Buflomedil in arterial occlusive disease: results of a controlled multicenter study. Double-blind placebo-controlled trial of buflomedil in the treatment of Raynaud's phenomenon: six-month follow-up. Clinical and hemorheological effects of buflomedil in diabetic subjects with intermittent claudication. A randomized controlled trial of intravesical bacillus calmette-guerin for treatment refractory interstitial cystitis. Comparative study of single-dose and three-day therapy for acute uncomplicated cystitis. Beneficial hemorheologic therapy of chronic peripheral arterial disorders with pentoxifylline: results of double-blind study versus vasodilator-nylidrin. Comparative evaluation of pentoxifylline, buflomedil, and nifedipine in the treatment of intermittent claudication of the lower limbs. N-acetylcysteine has neuroprotective effects against oxaliplatin-based adjuvant chemotherapy in colon cancer patients: preliminary data. A placebo-controlled study of intravesical pentosanpolysulphate for the treatment of interstitial cystitis.
In a double-blind, randomised multicentre study buflomedil, a vasoactive substance, was compared with placebo in the treatment of 93 patients with chronic arterial occlusive disease. After a run-in period of four weeks the patients received either buflomedil (600 mg daily) or placebo over 12 weeks. The pain-free and the total walking distances improved significantly in both groups. However, the differences in the improvement between the two groups were highly significant and in favour of buflomedil: for the pain-free walking distance p less than 0.001 and for the total walking distance p less than 0.01. The results indicate that buflomedil has a beneficial effect on the symptoms and lengthens the walking distance in patients with arterial occlusive disease. The efficacy of buflomedil in reducing the mean daily frequency and severity of winter ischemic attacks has been shown in a randomized, double-blind, placebo-controlled trial including 31 patients (16 in the buflomedil group, 15 in the placebo group) suffering from idiopathic Raynaud's phenomenon and followed up for six months. The efficacy was confirmed by nail fold capillaroscopy, which showed a significant alleviation of hemodymanic disturbances and background pallor in comparison with the placebo. Results in terms of clinical and laboratory safety parameters assessed over a six-month period were satisfactory, thus demonstrating the possibility of a long-term treatment. Changes in blood rheology have been described in diabetes mellitus. Buflomedil, a vasoactive substance with hemorheological properties, has been widely used in the treatment of intermittent claudication. The aim of this study was to evaluate the effect of buflomedil on clinical and hemorheological parameters in subjects with type 2 diabetes and intermittent claudication.
                Forty patients were randomly assigned to oral buflomedil or matching placebo for six months in a double-blind manner. Initial and absolute walking distances were assessed by a standard treadmill testing protocol. Erythrocyte deformability was estimated with a whole blood filtration technique. ADP- and collagen-induced platelet aggregation was assessed with an aggregation profiler. beta-thromboglobulin and platelet factor-4 were measured with radioimmunoassays. All tests were performed at baseline and after three and six months of treatment.
                A significant increase in the mean initial (71%) and absolute (68%) walking distance was achieved only in the buflomedil group. ADP- and collagen-induced platelet aggregation was significantly reduced in the buflomedil group, while no significant changes in erythrocyte deformability, beta-thromboglobulin and platelet factor-4 levels were noticed. However, beta-thromboglobulin levels increased significantly in the placebo group.
                These findings suggest the therapeutic efficacy of buflomedil in diabetic subjects with intermittent claudication. The inhibition of platelet aggregation and the influence on platelet activity exerted by the drug could play an important role in its clinical effect and may be of value in the treatment of such patients. We compared intravesical bacillus Calmette-Guerin (BCG) to placebo instillations in patients with treatment refractory interstitial cystitis (IC).
                Subjects who met the National Institutes of Health-National Institute for Diabetes and Digestive and Kidney Diseases criteria for IC, and reported at least moderate pain and frequency for a minimum of 6 months before study entry, were randomized to 6 weekly double-blinded intravesical instillations of either BCG or placebo, and then followed for a total of 34 weeks. The primary outcome was a patient reported global response assessment at week 34, supplemented with medications for IC during weeks 31 to 34. Secondary outcomes included a 24-hour voiding diary, pain, urgency, validated IC symptom indexes and adverse events. The target sample size was 260 participants, designed to detect a difference in response rates between placebo and BCG of 30% and 50%, respectively.
                A total of 265 participants were randomized and 17 (6%) patients withdrew from study. The response rates for the primary outcome were 12% for placebo and 21% for BCG (p = 0.062). Small improvements were observed for all secondary outcomes, some more so with BCG, but these differences were of borderline statistical significance. Although a large number of adverse events were reported in the BCG arm, there was no statistically significant difference between the treatment arms in overall adverse event rates.
                Although the BCG safety profile was acceptable, the response rate for the primary outcome was low. Effective medical treatment for patients with moderate to severe interstitial cystitis remains elusive. To assess the efficacy and safety of a single-dose therapy for acute uncomplicated cystitis (AUC), we compared 4 treatment regimens in 120 women. Patients eligible for the study were randomly assigned to one of four treatment groups: Ciprofloxacin (CPFX) 200 mg in a single oral dose (group A); 200 mg once daily for 3 days (group B); 200 mg twice daily for 3 day (group C); and cefpodoxime-proxcetil (CPDX-PR) 200 mg once daily for 3 days (group D). The efficacy was evaluated 3 days after the single-dose therapy or at the end of a three-day therapy according to the criteria proposed by the Japanese UTI Committee. The overall clinical efficacy in a total of 107 patients was evaluated to be excellent, moderate, and poor in 72 (67.3%), 35 (31.8%), and 1 (0.9%), respectively. The causative organisms were eradicated in 88.0, 85.2, 85.2, and 82.1% of the patients in groups A, B, C, and D, respectively. Recurrence was identified in 3 (2 in group A and one in group D) of 16 patients who were followed at 2 to 3 weeks after the treatment. No adverse reactions related to the antibiotics were recognized in the study. There were no significant differences in the clinical efficacy or recurrence rate among these four treatment regimens. These results indicate that the single-dose therapy of CPFX is the treatment of choice in women with AUC. Pentoxifylline (Trental 400 mg coated tablets) and nylidrin HCl 3 mg were compared for clinical efficacy and safety in an 8-week randomized double-blind trial. The study was conducted in patients with peripheral arterial disease (Fontaine stage II or III), with 30 patients receiving pentoxifylline (23 returned for follow-up), and 30 patients receiving nylidrin HCl (24 returned for follow-up). Efficacy was assessed objectively in terms of walking performance (absolute walking time and walking distance on a treadmill ergometer) and by acral plethysmography. The clear improvement shown for both variables was greater and statistically significant (p less than or equal to 0.05) after treatment with pentoxifylline. Laboratory data provided no evidence to suggest any adverse effect of either treatment. Subjective side effects were reported by six patients in the pentoxifylline group and by three patients in the nylidrin HCl group. In the light of the current controversy surrounding the use of hemorheologic and vasodilator drugs in the treatment of peripheral arteriosclerosis, a comparative study was designed in order to evaluate the efficacy of pentoxifylline, buflomedil, and nifedipine in 45 patients with peripheral arterial disease (Fontaine stage II). The patients in this prospective randomized study were divided into three groups: 15 patients received pentoxifylline treatment (1,200 mg/day), 15 were treated with buflomedil (600 mg/day), and 15 with nifedipine (60 mg/day). Response to treatment was assessed at the start of the study and after forty-five and ninety days, by clinical examination, Doppler test, strain test, and digital occlusion plethysmography using a strain gauge ring. Pentoxifylline was significantly more effective (P < 0.05) than buflomedil and nifedipine at ninety days in improving walking performance, resting toe pressure, resting and postexercise ankle/brachial pressure ratio, and basal/postischemic toe-pulse ratio. Significant differences within groups were also noted for initial claudication, toe peak-flow time, pulse reappearance time (PRT/2), and maximum postischemic flow time, together with significant intergroup variables. In conclusion, pentoxifylline proved more effective than the other drugs tested in: 1. improving distal pressure and resting microcirculatory blood flow; 2. increasing postexercise distal flow, ratios, and pressures and enabling faster recuperation of basal pulse rates; 3. increasing initial claudication distance in the strain test within the test group and achieving a greater absolute subjective claudication distance than that obtained using the other treatments. Although adding oxaliplatin to fluorouracil and leucovorin in adjuvant chemotherapy for colon cancer may improve disease-free survival, grade 3-4 sensory neuropathy also increases. To determine whether oral N-acetylcysteine is neuroprotective against oxaliplatin-induced neuropathy, we did a pilot study. Fourteen stage III colon cancer patients with 4 or more regional lymph nodes metastasis (N2 disease) receiving adjuvant biweekly oxaliplatin (85 mg/m(2)) plus weekly fluorouracil boluses and low-dose leucovorin were randomized to oral N-acetylcysteine (1,200 mg) (arm A) or placebo (arm B). Clinical neurological and electrophysiological evaluations were performed at baseline and after 4, 8, and 12 treatment cycles. Treatment-related toxicity was evaluated based on National Cancer Institute (NCI) Criteria. After four cycles of chemotherapy, seven of nine patients in arm B and two of five in arm A experienced grade 1 sensory neuropathy. After eight cycles, five experienced sensory neuropathy (grade 2-4 toxicity) in arm B; none in arm A (p<0.05). After 12 cycles, grade 2-4 sensory neuropathy was observed in eight patients in arm B, one in arm A (p<0.05). There were no significant electrophysiological changes in arm A after 4, 8, or 12 cycles of chemotherapy. We concluded that oral N-acetylcysteine reduces the incidence of oxaliplatin-induced neuropathy in colon cancer patients receiving oxaliplatin-based adjuvant chemotherapy. To evaluate the therapeutic efficacy of intravesical pentosanpolysulphate (PPS) compared with placebo in patients with interstitial cystitis (IC).
                Twenty patients who fulfilled the diagnostic criteria for IC participated in a double-blind placebo-controlled study; 10 received intravesical PPS (300 mg in 50 mL of 0.9% sodium chloride) applied twice a week for 3 months and the other 10 received a placebo. Symptomatic relief and objective variables (bladder capacity voiding volumes and urinary frequency) were assessed after 3 months and the long-term outcome of those continuing treatment was determined.
                Of the patients treated with PPS, four gained significant symptomatic relief compared with only two receiving placebo. Only the urodynamic bladder capacity showed a statistically significant increase in patients treated with PPS (P = 0.047). At 18 months from the start of the study, the symptoms were relieved in eight patients while still receiving PPS instillations and in four without treatment.
                These results suggest that intravesical PPS is an effective option for the treatment of IC and shows that the intravesical application of PPS is a safe treatment with no important side-effects.
There is little evidence available to evaluate the efficacy of buflomedil for IC. Most trials were excluded due to poor quality. The two included trials showed moderately positive results; these are undermined by publication bias since we know of at least another four unpublished, irretrievable, and inconclusive studies.
Buflomedil's benefit is small in relation to safety issues and its narrow therapeutic range.