Low-Dose rtPA to Treat Blood Clots in Major Arm or Neck Veins
| Status: | Completed |
|---|---|
| Conditions: | Cardiology |
| Therapuetic Areas: | Cardiology / Vascular Diseases |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/21/2016 |
| Start Date: | February 2003 |
| End Date: | December 2007 |
Treatment of Jugular, Subclavian, and/or Innominate Vein Thrombosis With Low Dose Recombinant Tissue Plasminogen Activator Plus Anticoagulation
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.
(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.
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.
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.
- INCLUSION CRITERIA:
Adults (18 years or older) are eligible for this study.
Patients must be enrolled in or actively being evaluated for a protocol at the Clinical
Center.
Patient must be able to give informed consent and be able to follow anticoagulation
regimen if enrolled.
Occlusive thrombosis of jugular, axillary, subclavian, or brachiocephalic veins must be
documented by ultrasound, or venography (Occlusive meaning complete blockage of blood flow
across affected venous segment). Although most thrombi will be associated with a VAD, this
is not a requirement.
Estimated duration of thrombosis should not exceed 4 weeks based on clinical history.
Postpartum mothers are eligible for this treatment, but nursing mothers will be instructed
to refrain from breast feeding their infants for 24 hours after each venogram or contrast
study.
EXCLUSION CRITERIA:
Pregnancy: Although the abdomen can be shielded from medical radiation required for the
procedures, the use of contrast media, thrombolytic enzymes, and anticoagulation can
potentially have adverse effects on a pregnancy, so that thrombolytic therapy is
contraindicated during pregnancy.
Children are excluded from this protocol but are eligible for the high dose regimen that
is the current standard at NIH.
Patients who are cognitively impaired and cannot give consent will not be eligible for
this protocol. The current high dose regimen remains an option, if appropriate consent can
be obtained from legally responsible guardian or family member.
Patients with known diabetic or other retinopathy will be excluded unless cleared for
treatment by an ophthalmologist.
Gastrointestinal or internal bleeding (except microscopic hematuria) within the previous
two weeks; active peptic ulcer disease; familial or acquired bleeding diathesis not
attributable to heparin administration (prothrombin time greater than 14 s, APTT greater
than 35s, fibrinogen less than 150mg/dl); thrombocytopenia less than 50,000 microliters.
History of cerebrovascular accident or neurosurgery within previous 2 months
Lumbar puncture within previous 2 weeks, or patients with epidural catheters, current or
in the past 2 weeks.
Major surgery, trauma, or deep organ biopsy within the previous 10 days: recent onset
(less than 10 days) of atrial fibrillation without anticoagulation, Known right to left
cardiac shunts, and pulmonary arteriovenous malformations.
Severe hypertension (systolic pressure greater than 200 mmHg, diastolic pressure 110 mmHg)
Renal insufficiency with serum creatinine greater than 2.5mg/dl
History of anaphylactic reaction to iodinated contrast material.
History of heparin-induced thrombocytopenia.
Acute Pericarditis
Known defect of cardiac septum with right to left intracardiac shunt.
Pulmonary arteriovenous malformation.
Bacterial endocarditis.
Intracranial neoplasm, arteriovenous malformation, and aneurysm with evidence, clinically
or by imaging, of hemorrhage in previous 2 months excludes participation. If there has
been no evidence of bleeding, these patients can be considered for participation.
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
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