纖維原細胞生長因數可以改善患者嚴重跛行的症狀

對血管的效果,可以使患者不必接受脈管切除和脈管旁路手術的治療

  2002年6月14日報導─據《Lancet》雜誌6月15日一期中報導的TRAFFIC研究的結果顯示,重組的纖維原細胞生長因素-2(rFGF-2)可以促進血管增生,並且使那些要接受切除或其肢體血管旁路已經不可能形成的患者的嚴重的跛行症狀得到改善。

  在新聞發表會上,主要作者,Durham, N.C. Duke大學醫學部的醫師Brian Annex:「血管形成是一個研究非常活躍的領域,有著廣大的研究前景。這項研究的結果提示了最強的和最可信的結果,提示血管生成因數對人類有著正向的作用。它還是一個利用隨機安慰劑對照的臨床試驗來獲得的陽性結果,從而加速進一步研究的進行。由於這項研究首次利用主要的臨床終點作為研究的結果,而獲得了陽性的結果,因此為這方面的研究提供了重要的基礎。」

  利用治療性FGF促進血管生成來治療間歇性跛行(TRAFFIC)研究是一項多中心的,II期,雙盲對照實驗,共募集了190名由於小腿肌肉動脈硬化症,所導致的間歇性跛行的患者。

  被隨機分配進入對照組的被研究者,在治療的第1天和第30雙側接受雙側動脈內灌注安慰劑,被分配進入單劑量組的患者在治療的第1天灌注rFGF-2 (30 mcg/kg),在治療的第30天灌注安慰劑,被分配進入雙劑量組的被研究者在治療的第1天和第30天灌注rFGF-2 (30 mcg/kg)。患者蛋白尿的嚴重程度與接受注射的劑量有關,在安慰劑組蛋白尿的發生率為2%,單劑量組的發生率為5%,雙劑量組的發生率為8%。

  在治療的第90天,安慰劑組患者最長的行走時間延長了14%(0.6分鐘),單劑量組患者延長了34%(1.77分鐘),而雙劑量組患者延長了20%(1.54分鐘)(單劑量組與對照組相比P=0.26)。儘管血管形成、連接和血管的接通的機理還不清楚,但是踝臂壓指數的改善也暗示將有助於患者肢端血流的灌注。

  主要作者,密西根大學醫學部心血管疾病部門的Robert Lederman醫師說:「動脈內rFGF-2的可以在治療的第90天,顯著的延長患者的最長行走時間。在治療的第30天重覆注射rFGF-2,其效果並不比一次注射的效果好。TRAFFIC的研究發現,為臨床血管內注射血管形成蛋白,從而治療性的促進血管形成提供了證據。」

  但是作者提出了研究的侷限性和應注意的地方,這項研究的結果不能應用於在血液動力學上出現髂骨動脈狹窄的患者中。

  在編者附錄中,英國諾丁漢大學的醫學教授,Richard Donnelly說:「當患者的血管再造手術不能實行或出現失敗,或患者發生嚴重貧血和末端動脈斷裂的危險性非常大時,在下肢進行治療性的血管形成術會特別有效。」

Fibroblast Growth Factor Improves Severe Claudication

Angiogenic Effect May Help Avoid Amputation, Bypass

By Laurie Barclay, MD
WebMD Medical News

Reviewed by Gary D. Vogin, MD

June 14, 2002 -- Recombinant fibroblast growth factor-2 (rFGF-2) may enhance angiogenesis and improve severe claudication in patients at high risk for amputation or in whom bypass is not feasible, according to results of the TRAFFIC study reported in the June 15 issue of The Lancet.

"Angiogenesis is an extremely exciting area with a great deal of potential. This study provides the strongest and most convincing data to date that an angiogenic agent can have a positive effect in humans," senior author Brian Annex, MD, from Duke University Medical Center in Durham, N.C., said in a news release. "It is also one that has been in need of positive randomized, placebo-controlled data to accelerate further research. This study is an important step in that direction, [as it is] the first to show a positive result in its primary endpoint."

The Therapeutic Angiogenesis with FGF for Intermittent Claudication (TRAFFIC) study was a multicenter, phase II, double-blinded, controlled trial enrolling 190 patients with intermittent claudication of the calf muscle caused by atherosclerosis.

Subjects were randomly assigned to a control group receiving bilateral intra-arterial infusions of placebo on days 1 and 30; a single-dose group receiving rFGF-2 (30 mcg/kg) on day 1 and placebo on day 30; or a double-dose group receiving rFGF-2 (30 mcg/kg) on days 1 and 30. Severe proteinuria appeared to be dose-related, occurring in 2% of patients in the placebo group, 5% in the single-dose group, and 8% in the double-dose group.

At 90 days, peak walking time increased by 14% (0.6 minutes) in the placebo group, by 34% (1.77 minutes) in the single-dose group, and by 20% (1.54 minutes) in the double-dose group (P=.026 for single-dose relative to placebo). Improved scores in the ankle-brachial pressure index also suggest that rFGF-2 improved limb perfusion, although whether the mechanism involves angiogenesis, collateralization, or recanalization is not entirely clear.

"Intra-arterial rFGF-2 resulted in a significant increase in peak walking time at 90 days; repeat infusion at 30 days was no better than one infusion," said lead author Robert Lederman, MD, of the division of cardiology at the University of Michigan Health System. "The findings of TRAFFIC provide evidence of clinical therapeutic angiogenesis by intra-arterial infusion of an angiogenic protein."

However, the authors note study limitations and caution that the findings may not apply to patients with hemodynamically significant iliac stenosis.

In an accompanying commentary, Richard Donnelly, professor of medicine at the University of Nottingham, England, notes that "therapeutic angiogenesis in the lower limb would be especially attractive when revascularization is not feasible or has failed, or when the risks of critical ischemia and distal amputation are high."

© 2002 WebMD Inc. All rights reserved.

    
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