Low-Dose rtPA to Treat Blood Clots in Major Arm or Neck Veins

Phase 1

Completed

• Conditions: Thrombosis

• Registration Number: NCT00055159
• Lead Sponsor: National Institutes of Health Clinical Center (CC)

Brief Summary

This study will test the effectiveness of low-dose recombinant tissue plasminogen activator (rtPA, or alteplase) in dissolving blood clots in major arm or neck veins. rtPA is given to patients with heart attacks to dissolve blood clots in blocked coronary arteries. Blood clots that develop in major arm or neck veins usually develop after a venous access device (VAD) or catheter has been placed in the vein. The clot often causes arm, shoulder or neck swelling and pressure or discomfort. Current treatments include removing the VAD, using blood thinners such as heparin and warfarin, or using rtPA to dissolve the clot. All these options have disadvantages, however, including the risk of abnormal bleeding. This study will evaluate whether lower doses of rtPA can effectively dissolve clots without requiring an extended hospital stay, as is needed with the current higher-dose regimen.

Patients 18 years of age and older who are enrolled in or are being evaluated for a Clinical Center study and who have a blocked jugular, axillary, subclavian, or brachiocephalic vein may be eligible for this study. The blockage may or may not be associated with use of a VAD.

Participants will have one or two treatments with a low dose of rtPA, followed by a blood thinner taken by mouth or by injection for 5 to 7 weeks. On the first treatment day, the patient has a venogram, in which a catheter is placed in an arm vein and passed up to and through the blood clot that is blocking the blood flow in the vein. This is done under an x-ray machine so the radiologist can see exactly where the tube is going. Then, rtPA is injected into the clot about every 30 seconds for 15 to 30 minutes. The catheter is kept in place to maintain access to the vein for additional treatment the next day, if needed. The patient then begins treatment with heparin, either as an outpatient or an inpatient. A second venogram is done the next day. If the venogram shows that the vein is open, anti-clotting treatment with heparin or warfarin continues. If the venogram shows that the vein is still blocked, the rtPA treatment is repeated while the blood thinner treatment continues. The patient has a third venogram the following day. If the vein has opened, heparin and warfarin treatment continues. If the vein is still blocked, the patient's participation in the study ends. Although the patient is no longer formally in the study, he or she may choose to receive additional treatments with rtPA in higher doses at NIH or to continue using blood thinners under the direction of the primary physician.

Blood tests are done during blood thinning therapy to monitor and adjust the dosage. Additional blood samples are taken before and at timed intervals after each rtPA treatment to measure the response to therapy. Patients who benefit from rtPA treatment remain on blood thinners for 5 to 7 weeks and then return to NIH for a follow-up venogram to see if the vein is still open. During warfarin therapy, blood tests are done every few days during the first week or two and every 2 weeks thereafter to ensure the optimal drug dose is being administered. If the repeat venogram at 5 to 7 weeks shows that the vein has closed, the blood thinners (warfarin or heparin) will be stopped and the patient's participation in this study will end. If the vein has remained open, the patient's doctor will decide whether or not to continue anti-clotting therapy.

Detailed Description

Deep vein thrombosis of the central veins of the upper extremity and neck is most commonly seen at the Clinical Center as a consequence of use of central venous access devices (VADs) required for intravenous medication treatment programs at the NIH. In order to relieve discomfort associated with this condition or restore patency of the central veins, we successfully developed a treatment program employing intraclot pulse-sprayed injection of recombinant tissue plasminogen activator (rtPA) and anticoagulation with heparin plus warfarin (Protocol 95-CC-0053). Recent laboratory kinetic studies of thrombolysis with rtPA suggest that more rapid thrombolysis can be achieved with rtPA doses that are more than 10 times lower than the doses used in our earlier protocol. The purpose of this protocol is to evaluate whether these lower doses translate into more effective thrombolysis in the clinical setting, so that we may modify our thrombolysis treatment to make it more effective, potentially safer, and less costly than our previous protocol. This proposed protocol still utilizes pulse spray injection of rtPA directly into the thrombus as before, but evaluates the efficacy and safety of using a total of 4 mg or less of rtPA each day for thrombolytic therapy. As this lower dose of rtPA has been found to be safe in catheter clearance applications, hospitalization will not be required as part of the protocol. Patients who elect to have this procedure performed as outpatients will also receive anticoagulation with standard regimens using subcutaneous low molecular weight heparin (LMWH) alone, or with gradual conversion to oral warfarin.

Study Timeline

• Study Start: 2003-02-19
• Study First Submitted QC: 2003-02-19
• Study First Submitted: 2003-02-20
• Study First Posted: 2003-02-20
• Status Verified: 2007-12-10
• Study Completion: 2007-12-10
• Last Update Submitted: 2017-06-30
• Last Update Posted: 2017-07-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: Not specified

Trial Locations

Locations (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike; 🇺🇸 Bethesda, Maryland, United States