Therapeutic Angiogenesis With Intramuscular NV1FGF in Patients With Critical Limb Ischemia - TALISMAN

Mar 12, 2006
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Date Presented:
01/01/2006
Date Published:
01/01/2008
Date Updated:
03/12/2006
Original Posted Date:
03/12/2006
References

Description:

The goal of the trial was to evaluate treatment with intramuscular NV1FGF, a pCOR plasmid for expression of fibroblast growth factor-1 (FGF-1) compared with placebo among patients with critical limb ischemia (CLI).

Study Design

Patients Enrolled: 107
Mean Follow Up: One year
Mean Patient Age: Mean age 72 years
Female: 41

Patient Populations:

Critical limb ischemia with non-healing ulcers and no option for revascularization

Primary Endpoints:

Incidence of complete healing of ≥1 ulcer at week 25

Secondary Endpoints:

Amputation, death, ankle brachial index (ABI), and transcutaneous oxygen pressure (TcPO2)

Drug/Procedures Used:

Patients were randomized to 8 intramuscular injections of 2.5 ml NV1FGF at 0.2 mg/ml (n=59) or placebo (n=66) on days 1, 15, 30, and 45.

Principal Findings:

Diabetes was present in 26% of patients and coronary artery disease in 22%. Ankle brachial index was 0.4 in each group. There was no difference in the primary endpoint of incidence of ulcer healing between the NV1FGF and placebo groups (19.4% vs 14.3%; p=0.514). Occurance of any amputation was lower in the NV1FGF group compared with placebo (n=19 vs n=31, hazard ratio [HR] 0.49, p=0.013), as was occurance of major amputation (n=8 vs n=19, HR 0.37, p=0.019). Likewise, time to first major amputation was longer in the NV1FGF group (318 days vs 167 days, p=0.015). Mortality trended lower in the NV1FGF group (n=6 vs n=13, HR 0.46, p=0.11). There was no change in ankle brachial index. The adverse events was similar between groups.

Interpretation:

Among patients with critical limb ischemia, treatment with therapeutic angiogenesis with intramuscular NV1FGF was not associated with a reduction in the primary endpoint of ulcer healing compared with placebo, but was associated with an improvement in the secondary endpoint of amputation.

The present trial, while small, demonstrated favorable results with lower amputation in these no option patients not eligible for revascularization who were treated with therapeutic angiogenesis. A larger phase 3 trial is planned to validate these findings.

References:

Nikol S, Baumgartner I, Van Belle E, et al. Therapeutic angiogenesis with intramuscular NV1FGF improves amputation-free survival in patients with critical limb ischemia. Mol Ther. 2008 May;16(5):972-8. 

Presented by Dr. Sigrid Nikol at the March 2006 ACC Annual Scientific Session, Atlanta, GA.

Keywords: Coronary Artery Disease, Fibroblast Growth Factor 1, Ulcer, Ankle Brachial Index, Plasmids, Injections, Intramuscular, Diabetes Mellitus, Peripheral Vascular Diseases


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