Deep Vein ThrombosisNCT00789399
A Study of the Efficacy of Preventive Dosing of Fondaparinux Sodium Versus Placebo for the Prevention of Venous Thromboembolism (VTE) in Patients Undergoing Coronary Bypass Surgery Receiving Routine Mechanical Prophylaxis
A study testing Fondaparinux in people with Deep Vein Thrombosis and Coronary Artery Bypass Surgery, run by Prairie Education and Research Cooperative.
Trial summary
This trial is a prospective, single-center Phase II randomized study to demonstrate the superior efficacy of Fondaparinux Sodium subcutaneous injections in patients undergoing CABG surgery (isolated and redo isolated) versus treatment with placebo. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Deep Vein Thrombosis, Coronary Artery Bypass Surgery, Venous Thromboembolism
- What is being tested?
- Fondaparinux
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 78 participants
- Where
- No sites listed yet
- Study dates
- 19 Nov 2009to 21 Sep 2013
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Subject Inclusion Criteria In order to be enrolled in the study, subjects must meet all of the inclusion criteria as listed below.
- Consecutive patients undergoing isolated or redo isolated CABG
- Patients must provide written informed consent
- Patients must agree to comply with study procedures for the entire length of the study.
- Must be 18 years old or greater.
Subject Exclusion Criteria Any subject that meets any of the exclusion criteria listed below at baseline will be excluded from study participation.
- Patients with medical history that requires chronic anticoagulation with unfractionated heparin or coumadin or LMWH or heparinoids (i.e. previous DVT, pulmonary embolism, atrial fibrillation, heart valve replacement)
- Patients with contraindications to anticoagulation (coagulopathy e.g, INR>/=1.5, generalized bleeding disorders, peptic ulcer disease, hemorrhagic or ischemic stroke, etc within last 3 months)
- Patients who are unable to undergo a doppler ultrasound of the lower extremities
- Renal insufficiency (creatinine clearance < 30 mL/min)
- Patients who have a body weight < 50 kg
- Patients receiving continuous (indwelling) epidural
- Physician diagnosed acute or chronic hepatic failure
- Pregnancy
- Patients with life expectancy < 6 months
- Platelet count below 100,000/ mm-3
- History of documented VTE within last 3 months.
- Acute bacterial endocarditis
- Cerebral metastasis or abscess
- Inability to consent
- Refusal by treating physician
About this study
This trial is a prospective, single-center Phase II randomized study to demonstrate the superior efficacy of Fondaparinux Sodium subcutaneous injections in patients undergoing CABG surgery (isolated and redo isolated) versus treatment with placebo. All consecutive patients scheduled for CABG surgery that meet the general inclusion and none of the exclusion criteria will be considered for enrollment in the study.
Consecutive patients will be randomized on the day of admission prior to their CABG surgery into one of two groups. One group will be randomized to the placebo while the second group will receive 2.5 mg Fondaparinux Sodium injections. Both groups will receive routine mechanical prophylaxis as determined by the treating physicians. Group randomized to receive Fondaparinux Sodium will receive a 2.5 mg SQ daily drug dose starting 12 +/- 2 hours post-wound closure or the following day in the morning (at the discretion of the cardiothoracic surgeon). The second dose would be administered 24 hours later and the dosing will then be once a day. The group randomized to placebo will receive subcutaneous equivolume isotonic saline at the same time points described above.
Read more
Patients randomized will receive a 2.5 mg dose of Fondaparinux Sodium or placebo subcutaneously for a total of 3-9 days post CABG with day 1 being the day of surgery. The drug will be discontinued if the patient is discharged before day 9. If the patient stays for more than 9 days inside hospital, a duplex would be obtained per protocol and further DVT prevention measures would be instituted per the discretion of treating physician.
Patients will be assessed daily while hospitalized for any symptoms and adverse reactions and will undergo laboratory testing (CBC, PT/INR, PTT and UA) as specified in the protocol. Post-op day 3-9(no later than 2 days after the last preventive drug dose) patients will undergo the protocol specific lower limb venous duplex scan and earlier if symptomatic. Patients will also be contacted (phone/office visit) for follow-up 25-35 days post CABG to assess for signs or symptoms of deep venous thrombosis or thromboembolism and for any potential complications.
Read the detailed description
Background Information
Venous thromboembolism (VTE) following coronary artery bypass graft (CABG) surgery is a formidable risk in view of various predisposing factors including restriction of activity, history of myocardial infarctions in such patients, presence of multiple predisposing baseline demographic characteristics and risk factors including advanced age and smoking. The reported incidence of asymptomatic deep vein thrombosis (DVT) using duplex ultrasound (DUS) is significant and varies from 16 to 48%, most of the thrombi being calf vein. (1,2,3) The incidence of symptomatic VTE based chiefly on retrospective data ranges from 0.5 to 3.9% for VTE, 0.3 to 0.5% for DVT, 0.2 to 3.9% for PE, and 0.06 to 0.7% for fatal PE. (2-10)The absolute number of affected patients may be significant since the number of such procedures performed every year in the US alone is huge. According to the American Heart Association's Heart Disease and Stroke Statistics - 2008 Update, 469,000 surgical revascularizations were done in the US in 2005.
The benefits of thromboprophylaxis in medically ill patients including those with congestive heart failure have been well demonstrated with up to 60% reduction in VTE risk. (11) The patients who undergo CABG have similar risk profiles and hence should be evaluated with pharmacokinetic thromboprophylacic strategy.
In CABG patients, the American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition), 2008, (12) does recommend routine prophylaxis with low molecular weight heparin (LMWH), low dose unfractionated heparin (LDUH), or optimally used bilateral graduated compression stockings (GCS) or intermittent pneumatic compression (IPC). The guidelines are based on moderate to low quality evidence and the strength of these recommendations is weak as there have been no randomized controlled trials.
Rationale In CABG patients, the American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition), 2008,(12) recommend routine prophylaxis with LMWH, LDUH, or optimally used bilateral GCS or IPC. The guidelines are based on moderate to low quality evidence and the strength of the recommendation is weak as there have been no randomized controlled trials. Optimally used stockings may not be applicable to many CABG patients because of saphenous vein harvesting and hence pharmacologic means are preferable.
Fondaparinux is a pentasaccharide with an efficacy and safeties shown to be equal to or better than LMWH and thus may be a preferred agent for VTE prophylaxis. (13-18)
OBJECTIVES The primary goal of this study is to demonstrate the superiority of Fondaparinux Sodium over placebo for the prevention of VTE in Patients undergoing Coronary Bypass Graft Surgery (CABG).
Primary Efficacy Endpoint:
- Cumulative incidence of all VTE (defined as symptomatic and asymptomatic deep-vein thrombosis, fatal and non-fatal pulmonary embolism, or both) up to day 11
Secondary Efficacy Endpoints:
- Primary efficacy end-point and VTE up to day 35
Primary Safety Endpoints:
- Major bleeding event up to day 11
Secondary Safety Endpoints:
- Cumulative major and minor bleeding event up to day 11
- Deaths, requirement of transfusions and other adverse events up to day 35
STUDY DESIGN This trial is a phase II, prospective, single-center, assessor and patient-blinded, placebo controlled, randomized study to demonstrate the superior thromboprophylactic efficacy of Fondaparinux Sodium subcutaneous injections in patients undergoing CABG surgery versus placebo.
OBJECTIVES The primary efficacy objectives include an assessment of the cumulative rate of all VTE (defined as DVT or fatal or non-fatal pulmonary embolism or both) up to 11 days post CABG. The primary safety objectives include the assessment of the frequency and occurrence of all major bleeding events post-operatively up to day 3-11. Finally, the secondary efficacy objective will include cumulative VTE events and assessment of the components of VTE while the secondary safety objective will include an assessment of the frequency of non-major bleeding events up to day 3-11 as well as all cause deaths, need for transfusion and other monitored adverse events till day 35. The inclusion of safety is mainly for descriptive purposes because the study is not be powered for safety end points.
The safety and efficacy endpoints will determine Fondaparinux Sodium's ability over placebo to prevent VTE while assessing the bleeding risk in this study population. A randomized control is needed because a head to head comparison of Fondaparinux Sodium and placebo is being planned.
Approximate time to complete study enrollment is 2 years. This estimation is based on the number of subjects needed for the study and the rate of CABG surgery performed at the institution.
- Being tested
- Fondaparinux, Placebo
- Keywords
- deep vein thrombosis, coronary artery bypass surgery, Venous thromboembolism
- Medical subject headings
- Venous Thrombosis, Venous Thromboembolism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FondaparinuxDrug
Also called DVT, CABG
Patients will receive a 2.5 mg dose of Fondaparinux subcutaneously for a total of 7 days post CABG
PlaceboOther
Also called DVT, CABG
subcutaneous equivolume isotonic saline
| Study group | Role | What they receive |
|---|---|---|
| Fondaparinux | Active comparator | Patients will receive a 2.5 mg dose of Fondaparinux subcutaneously for a total of 7 days post CABG Receives: Drug: Fondaparinux |
| Placebo | Placebo comparator | Not described Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Venous Thromboembolisms and/or Major Hemorrhages to Day 11
there were 2 events; one in placebo group and one in fondaparinux group
Measured: 11 days
Secondary outcomes (1)
Number of Participants With a Venous Thromboembolisms to 35 Days
Measured: 35 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Nov 2008 (estimated)
- Study start19 Nov 2009
- Primary completion21 Sep 2013
- Study completion21 Sep 2013
Why it stopped: Principal Investigator moved to another region of the country
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Deep Vein 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 78 participants (actual)
Sponsor and investigators
- Lead sponsor
- Prairie Education and Research Cooperative
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- American College of Phlebology
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00789399
- Sponsor's protocol ID
- 00508826
- Status last verified
- Aug 2022
- First submitted
- 7 Nov 2008
- Last updated
- 8 Sep 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Kolluri R, Plessa AL, Sanders MC, Singh NK, Lucore C. A randomized study of the safety and efficacy of fondaparinux versus placebo in the prevention of venous thromboembolism after coronary artery bypass graft surgery. Am Heart J. 2016 Jan;171(1):1-6. doi: 10.1016/j.ahj.2015.10.013. Epub 2015 Oct 21.
PubMed 26699594
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study of the Efficacy of Preventive Dosing of Fondaparinux Sodium Versus Placebo for the Prevention of Venous Thromboembolism (VTE) in Patients Undergoing Coronary Bypass Surgery Receiving Routine Mechanical Prophylaxis
- ClinicalTrials.gov ID
- NCT00789399
- Acronym / sponsor ID
- 00508826
- Keywords
- deep vein thrombosis, coronary artery bypass surgery, Venous thromboembolism
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Principal Investigator moved to another region of the country
- Enrolment
- 78 participants (actual)
- Lead sponsor
- Prairie Education and Research CooperativeIndustry (pharma, biotech, devices)
- Collaborators
- American College of Phlebology
- Study start
- 19 Nov 2009 (actual)
- Primary completion
- 21 Sep 2013 (actual)
- Study completion
- 21 Sep 2013 (actual)
- First posted
- 11 Nov 2008 (estimated)
- Results
- Posted 8 Sep 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This trial is a prospective, single-center Phase II randomized study to demonstrate the superior efficacy of Fondaparinux Sodium subcutaneous injections in patients undergoing CABG surgery (isolated and redo isolated) versus treatment with placebo. All consecutive patients scheduled for CABG surgery that meet the general inclusion and none of the exclusion criteria will be considered for enrollment in the study.
Consecutive patients will be randomized on the day of admission prior to their CABG surgery into one of two groups. One group will be randomized to the placebo while the second group will receive 2.5 mg Fondaparinux Sodium injections. Both groups will receive routine mechanical prophylaxis as determined by the treating physicians. Group randomized to receive Fondaparinux Sodium will receive a 2.5 mg SQ daily drug dose starting 12 +/- 2 hours post-wound closure or the following day in the morning (at the discretion of the cardiothoracic surgeon). The second dose would be administered 24 hours later and the dosing will then be once a day. The group randomized to placebo will receive subcutaneous equivolume isotonic saline at the same time points described above.
Patients randomized will receive a 2.5 mg dose of Fondaparinux Sodium or placebo subcutaneously for a total of 3-9 days post CABG with day 1 being the day of surgery. The drug will be discontinued if the patient is discharged before day 9. If the patient stays for more than 9 days inside hospital, a duplex would be obtained per protocol and further DVT prevention measures would be instituted per the discretion of treating physician.
Patients will be assessed daily while hospitalized for any symptoms and adverse reactions and will undergo laboratory testing (CBC, PT/INR, PTT and UA) as specified in the protocol. Post-op day 3-9(no later than 2 days after the last preventive drug dose) patients will undergo the protocol specific lower limb venous duplex scan and earlier if symptomatic. Patients will also be contacted (phone/office visit) for follow-up 25-35 days post CABG to assess for signs or symptoms of deep venous thrombosis or thromboembolism and for any potential complications.
Detailed description
Background Information
Venous thromboembolism (VTE) following coronary artery bypass graft (CABG) surgery is a formidable risk in view of various predisposing factors including restriction of activity, history of myocardial infarctions in such patients, presence of multiple predisposing baseline demographic characteristics and risk factors including advanced age and smoking. The reported incidence of asymptomatic deep vein thrombosis (DVT) using duplex ultrasound (DUS) is significant and varies from 16 to 48%, most of the thrombi being calf vein. (1,2,3) The incidence of symptomatic VTE based chiefly on retrospective data ranges from 0.5 to 3.9% for VTE, 0.3 to 0.5% for DVT, 0.2 to 3.9% for PE, and 0.06 to 0.7% for fatal PE. (2-10)The absolute number of affected patients may be significant since the number of such procedures performed every year in the US alone is huge. According to the American Heart Association's Heart Disease and Stroke Statistics - 2008 Update, 469,000 surgical revascularizations were done in the US in 2005.
The benefits of thromboprophylaxis in medically ill patients including those with congestive heart failure have been well demonstrated with up to 60% reduction in VTE risk. (11) The patients who undergo CABG have similar risk profiles and hence should be evaluated with pharmacokinetic thromboprophylacic strategy.
In CABG patients, the American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition), 2008, (12) does recommend routine prophylaxis with low molecular weight heparin (LMWH), low dose unfractionated heparin (LDUH), or optimally used bilateral graduated compression stockings (GCS) or intermittent pneumatic compression (IPC). The guidelines are based on moderate to low quality evidence and the strength of these recommendations is weak as there have been no randomized controlled trials.
Rationale In CABG patients, the American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition), 2008,(12) recommend routine prophylaxis with LMWH, LDUH, or optimally used bilateral GCS or IPC. The guidelines are based on moderate to low quality evidence and the strength of the recommendation is weak as there have been no randomized controlled trials. Optimally used stockings may not be applicable to many CABG patients because of saphenous vein harvesting and hence pharmacologic means are preferable.
Fondaparinux is a pentasaccharide with an efficacy and safeties shown to be equal to or better than LMWH and thus may be a preferred agent for VTE prophylaxis. (13-18)
OBJECTIVES The primary goal of this study is to demonstrate the superiority of Fondaparinux Sodium over placebo for the prevention of VTE in Patients undergoing Coronary Bypass Graft Surgery (CABG).
Primary Efficacy Endpoint:
- Cumulative incidence of all VTE (defined as symptomatic and asymptomatic deep-vein thrombosis, fatal and non-fatal pulmonary embolism, or both) up to day 11
Secondary Efficacy Endpoints:
- Primary efficacy end-point and VTE up to day 35
Primary Safety Endpoints:
- Major bleeding event up to day 11
Secondary Safety Endpoints:
- Cumulative major and minor bleeding event up to day 11
- Deaths, requirement of transfusions and other adverse events up to day 35
STUDY DESIGN This trial is a phase II, prospective, single-center, assessor and patient-blinded, placebo controlled, randomized study to demonstrate the superior thromboprophylactic efficacy of Fondaparinux Sodium subcutaneous injections in patients undergoing CABG surgery versus placebo.
OBJECTIVES The primary efficacy objectives include an assessment of the cumulative rate of all VTE (defined as DVT or fatal or non-fatal pulmonary embolism or both) up to 11 days post CABG. The primary safety objectives include the assessment of the frequency and occurrence of all major bleeding events post-operatively up to day 3-11. Finally, the secondary efficacy objective will include cumulative VTE events and assessment of the components of VTE while the secondary safety objective will include an assessment of the frequency of non-major bleeding events up to day 3-11 as well as all cause deaths, need for transfusion and other monitored adverse events till day 35. The inclusion of safety is mainly for descriptive purposes because the study is not be powered for safety end points.
The safety and efficacy endpoints will determine Fondaparinux Sodium's ability over placebo to prevent VTE while assessing the bleeding risk in this study population. A randomized control is needed because a head to head comparison of Fondaparinux Sodium and placebo is being planned.
Approximate time to complete study enrollment is 2 years. This estimation is based on the number of subjects needed for the study and the rate of CABG surgery performed at the institution.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fondaparinux | Active comparator | Drug: FondaparinuxPatients will receive a 2.5 mg dose of Fondaparinux subcutaneously for a total of 7 days post CABG |
| Placebo | Placebo comparator | Other: Placebo |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| FondaparinuxAlso: DVT, CABGPatients will receive a 2.5 mg dose of Fondaparinux subcutaneously for a total of 7 days post CABG | Drug | Fondaparinux |
| PlaceboAlso: DVT, CABGsubcutaneous equivolume isotonic saline | Other | Placebo |
Primary outcome
Number of Participants With Venous Thromboembolisms and/or Major Hemorrhages to Day 11
Time frame: 11 days
there were 2 events; one in placebo group and one in fondaparinux group
1 secondary outcome
Number of Participants With a Venous Thromboembolisms to 35 Days
Time frame: 35 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Sep 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26699594Kolluri R, Plessa AL, Sanders MC, Singh NK, Lucore C. A randomized study of the safety and efficacy of fondaparinux versus placebo in the prevention of venous thromboembolism after coronary artery bypass graft surgery. Am Heart J. 2016 Jan;171(1):1-6. doi: 10.1016/j.ahj.2015.10.013. Epub 2015 Oct 21.
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A study testing Fondaparinux in people with Deep Vein Thrombosis and Coronary Artery Bypass Surgery, run by Prairie Education and Research Cooperative.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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: stopped early, as of the sponsor's last update on 8 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Sep 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Venous Thromboembolisms and/or Major Hemorrhages to Day 11 (time frame: 11 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00789399, which also lists 1 linked publication.
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 8 Sep 2022.