolytic therapyStreptokinase (SK) at a dose of 0.25MU over 30 minutes followed by a 0.1MU/ hour infusion, or other fibrinolytic agent at standard doses | Drug | Fibrinolytic therapy |
Primary outcome
Complete clinical response
Time frame: In-hospital, average of 10 days
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.
2 secondary outcomes
Death, stroke, major bleeding, or non-CNS systemic embolism
Time frame: In-hospital, average of 10 days
Death, recurrent PVT, stroke or non-CNS systemic embolism or persistent abnormal valve function
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2017.
- Individual participant dataSharing planned: Undecided
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ganesan Karthikeyan, MD, DM, MSc principal investigator
All India Institute of Medical Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Emergency surgery and Fibrinolytic therapy in people with Left-sided Prosthetic Heart Valve Thrombosis, run by All India Institute of Medical Sciences at 1 site in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 10 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ganesan Karthikeyan, MD, DM, MSc (+91-11-26594464, karthik2010@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete clinical response (time frame: In-hospital, average of 10 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2017.