NIH Clinical Research Studies

Protocol Number: 04-CC-0178

Active Accrual, Protocols Recruiting New Patients

Title:
The Treatment of Deep Vein Thrombosis of the Lower Extremities with "Low-Dose" Alteplase: a Pilot Study
Number:
04-CC-0178
Summary:
This study will test the effectiveness of low-dose recombinant tissue plasminogen activator (rtPA, or alteplase) in dissolving blood clots in deep leg veins. rtPA is given to patients with heart attacks to dissolve blood clots in blocked coronary arteries. Blood clots that develop in the deep leg veins can cause pain and swelling and may break loose and lodge in the lungs. Current Routine treatments use anticoagulants (blood thinners) such as heparin, or rtPA to dissolve the clots to stop the clots from enlarging. In an earlier study we showed that rtPA could be used to actually dissolve the clots. This study will determine whether lower doses of rtPA can effectively dissolve clots with fewer bleeding complications than the current previous higher-dose regimen.

Patients 18 years of age and older who have blood clots in a deep vein of the pelvis or leg may be eligible for this study if they have had symptoms for 14 days or less and if they have never had clots in their deep veins before.

Participants are admitted to hospital for 3 to 5 days. On the first treatment day, the patient has a venogram to show the location of the clots. The radiologist injects an x-ray contrast material into a small vein in the foot and watches the dye by x-ray as it moves up the leg, revealing the clot(s). A catheter (plastic tube) is then inserted into a vein either behind the knee, in the groin, or in the neck, and advanced until it reaches the clots. When the catheter is in place, rtPA is injected while the radiologist watches the vein under the x-ray image. The amount of rtPa needed will depends on the size of the clot. Up to five venograms may be done if the clot requires the maximum four rtPA treatments allowed in this study. During the treatments, patients receive standard doses of heparin, given continuously by vein, and Coumadin, another blood thinner, taken by mouth. Patients continue taking Coumadin for 6 months.

Blood samples are drawn shortly before the first dose of rtPa and at five time points afterward to measure the rtPa in the circulation and other factors that indicate whether the rtPa is affecting clotting ability. Blood also is drawn at least once a day to monitor heparin levels.

To evaluate the impact of treatment on the function of the leg, patients are evaluated in the Rehabilitation Medicine Department before receiving rtPA and again at the end of the hospitalization. Patients are also fitted for a compression stocking for the leg, which should be worn to reduce the chance of swelling.

Sponsoring Institute:
National Institutes of Health Clinical Center (CC)
Recruitment Detail
Type: Participants currently recruited/enrolled
Gender: Male & Female
Referral Letter Required: Yes
Population Exclusion(s): Children

Eligibility Criteria:
INCLUSION CRITERIA

Only adult patients (18 years old or older) are included.

Patients must have thrombosis documented by ultrasound or venography to involve the deep veins of the pelvis and/or a lower extremity proximal to the calf veins, i.e., the popliteal vein or above.

The thrombosis must be the patient's first DVT.

The thrombosis must have been symptomatic for no more than 14 days.

Patients must be able to give informed consent and be able to follow the prescribed anticoagulation regimen.

Patients on concurrent NIH protocols will be eligible as well as patients from the community and the rest of the U.S. who are not already on NIH protocols.

EXCLUSION CRITERIA

Pregnant patients are not eligible, although postpartum mothers over 10 days from delivery are eligible if they refrain from breast feeding their infants for 24 hours after each study with x-ray contrast material.

Serum creatinine greater than than 2 mg/dL.

Any current bleeding diathesis not attributable to heparin or warfarin. Fibrinogen less than 150 mg/dL. Any patient with a prothrombin time greater than 15 s, an aPTT greater than 35 s, or a platelet count less than 100,000/microL must be evaluated by the Hematology Service for a coagulopathy before being included.

Within the previous 10 days: major surgery or trauma, puncture of a noncompresssible vessel, organ biopsy, or cardiopulmonary resusitation.

Within the previous 2 months: cerebrovascular infarction or hemorrhage, or intracranial or intraspinal surgery or trauma.

Within the previous 6 months: major internal bleeding.

Active intracranial disease (aneurysm, vascular malformation, neoplasm).

Life expectancy less than 6 months.

Patients with hemoglobin concentration less than 9g/dL will not participate in the pharmacokinetic portion of the protocol.

Uncontrolled systolic blood pressure greater than 180 mm Hg or diastolic greater than 100 mm Hg.

Atrial fibrillation, unless a cardiac echocardiogram excludes the presence of intracardiac thrombus.

Known right-to-left intracardiac shunt.

Pericarditis, infective endocarditis.

History of heparin-induced thrombocytopenia within 6 months or the presence of persistent anti-heparin antibodies by ELISA.

History of anaphylactic reactions to x-ray contrast media.

Known retinopathy unless cleared by an ophthalmologist at NIH.

Evidence of uncontrolled congestive heart failure or a history of diabetes mellitus.

Special Instructions:
Currently Not Provided
Keywords:
RT PA
Thrombolysis
Clot
Anticoagulation
Fibrirolysis
Recruitment Keyword(s):
Deep Vein Thrombosis
DVT
Condition(s):
Venous Thrombosis
Investigational Drug(s):
Alteplase (Activase, Genentech)
Investigational Device(s):
None
Intervention(s):
Drug: Alteplase (Activase, Genentech)
Supporting Site:
Warren G. Magnuson Clinical Center

Contact(s):
Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citation(s):
Schafer AI. Venous thrombosis as a chronic disease. N Engl J Med. 1999 Mar 25;340(12):955-6. No abstract available.

Prandoni P, Lensing AW, Cogo A, Cuppini S, Villalta S, Carta M, Cattelan AM, Polistena P, Bernardi E, Prins MH. The long-term clinical course of acute deep venous thrombosis. Ann Intern Med. 1996 Jul 1;125(1):1-7.

Levine M, Hirsh J, Weitz J, Cruickshank M, Neemeh J, Turpie AG, Gent M. A randomized trial of a single bolus dosage regimen of recombinant tissue plasminogen activator in patients with acute pulmonary embolism. Chest. 1990 Dec;98(6):1473-9.

Active Accrual, Protocols Recruiting New Patients

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