Saphenous Vein Graft DiseasePhase 1/2NCT00264706
PolyArginine Treated vEiN grafTs (PATENT)
A Phase 1/2 study testing Nona-L-arginine in people with Saphenous Vein Graft Disease, run by Lumen Therapeutics at 1 site in Canada.
Trial summary
The primary objectives of this trial are: 1) to evaluate the safety of NONA-L-ARGININE in ex vivo application to saphenous vein segments prior to grafting; and, 2) to obtain preliminary data on the biological effects of NONA-L-ARGININE, as compared to placebo, in the prevention of neointimal hyperplasia. Read more about this study
- Who is it for?
- Ages 35 to 85 years
- Conditions the study is for
- Saphenous Vein Graft Disease
- What is being tested?
- Nona-L-arginine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteCanada
- Study dates
- Mar 2005to Apr 2008
- Phase
- Phase 1/2
- 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 35 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject must be 35-85 years of age and able to give informed consent.
- Coronary artery disease requiring bypass grafting using at least two saphenous vein bypass grafts carried out through median sternotomy and utilizing cardiopulmonary bypass.
- Use of an approved statin anticipated for at least 24 months after surgery.
- Subject must not be a candidate for concurrent ventricular surgical restoration, AICD placement, or valvular surgery.
- Agreeable to CTA at 6 weeks and IVUS intervention at 12-months post-CABG. Subjects agreeable to additional CTA at 6, 12 and 24 months preferred.
Who cannot join
- Acute traumatic injury or vasculitis.
- Insulin-dependent diabetes.
- Procedure is for revision for an existing bypass graft.
- Procedure is to be minimally invasive (except for harvesting of the graft segment).
- Concurrent cardiac valvular surgery.
- Patients with any medical condition that, in the investigator's judgment, makes the patient ineligible or places the patient at undue risk (e.g. conditions that preclude standard invasive follow-up procedures such as IVUS and angiography, i.e. renal failure, bleeding diathesis, or peripheral vascular disease preventing catheterization via the groin).
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- Subject has clinical evidence of infection that the Investigator deems significant to the completion of the procedure, or that could compromise the subject's safety.
- Subject has recent history (within past 6 months) of alcohol or drug abuse.
- If female, subject is pregnant or trying to become pregnant.
- Calculated creatinine clearance < 30 mls/min for non-diabetics or < 50 mls/min for non-insulin dependent diabetics.
Trial locations and contacts
1 site in 1 country.
About this study
The primary objectives of this trial are: 1) to evaluate the safety of NONA-L-ARGININE in ex vivo application to saphenous vein segments prior to grafting; and, 2) to obtain preliminary data on the biological effects of NONA-L-ARGININE, as compared to placebo, in the prevention of neointimal hyperplasia.
Read the detailed description
LT-1951 is an aqueous solution of NONA-L-ARGININE. The drug efficiently penetrates into vascular tissues like the saphenous vein and supplies the tissue with a sustained reservoir of L-arginine, the substrate for production of nitric oxide. Nitric oxide (NO) is an important vasoactive and cell signaling compound implicated in suppression of neointimal hyperplasia. NO limits neointimal hyperplasia by inhibiting monocyte chemotaxis and adherence, platelet adherence and aggregation, and vascular smooth muscle cell proliferation.
A dramatic reduction of neointimal hyperplasia following treatment with LT-1951 has been demonstrated in preclinical vein to artery interposition studies in several animal models. Marked improvement following a single ex vivo application of LT-1951 in interposition grafts demonstrated that the beneficial effect of the drug is not dependent upon continued treatment of the grafted tissue.
In the PATENT trial, saphenous vein grafts are harvested in the usual manner from the patient's leg and are bathed in LT-1951 or placebo ex vivo (at normal pressure and temperature) before being rinsed and implanted into the patient. Because LT-1951 is applied only to the graft, there is minimal systemic exposure and risk to the patient.
All patients in this study will receive treatment with both NONA-L-ARGININE and vehicle control. This within-patient, placebo-controlled, study will be double-blinded and randomized. For each patient, one of the comparable vein grafts will receive treatment with placebo, while the other will receive treatment with NONA-L-ARGININE. Any third vein graft used in the procedure will be treated as per the first vein graft, while any fourth vein graft will be treated as per the second vein graft.
The first cohort of 20 patients will be the primary safety subgroup. This subgroup will be evaluated in combination with a second cohort of 30-80 patients for assessment of efficacy endpoints. During follow-up, all patients will have clinical visits at 6 weeks, which will include Computed Tomographic Angiography (CTA). Patients will undergo Intravascular Ultrasound-coronary angiography (IVUS-angio) at 12 months and optional CTA at 6, 12 and 24 months.
- Conditions
- Saphenous Vein Graft Disease
- Being tested
- Nona-L-arginine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nona-L-arginineDrug
| Study group | Role | What they receive |
|---|---|---|
| Participant | Other | Internal control study Receives: Drug: Nona-L-arginine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety - as assessed by the nature and frequency of clinical adverse event at 6 weeks post-surgery.
Measured: 6 weeks
Efficacy - Volume obstruction of the vein grafts measured by IVUS at 1 year.
Measured: 1 year
Secondary outcomes (1)
1. Volume obstruction adjacent to the proximal and distal anastomoses, and within the body of the graft; 2. Intima:media ratio; 3. Minimal and maximal luminal diameter; and, 4. lumen volume:vessel volume.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Dec 2005 (estimated)
- Study startMar 2005
- Primary completionApr 2008
- Study completionApr 2008
Why it stopped: Reformulation of test compound
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Saphenous Vein Graft DiseaseStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lumen Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Stephanie Brister, M.D., Principal investigator, Toronto General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00264706
- Sponsor's protocol ID
- Lumen-01-CS-1
- Status last verified
- Sep 2016
- First submitted
- 11 Dec 2005
- Last updated
- 8 Sep 2016
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PolyArginine Treated vEiN grafTs (PATENT)
- ClinicalTrials.gov ID
- NCT00264706
- Acronym / sponsor ID
- Lumen-01-CS-1
- Conditions
- Saphenous Vein Graft Disease
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Reformulation of test compound
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Lumen TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Mar 2005
- Primary completion
- Apr 2008 (actual)
- Study completion
- Apr 2008 (actual)
- First posted
- 13 Dec 2005 (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.
The primary objectives of this trial are: 1) to evaluate the safety of NONA-L-ARGININE in ex vivo application to saphenous vein segments prior to grafting; and, 2) to obtain preliminary data on the biological effects of NONA-L-ARGININE, as compared to placebo, in the prevention of neointimal hyperplasia.
Detailed description
LT-1951 is an aqueous solution of NONA-L-ARGININE. The drug efficiently penetrates into vascular tissues like the saphenous vein and supplies the tissue with a sustained reservoir of L-arginine, the substrate for production of nitric oxide. Nitric oxide (NO) is an important vasoactive and cell signaling compound implicated in suppression of neointimal hyperplasia. NO limits neointimal hyperplasia by inhibiting monocyte chemotaxis and adherence, platelet adherence and aggregation, and vascular smooth muscle cell proliferation.
A dramatic reduction of neointimal hyperplasia following treatment with LT-1951 has been demonstrated in preclinical vein to artery interposition studies in several animal models. Marked improvement following a single ex vivo application of LT-1951 in interposition grafts demonstrated that the beneficial effect of the drug is not dependent upon continued treatment of the grafted tissue.
In the PATENT trial, saphenous vein grafts are harvested in the usual manner from the patient's leg and are bathed in LT-1951 or placebo ex vivo (at normal pressure and temperature) before being rinsed and implanted into the patient. Because LT-1951 is applied only to the graft, there is minimal systemic exposure and risk to the patient.
All patients in this study will receive treatment with both NONA-L-ARGININE and vehicle control. This within-patient, placebo-controlled, study will be double-blinded and randomized. For each patient, one of the comparable vein grafts will receive treatment with placebo, while the other will receive treatment with NONA-L-ARGININE. Any third vein graft used in the procedure will be treated as per the first vein graft, while any fourth vein graft will be treated as per the second vein graft.
The first cohort of 20 patients will be the primary safety subgroup. This subgroup will be evaluated in combination with a second cohort of 30-80 patients for assessment of efficacy endpoints. During follow-up, all patients will have clinical visits at 6 weeks, which will include Computed Tomographic Angiography (CTA). Patients will undergo Intravascular Ultrasound-coronary angiography (IVUS-angio) at 12 months and optional CTA at 6, 12 and 24 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Participant | Other | Drug: Nona-L-arginineInternal control study |
Who may qualify
- Ages
- 35 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Subject must be 35-85 years of age and able to give informed consent.
- Coronary artery disease requiring bypass grafting using at least two saphenous vein bypass grafts carried out through median sternotomy and utilizing cardiopulmonary bypass.
- Use of an approved statin anticipated for at least 24 months after surgery.
- Subject must not be a candidate for concurrent ventricular surgical restoration, AICD placement, or valvular surgery.
- Agreeable to CTA at 6 weeks and IVUS intervention at 12-months post-CABG. Subjects agreeable to additional CTA at 6, 12 and 24 months preferred.
Key exclusion criteria (10 listed)
- Acute traumatic injury or vasculitis.
- Insulin-dependent diabetes.
- Procedure is for revision for an existing bypass graft.
- Procedure is to be minimally invasive (except for harvesting of the graft segment).
- Concurrent cardiac valvular surgery.
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 |
|---|---|---|
| Nona-L-arginine | Drug | Participant |
Primary outcome
Safety - as assessed by the nature and frequency of clinical adverse event at 6 weeks post-surgery.
Time frame: 6 weeks
Efficacy - Volume obstruction of the vein grafts measured by IVUS at 1 year.
Time frame: 1 year
1 secondary outcome
1. Volume obstruction adjacent to the proximal and distal anastomoses, and within the body of the graft; 2. Intima:media ratio; 3. Minimal and maximal luminal diameter; and, 4. lumen volume:vessel volume.
Time frame: 1 year
Results and safety
The study was stopped early (reason given: Reformulation of test compound). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Sep 2016.
- Click here for additional information on Saphenous Vein Graft Disease and the PATENT study.Link provided by the sponsor.
Related trials for Saphenous Vein Graft Disease
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Photobiomodulation in Coronary Artery Bypass Grafting With No-Touch vs Conventional Saphenous Vein Harvesting.
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Recruiting
Saphenous Vein as Y-composite Versus Aortocoronary Conduit for CABG
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Ticagrelor-Based Dual Antiplatelet Therapy Duration in CABG
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Recruiting
Shockwave Intervention for Enhanced Wound Healing in No-touch Pedicle Saphenous Vein Graft Harvesting for Coronary Artery Bypass Grafting
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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.
Stephanie Brister, M.D. principal investigator
Toronto General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Nona-L-arginine in people with Saphenous Vein Graft Disease, run by Lumen Therapeutics at 1 site in Canada.
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 5 inclusion and 10 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: stopped early, as of the sponsor's last update on 8 Sep 2016. 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 Canada. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 was stopped early (reason given: Reformulation of test compound). Results are not available in the source record.
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?
Safety - as assessed by the nature and frequency of clinical adverse event at 6 weeks post-surgery. (time frame: 6 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2016.