PolyArginine Treated vEiN grafTs (PATENT)
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||PolyArginine Treated vEiN grafTs (PATENT)|
- Safety - as assessed by the nature and frequency of clinical adverse event at 6 weeks post-surgery. [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
- Efficacy - Volume obstruction of the vein grafts measured by IVUS at 1 year. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
|Study Start Date:||March 2005|
|Study Completion Date:||April 2008|
|Primary Completion Date:||April 2008 (Final data collection date for primary outcome measure)|
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00264706
|Toronto General Hospital|
|Toronto, Ontario, Canada, M5G 2C4|
|Principal Investigator:||Stephanie Brister, M.D.||Toronto General Hospital|