Investigation by the Thoraxcenter on Antisense DNA Using Local Delivery and IVUS After Coronary Stenting - ITALICS

Jan 30, 2002
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Date Published:
01/01/1998
Date Updated:
01/30/2002
Original Posted Date:
01/30/2002
References

Description:

LR-3280 antisense DNA on restenosis after stent implantation.

Hypothesis:

To evaluate the efficacy of LR-3280 (antisense oligodeoxyribonucleotide directed against c-myc) on restenosis after stent implantation.

Study Design

Study Design:

Patients Screened: Not given
Patients Enrolled: 84

Patient Populations:

At least 21 years of age
Single de novo or restenotic coronary lesion suitable for intracoronary stent implantation
Target lesion greater than 50% stenosis
Informed consent

Exclusions:

Angina pectoris within 48 hours
MI within 15 days
LVEF less than 35%
Renal impairment
Hepatic dysfunction
Vein graft occlusion
Ostial lesions
Total occlusions

Primary Endpoints:

Percent instent volume obstruction as measured by IVUS at 6-month follow-up catheterization.

Secondary Endpoints:

Mean and minimal lumen diameter, loss index, and late loss of the stented segment by QCA at 6 months
Composite outcome (and each component of) cardiac death, myocardial infarction, and revascularization of the treated vessel within 12 months
Feasibility, safety, and tolerability of the administration of LR-3280 within a stented segment using a local delivery device.

Drug/Procedures Used:

LR-3280, delivered locally in divided doses of 10mg each for 1, 2, or 3 deliveries, depending on the length of the stented segment; vs. placebo.

Principal Findings:

There were no differences in percent neointimal volume obstruction, restenosis rate, loss index, or clinical outcome between placebo (saline vehicle) and administration of 10 mg. of antisense compound LR-3280.

Interpretation:

The investigators listed the following as potential reasons for the study results: (1) Because of the broad inclusion criteria, there was a general inhomogeneity of lesions (long, complex, calcified). (2) The saline vehicle may mask any beneficial effect. (3) The use of the self-expanding stainless steel stent and the resulting chronic wall stress may interfere with the action of LR-3280. (4) The dose of LR-3280 may have been insufficient. (5) Intraluminal delivery may not be efficient enough. (6) "Single-shot" therapy may not be effective, considering the time course of c-myc expression. (7) LR-3280 may not be effective. Overall, significant technical and developmental challenges remain for gene-based therapy.

References:

1. Presented at the XXth Congress of the European Society of Cardiology, Vienna, 1998

Keywords: Oligonucleotides, Genetic Therapy, Stainless Steel, Coronary Restenosis, Research Personnel, Constriction, Pathologic, Informed Consent, Stents


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