ThrombosisPhase 1NCT00055159
Low-Dose rtPA to Treat Blood Clots in Major Arm or Neck Veins
A Phase 1 study testing Pulse-sprayed injection of recombinant tissue plasminogen activator (rtPA) in people with Thrombosis, run by National Institutes of Health Clinical Center (CC) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Thrombosis
- What is being tested?
- Pulse-sprayed injection of recombinant tissue plasminogen activator (rtPA)
- Type of treatment
- Injection or infusion, Surgery or procedure
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Feb 2003to 10 Dec 2007
- Phase
- Phase 1
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 17Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: 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.
Read more
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.
Read the 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.
- Conditions
- Thrombosis
- Being tested
- Pulse-sprayed injection of recombinant tissue plasminogen activator (rtPA)
- Keywords
- RT PA, Blood Clots, Catheter Directed Thrombolytic Therapy, Alteplase, Deep Vein Thrombosis, DVT
- Medical subject headings
- Thrombosis, Venous Thrombosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pulse-sprayed injection of recombinant tissue plasminogen activator (rtPA)Procedure or surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2003 (estimated)
- Study start19 Feb 2003
- Study completion10 Dec 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for 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 1
- Primary purpose
- Treatment
- Enrolment
- 50 participants
Sponsor and investigators
- Lead sponsor
- National Institutes of Health Clinical Center (CC)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00055159
- Sponsor's protocol ID
- 030113
- Other IDs
- 03-CC-0113
- Status last verified
- 10 Dec 2007
- First submitted
- 20 Feb 2003
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Turpie AG, Levine MN, Hirsh J, Ginsberg JS, Cruickshank M, Jay R, Gent M. Tissue plasminogen activator (rt-PA) vs heparin in deep vein thrombosis. Results of a randomized trial. Chest. 1990 Apr;97(4 Suppl):172S-175S.
PubMed 2108855
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Jugular, Subclavian, and/or Innominate Vein Thrombosis With Low Dose Recombinant Tissue Plasminogen Activator Plus Anticoagulation
- ClinicalTrials.gov ID
- NCT00055159
- Acronym / sponsor ID
- 030113
- Conditions
- Thrombosis
- Keywords
- RT PA, Blood Clots, Catheter Directed Thrombolytic Therapy, Alteplase, Deep Vein Thrombosis, DVT
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants
- Lead sponsor
- National Institutes of Health Clinical Center (CC)US National Institutes of Health
- Study start
- 19 Feb 2003
- Study completion
- 10 Dec 2007
- First posted
- 20 Feb 2003 (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.
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 design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (17 listed)
- 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.
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 |
|---|---|---|
| Pulse-sprayed injection of recombinant tissue plasminogen activator (rtPA) | Procedure or surgery | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Background: PubMed 2108855Turpie AG, Levine MN, Hirsh J, Ginsberg JS, Cruickshank M, Jay R, Gent M. Tissue plasminogen activator (rt-PA) vs heparin in deep vein thrombosis. Results of a randomized trial. Chest. 1990 Apr;97(4 Suppl):172S-175S.
Related trials for Thrombosis
Not yet recruitingPhase 3
TicAgreLor Versus Placebo to Prevent Cerebral ISCHemia in anEuRysmal Low Grade SAH A Double Blinded Randomised Controlled Study
Subarachnoid Hemorrhage, Aneurysmal, Brain Ischemia
RecruitingObservational study
Study of the Long-Term Safety and Outcomes of Treating Pulmonary Embolism With the Indigo Aspiration System
Pulmonary Embolism
RecruitingPhase 2
SBRT With Immunotherapy and Atezo-Bev in HCC With Major Portal Vein Thrombosis
HCC
Not yet recruiting
Pilot Study Evaluating Catheter Directed Thrombolysis Device in Acute Intermediate Risk Pulmonary Embolism
Pulmonary Embolism (PE), Pulmonary Embolism With Right Ventricle Enlargement
Active, not recruitingObservational study
Real World Evidence in China: Faricimab Use in Diabetic Macular Edema, Retinal Vein Occlusion, and Neovascular Age-Related Macular Degeneration (The Farseeing Study)
Diabetic Macular Edema, Neovascular Age-related Macular Degeneration
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Pulse-sprayed injection of recombinant tissue plasminogen activator (rtPA) in people with Thrombosis, run by National Institutes of Health Clinical Center (CC) at 1 site in United States.
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 6 inclusion and 17 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: finished, as of the sponsor's last update on 2 Jul 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 United States. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00055159, 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 2 Jul 2017.