The usefulness of naftidrofuryl in severe peripheral ischaemia--a symptomatic assessment using linear analogue scales. A randomized double-blind controlled trial of naftidrofuryl in acute stroke. Treatment of stage II chronic arterial disease of the lower limbs with the serotonergic antagonist naftidrofuryl: results after 6 months of a controlled, multicenter study. New approach to treatment of recent stroke. Intra-arterial prostacyclin compared to Praxilene in the management of severe lower limb ischaemia: a double blind trial. [Naftidrofuryl in arterial occlusive disease. Controlled multicenter double-blind study with oral administration]. Naftidrofuryl in chronic arterial disease. Results of a six month controlled multicenter study using Naftidrofuryl tablets 200 mg. Towards a model stroke trial. The single-centre naftidrofuryl study. Naftidrofuryl in the treatment of vascular dementia.
The effect of Naftidrofuryl (Nafronyl) on the symptoms of severe peripheral vascular disease has been studied in 40 hospital inpatients. Assessment of ischaemic symptoms and of symptoms which may occur with any type of chronic pain was made using a linear analogue system. Patients treated with naftidrofuryl showed a significant symptomatic improvement compared to patients treated without vasoactive drug therapy. These results show that this drug has a useful place in the treatment of severe ischaemic symptoms during assessment for vascular reconstruction and in those patients found to be unsuitable for limb-salvage operations. There is evidence to support the use of naftidrofuryl in acute stroke with claims of increased recovery, reduced fatality and reduced bed occupancy in patients treated with either oral or intravenous preparations. One hundred patients presenting with acute hemisphere stroke (less than 72 hours) were randomized to receive either a new oral formulation of naftidrofuryl or placebo on a double-blind basis. Treatment was given for a total of 12 weeks and patients followed for 26 weeks with serial neurological and functional assessments by a single observer. Cumulative fatality and hospital-bed occupancy were determined at each assessment interval. No significant difference was demonstrated in cumulative fatality, hospital-bed occupancy or recovery of motor function in patients treated with either naftidrofuryl or placebo. There is no evidence from this study to support the use of oral naftidrofuryl in acute stroke. A study was carried out in patients with intermittent claudication (Fontaine's stage II). The atheromatous origin of the disease was confirmed and localized by angiography or Doppler. One hundred eight-three patients were selected initially (day -30) with a pain-free walking distance on a treadmill (at a speed of 3 km/h and a slope of 10%) ranging from 150 to 300 m. During the first month (washout period) all patients received two placebo tablets daily. At the end of this run-in period (day -30; day 0) and after checking walking distance stability (allowed variation: 20% between the two measurements), patients were included in the study. According to this criterion, 112 patients were selected and 94 remained during the whole study. The study was designed in double-blind, using two parallel, randomly selected groups. Fifty-two patients received naftidrofuryl (2 x 316.5 mg tablets daily with meals) for 6 months; 42 patients received placebo under the same conditions. During this period, clinical and paraclinical examinations were carried out every quarter (day 90 and day 180). After checking the initial homogeneity of the naftidrofuryl and placebo groups, the comparison between the two groups indicates a significant improvement in the naftidrofuryl group after 3 months and 6 months of treatment, for the pain-free walking distance. For the maximal walking distance, a significant improvement was found at day 180. Nonparametric analysis (chi 2 test) also indicated a significant improvement for the naftidrofuryl group. These results confirm that naftidrofuryl is beneficial in the treatment of patients with chronic arterial disease. Ninety-one patients with acute stroke participated in a double-blind, placebo-controlled trial of naftidrofuryl. Treatment was allocated at random and given over 12 weeks, neurological and neurophysical scores being obtained before treatment and at weeks 2, 4, 8, and 12. Both treatment groups greatly improved over the 12 weeks, but the naftidrofuryl-treated patients made greater neurological progress. Of the patients eventually discharged, those given naftidrofuryl spent only half as long in hospital as the controls. Deaths attributable to stroke were significantly fewer in the active-treatment group. The effectiveness of a 72 h. intra-arterial prostacyclin infusion has been compared to that of naftidrofuryl oxalate (Praxilene) in a double blind study of 29 patients with ischaemic rest pain in 30 legs. Long-term relief of symptoms was achieved in 14 legs (47%) and major limb amputation avoided in 18 (60%). No significant difference was demonstrated between the results of prostacyclin infusion and those of Praxilene. The efficacy of naftidrofuryl ( Dusodril ) for treatment of stage II arterial occlusive disease was evaluated in a controlled multi-centre study in a total of 104 out-patients with angiographically documented localization of occlusion. The therapeutic effect was assessed over three months by measurements of walking distance using standardized treadmill conditions. Further parameters were venoocclusive plethysmography and Doppler ultrasonography measurement of pressures. The complaint-free walking distance increased significantly during daily application of 600 mg naftidrofuryl orally (n = 54) during the 12-week assessment period when compared to the placebo group (n = 50). Taking the intraindividual variability of 17.2 m in assessment of walking distance into account, the increase of painless walking of 93 m after treatment for 12 weeks in the active-drug group is considered the result of treatment-induced increased performance. The study was carried out on patients with intermittent claudication (Fontaine's stage II). The arterial and atheromatous origin of the disease was confirmed and localized by angiography or Doppler velocimetry examination. One hundred eighty-six patients were selected initially. Their pain-free walking distance on a treadmill (at a speed of 3 km/hour and an inclination of 10%) had to be 150-300 m. During the first month all patients received 3 placebo tablets daily. At the end of this run-in period (D-30; D 0) and after checking walking distance stability (allowed variation: +/- 20% between the two measurements) the patients were included in the study. One hundred fifty-four patients were selected and 118 remained during the whole study. The study was designed as a double-blind, using two parallel randomly selected groups. Sixty-four patients received for six months Naftidrofuryl (3 X 200 mg tablets daily with meals); 54 patients received placebo under the same conditions. During this period, clinical and paraclinical examinations were carried out every quarter (D 90 and D 180). After checking the initial homogeneity of the Naftidrofuryl and placebo-groups, the comparison between groups indicates a significant improvement in Naftidrofuryl group after 3 and 6 months of treatment. At the end of the study the observed differences in walking distance with Naftidrofuryl are approximately twice the difference in the reference group (D 90: p less than 0.05; D 180: p less than 0.02). The results of this study indicate that Naftidrofuryl is an efficient pharmacological tool for treatment of patients with chronic arterial disease (Fontaine's stage II). It has been questionable whether the lack of proven pharmacological treatments in acute cerebral infarction (ACI) reflects ineffective drugs or only inadequacies in their assessment. The difficulties in developing a rationale for drug therapy in this condition favoured the former, although the latter possibility was supported by re-evaluation of most published trials. In this paper, a plausible rationale, in terms of our current understanding of both the drug and the condition, is expounded for treatment of ACI with naftidrofuryl. Guidelines for the design and conduct of clinical trials in acute stroke are discussed in relation to the particular problems posed: need for early initiation of treatment; need for, and difficulties of, diagnostic confirmation; matching of treatment groups by prognostic indicators of uncertain significance, and requirements for large numbers of patients and long-term follow-up. The practical application of these guidelines is tested in a clinical trial of naftidrofuryl conducted in a single centre on 100 patients with proven diagnoses. Rigorous attention to all aspects of selection, treatment and follow-up, with an explanatory approach to the trial design, was predicted to produce a positive result if the drug was effective. The findings were that naftidrofuryl treatment was associated with no change in death rate but with clinically and statistically significant improvements in neurological recovery and bed-occupancy. Better functional recovery was also noted, so that the trial result was coherent. It was concluded that a beneficial effect had been recorded, and consistency of this outcome with those of previous studies is demonstrated. A case is made for further studies to define exactly the role of this drug in the management of ACI. The design of this study was based on the European guidelines for the treatment of Alzheimer's disease. After a placebo run-in period of 4 weeks, patients with a diagnosis of vascular dementia (VaD) were randomised to receive either 400 mg naftidrofuryl/day, 600 mg naftidrofuryl/day or placebo for 6 months. The patients were assessed using the ADAS-cog, the SCAG, the NOSGER and the CGI item 2 scale. The primary analysis was undertaken on the ITT population. At the end of the study, significantly more patients in the treatment groups showed no deterioration on both ADAS-cog and SCAG scales compared with placebo (400 mg p = 0.005, 600mg p = 0.015). There were also significant differences between the active and placebo groups for the individual scales. This study has demonstrated that treatment with naftidrofuryl can slow the rate of deterioration of patients with vascular dementia.
Based on the results of these trials, it cannot be confirmed that intravenous naftidrofuryl is effective in the treatment of people with critical limb ischaemia. However, these results were based on trials of generally low methodological quality which had only a small number of participants, the duration of treatment was extremely short, and the methods varied between the trials. The wide range of endpoints effectively precluded any meaningful pooling of the results. Intravenous naftidrofuryl was withdrawn as a treatment for severe peripheral arterial disease in 1995 because of reported side effects.