Randomized, placebo-controlled trial of low molecular weight heparin in active ulcerative colitis. Direct comparison of two different mesalamine formulations for the induction of remission in patients with ulcerative colitis: a double-blind, randomized study. Safety and efficacy of a new 3.3 g b.i.d. tablet formulation in patients with mild-to-moderately-active ulcerative colitis: a multicenter, randomized, double-blind, placebo-controlled study. Clinical trial: oral colon-release parnaparin sodium tablets (CB-01-05 MMX) for active left-sided ulcerative colitis. Different therapy for different types of ulcerative colitis in China. Delayed-release oral mesalamine 4.8 g/day (800-mg tablet) is effective for patients with moderately active ulcerative colitis. Clinical trial: once-daily mesalamine granules for maintenance of remission of ulcerative colitis - a 6-month placebo-controlled trial. An open-label, comparative study of the efficacy and safety of once-daily dose of enoxaparin versus unfractionated heparin in the treatment of proximal lower limb deep-vein thrombosis. Topical treatment of distal active ulcerative colitis with beclomethasone dipropionate or mesalamine: a single-blind randomized controlled trial.
In several open and 1 controlled trial, unfractionated heparin was effective in the treatment of active ulcerative colitis (UC). Low molecular weight heparin (LMWH) had a similar effect in several open studies.
                We studied the efficacy, safety, and tolerability of LMWH in mild to moderately active UC in a randomized, double-blind, placebo-controlled trial. In all, 29 patients with a mild or moderate recurrence of UC during salicylate treatment were randomized to receive either reviparin 3,436 IU (n = 15) subcutaneously twice daily or placebo (n = 14). The study period was 8 weeks. Treatment was discontinued if there was no improvement at 4 weeks or at any disease progression. Primary outcome measure was clinical improvement at 8 weeks measured by the Colitis Activity Index (CAI) and the Clinical Symptoms Grading (CSG, based on the CAI). Endoscopic and histologic grading and quality of life as measured by the Inflammatory Bowel Disease Questionnaire (IBDQ) were secondary outcome measures. Patients were closely monitored for adverse events.
                Twenty of 29 patients finished the 8-week treatment period (reviparin versus placebo: 11 versus 9; P = 0.70). There was no difference in CSG, CAI, endoscopic and histologic grading, or IBDQ. Treatment was well tolerated and no serious adverse events occurred.
                In this study, treatment with LMWH showed no significant clinical advantage compared to placebo in mild to moderately active UC. Mesalamine is the first-line drug for the treatment of ulcerative colitis (UC). We directly compared the efficacy and safety of two mesalamine formulations for the induction of remission in patients with UC.
                In a multicenter, double-blind, randomized study, 229 patients with mild-to-moderate active UC were assigned to 4 groups: 66 and 65 received a pH-dependent release formulation of 2.4 g/day (pH-2.4 g) or 3.6 g/day (pH-3.6 g), respectively; 65 received a time-dependent release formulation of 2.25 g/day (Time-2.25 g), and 33 received placebo (Placebo). The drugs were administered three times daily for eight weeks. The primary endpoint was a decrease in the UC disease activity index (UC-DAI).
                In the full analysis set (n = 225) the decrease in UC-DAI in each group was 1.5 in pH-2.4 g, 2.9 in pH-3.6 g, 1.3 in Time-2.25 g and 0.3 in Placebo, respectively. These results demonstrate the superiority of pH-3.6 g over Time-2.25 g (P = 0.003) and the noninferiority of pH-2.4 g to Time-2.25 g. Among the patients with proctitis-type UC, a significant decrease in UC-DAI was observed in pH-2.4 g and pH-3.6 g as compared to Placebo, but not in Time-2.25 g. No differences were observed in the safety profiles.
                Higher dose of the pH-dependent release formulation was more effective for induction of remission in patients with mild-to-moderate active UC. Additionally, the pH-dependent release formulation was preferable to the time-dependent release formulation for patients with proctitis-type UC (UMIN Clinical Trials Registry, no. C000000288). To evaluate the safety and efficacy of a new twice-daily balsalazide disodium 1.1 g tablet dosing regimen (6.6 g/day, three tablets twice daily) for the treatment of mild-to-moderately-active ulcerative colitis (UC).
                In a double-blind, multicenter study patients with symptoms of acute UC and a baseline Modified Mayo Disease Activity Index (MMDAI) score between 6 and 10, inclusive, with a subscale rating of > or =2 for both rectal bleeding and mucosal appearance were randomized to receive 3.3 g of balsalazide or placebo tablets twice daily for 8 weeks. The primary end point was the proportion of patients achieving clinical improvement (> or =3 point improvement in MMDAI) and improvement in rectal bleeding (> or =1 point improvement) at 8 weeks. Safety assessments were conducted from baseline through 2-weeks post-treatment.
                A total of 249 patients (166 balsalazide, 83 placebo) received at least 1 dose of study medication. The mean MMDAI score at baseline was 7.9; 62% of patients had a score > or =8.0 (moderate disease). A significantly larger proportion of patients achieved clinical improvement and improvement in rectal bleeding in the balsalazide group vs. the placebo group (55 vs. 40%, P=0.02). The most common adverse events reported were worsening of UC and headache; both were reported more often in the placebo group.
                Balsalazide disodium 1.1 g tablets administered as 3.3 g twice daily are effective, well tolerated and significantly better than placebo for improving signs and symptoms of mild-to-moderately-active UC. This new formulation with a reduced pill and dosing burden offers the potential to improve convenience and compliance in patients with active UC. The administration of parnaparin sodium as oral colon-release tablets (CB-01-05 MMX) has been proposed as a novel approach for the treatment of ulcerative colitis (UC).
                To assess the efficacy and the tolerability of 8 weeks' oral daily administration of 210 mg of parnaparin sodium compared with placebo in subjects treated with stable-doses of oral aminosalicylates.
                This multicenter, randomized, double-blind proof of concept trial compared the efficacy of CB-01-05 MMX 210 mg tablets to placebo in 141 subjects with mild to moderately active left-sided UC treated with stable-doses of aminosalicylates. The efficacy was assessed by clinical activity index (CAI), endoscopic index (EI) and histological score (HS).
                A total of 121 subjects (61 in test group and 60 in control group) formed the per protocol (PP) population. After 8 weeks of treatment, clinical remission was achieved in 83.6% of the CB-01-05 MMX group, and in 63.3% in the comparator group (P = 0.011). This effect was also significantly evident in the test group at week 4 (P = 0.028). A significant difference was also detected in rectal bleeding, (disappeared respectively in 75.4% and 55.0%; P = 0.018), and in mucosal friability (recovered respectively in 80.3% and in 56.7%; P = 0.005).
                CB-01-05 MMX was safe and significantly effective in treating subjects with mild-to-moderate left-sided UC treated with stable-doses of aminosalicylates. To study the different therapy for different types of ulcerative colitis (UC) in China.
                Among 102 UC patients, 42 chronic relapse type UC patients were randomly divided into olsalazine sodium treatment group (n=21) and SASP group (n=21). Clinical effects and safety were observed in the 2 groups. Forty-two first episode type UC patients were randomly divided into Heartleaf houttuynia herb treatment group (n=21) and SASP group (n=21). Clinical effects were observed in the 2 groups while ultrastructure of colonic mucosa, ICAM-1 and the pressure of distant colon were studied in Heartleaf houttuynia herb group. Eighteen patients (8 males, 10 females) with refractory UC and unresponsive to high-dose prednisolone and sulfasalazine therapy more than one month were treated with Kangshuanling (7200 U/d). Prednisolone was gradually stopped and sulfasalazine was maintained. Stool frequency, rectal bleeding, colonoscopy, general well-being, histology were observed and CD62p, CD63, CD54, Pgp-170 (flow cytometry), TXA2 (RIA), blood platelet aggregation rate and thrombosis length in vitro were assessed.
                In the 42 chronic relapse type UC patients, the overall clinical effects of olsalazine sodium group (complete remission in 16, improvement in 4, inefficiency in 1) were better than those of SASP group (complete remission in 10, improvement in 4, inefficiency in 7, P<0.05). Symptomatic remission of olsalazine sodium group (complete remission in 15, partial remission in 5, inefficiency in 1) was better than that of SASP group (complete remission in 10, partial remission in 5, inefficiency in 6, P<0.05). The colonoscopic remission of olsalazine sodium group(complete remission in 11, partial remission in 9, inefficiency in 1) was better than that of SASP group (complete remission in 7, partial remission in 8, inefficiency in 6, P<0.05). The histologic remission of olsalazine sodium group (complete remission in 13, partial remission in 7, inefficiency in in 1) was better than that of SASP group (complete remission in 6, partial remission in 10, inefficiency in 5, P<0.05). The side effects of gastrointestinal tract in olsalazine sodium group were less than those of SASP group except for frequency of watery diarrhea. No other side effects were observed in olsalazine sodium group while ALT increase, WBC decrease and skin eruption were observed in SASP group. Two patients relapsed in olsalazine sodium group while 8 cases relapsed in SASP group during the flow-up period (from six months to one year). In the 42 first episode type UC patients, the clinical effect of Heartleaf houttuynia herb group (complete remission in 20, 95.2%; improvement in 1, 4.8%) was better than that of SASP group (complete remission in 15, 72.4%, improvement in 5, 23.8%; inefficiency in 1, 3.8%, P<0.01). The time of stool frequency recovering to normal (5.6+/-3.3 d), and blood stool disappearance (6.7+/-3.8 d) and abdominal pain disappearance (6.1+/-3.5 d) in Heartleaf houttuynia herb group was all shorter than that in SASP group (9.5+/-4.9 d, 11.7+/-6.1 d, 10.6+/-5.3 d, P<0.01). Heartleaf houttuynia herb could inhibit the epithelial cell apoptosis of colonic mucous membrane and the expression of ICAM-1 (45.8+/-5.7% vs 30.7+/-4.1%, P<0.05). Compared with normal persons, the mean promotive speed of contraction wave stepped up (4.6+/-1.6 cm/min vs 3.2+/-1.8 cm/min, P<0.05) and the mean amplitude of the wave decreased (14.2+/-9.3 kPa vs 18.4+/-8.0 kPa, P<0.05) in active UC patients. After treatment with Heartleaf houttuynia herb, these 2 indexes improved significantly (17.3+/-8.3 kPa, 3.7+/-1.7 cm/min, P<0.05). In normal persons, the postprandial pressure of sigmoid (2.9 +/-0.9 kPa) was higher than that of descending colon (2.0+/-0.7 kPa) and splenic flexure (1.7+/-0.6 kPa), while the colonic pressure (1.5+/-0.5 kPa, 1.4+/-0.6 kPa, 1.3+/-0.6 kPa) decreased significantly (P<0.05) in active UC patients. After treatment with Heartleaf houttuynia herb, the colonic pressure (2.6+/-0.8 kPa, 1.8+/-0.6 kPa, 1.6+/-0.5 kPa) recovered to normal. The pain threshold Heartleaf houttuynia herb, the colonic pressure (2.6+/-0.8 kPa, 1.8+/-0.6 kPa, 1.6+/-0.5 kPa) recovered to normal. The pain threshold of distant colon (67.3+/-18.9 mL) in active UC patients decreased significantly compared with that of normal persons (216.2+/-40.8 mL, P<0.05) and recovered to normal after treatment with Heartleaf houttuynia herb(187.4+/-27.2 mL, P<0.05). In the 18 refractory UC patients with platelet activation, after more than 4 wk of combined Kangshuanling and sulfasalazine therapy, 16 patients achieved clinical remission, with a highly significant statistical difference (P<0.01) between pre-and post-treatment mean scores for all disease parameters: stool frequency (8.2/d vs 1.6/d), rectal bleeding (score 2.7 vs 0.3), colonoscopy (score 2.6 vs 1.1), histology (score 12.0 vs 5.0), general well being (score 4.0 vs 0.6) and CD62p (8.0+/-3.1% vs 4.1+/-1.8%), CD63 (6.3+/-2.1% vs 3.2+/-1.6%), TXA2 (548+/-85 ng/L vs 390+/-67 ng/L), platelet aggregation rate (43.2+/-10.7% vs 34.8+/-8.1%), thrombosis length in vitro (2.3+/-0.6 cm vs 1.8+/-0.3 cm), CD54 in blood (26.9+/-6.9% vs 14.4+/-5.1%), CD54 in tissues (51.1+/-6.2% vs 23.1+/-4.1%), Pgp-170 in blood (18.9+/-3.9% vs 10.4+/-2.7%), Pgp-170 in tissues (16.5+/-3.2% vs 10.2+/-2.3%, P<0.01 or 0.05).
                Based on the characteristics of UC cases in China, different therapy should be given to different types of UC with expected satisfactory results. It is not clear what induction dose of mesalamine is optimal for treating patients with mildly and moderately active ulcerative colitis (UC). This study was conducted to determine the efficacy and safety of mesalamine 4.8 g/day compared with 2.4 g/day for the treatment of moderately active UC.
                A multicenter, randomized, double-blind, 6-week, active-control study (ASCEND III) was conducted to assess the noninferiority of delayed-release mesalamine 4.8 g/day (Asacol HD, 800-mg tablet; Procter & Gamble, Pharmaceuticals, Inc, Mason, Ohio) with 2.4 g/day (Asacol, 400-mg tablet; Procter & Gamble Pharmaceuticals, Inc) in 772 patients with moderately active UC. The primary endpoint was treatment success (overall improvement) at week 6, defined as improvement in the Physician's Global Assessment (based on clinical assessments of rectal bleeding, stool frequency, and sigmoidoscopy), with no worsening in any individual clinical assessment.
                The primary objective of noninferiority was met. Seventy percent (273 of 389) of patients who received 4.8 g/day of mesalamine achieved treatment success at week 6, compared with 66% (251 of 383) of patients receiving 2.4 g/day (95% confidence interval for 2.4 g/day minus 4.8 g/day, -11.2 to 1.9). In addition, 43% of patients who received 4.8 g/day mesalamine achieved clinical remission at week 6 compared with 35% of patients who received 2.4 g/day (P = .04). A therapeutic advantage for the 4.8 g/day dose was observed among patients previously treated with corticosteroids, oral mesalamines, rectal therapies, or multiple UC medications. Both regimens were well-tolerated with similar adverse events.
                Delayed-release mesalamine 4.8 g/day (800-mg tablet) is efficacious and well-tolerated in patients with moderately active UC. Ulcerative colitis (UC) is a chronic relapsing and remitting idiopathic inflammatory bowel disorder.
                To evaluate once-daily mesalamine (mesalazine) granules (MG) for maintenance of remission of UC.
                Randomized, double-blind, placebo-controlled trial of patients (n=209 MG, n=96 placebo) with UC in remission [revised Sutherland Disease Activity Index (SDAI) rectal bleeding=0, mucosal appearance <2] who took MG 1.5 g or placebo once-daily for up to 6 months. Primary efficacy endpoint: the percentage of patients who remained relapse-free at month 6/end of treatment. Relapse was defined as SDAI rectal bleeding score ≥1 and a mucosal appearance score ≥2, a UC flare, or initiation of medication to treat a UC flare.
                The percentage of relapse-free patients at month 6/end of treatment was higher with MG than placebo (78.9% vs. 58.3%, P < 0.001) in the intent-to-treat analysis. Significant differences (P ≤ 0.025) favouring MG were observed for most secondary endpoints including improvement in rectal bleeding, physician's disease activity rating, stool frequency, the SDAI at month 6/end of treatment, patients classified as a treatment success and relapse-free duration. The incidence of adverse events was similar between groups.
                Once-daily mesalamine (mesalazine) was effective in maintaining remission of UC for 6 months.
                © 2010 Salix Pharmaceuticals. Treatment of deep-vein thrombosis (DVT) with a once-daily regimen of enoxaparin, rather than a continuous infusion of unfractionated heparin (UFH) is more convenient and allows for home care in some patients. This study was designed to compare the efficacy and safety of these two regimens for the treatment of patients with proximal lower limb DVT.
                201 patients with proximal lower limb DVT from 13 centers in Brazil were randomized in an open manner to receive either enoxaparin [1.5 mg/kg subcutaneous (s.c.) OD] or intravenous (i.v.) UFH (adjusted to aPTT 1.5-2.5 times control) for 5-10 days. All patients also received warfarin (INR 2-3) for at least 3 months. The primary efficacy endpoint was recurrent DVT (confirmed by venography or ultrasonography), and safety endpoints included bleeding and serious adverse events. The rate of pulmonary embolism (PE) was also collected. Hospitalization was at the physician's discretion.
                Baseline patient characteristics were comparable between groups. The duration of hospital stay was significantly shorter with enoxaparin than with UFH (3 versus 7 days). In addition, 36% of patients receiving enoxaparin did not need to be hospitalized, whereas all of the patients receiving UFH were hospitalized. The treatment duration was slightly longer with enoxaparin (8 versus 7 days). There was a nonsignificant trend toward a reduction in the rate of recurrent DVT with enoxaparin versus UFH, and similar safety.
                A once-daily regimen of enoxaparin 1.5 mg/kg subcutaneous is at least as effective and safe as conventional treatment with a continuous intravenous infusion of UFH. However, the once daily enoxaparin regimen is easier to administer (subcutaneous versus intravenous), does not require aPTT monitoring, and leads to both a reduced number of hospital admissions and an average 4-day-shorter hospital stay. Therapy for active ulcerative colitis (UC) usually involves rectal formulations of corticosteroids (CS), which are characterized by the risk of systemic steroid-related adverse effects.
                To compare the efficacy and safety of the topically acting CS beclomethasone dipropionate (BDP) versus mesalamine (5-ASA) in the treatment of active UC.
                Patients with mild to moderate distal active UC were randomized to a 6-week treatment with BDP 3 mg enema o.d. or 5-ASA 1 g enema daily in a single-blind, multicenter, parallel-group, controlled study. The primary efficacy variable was the decrease in Disease Activity Index (DAI) score. Safety variables were adrenal function, monitoring of adverse events, vital signs, and laboratory parameters.
                A total of 217 patients were enrolled and treated with BDP (n = 111) or 5-ASA (n = 106). A significant decrease in the DAI score (P < 0.05) was observed in both treatment groups, with a clinical remission rate of 36.7% in the BDP group and of 29.2% in the 5-ASA group. Both treatments were well tolerated. No changes from baseline in morning cortisol levels were observed in the BDP group.
                BDP administered as a rectal enema over a 6-week treatment period was efficacious and safe in patients with active UC, without interference with pituitary adrenal axis.
There is evidence to suggest that LMWH may be effective for the treatment of active UC. When administered by extended colon-release tablets, LMWH was more effective than placebo for treating outpatients with mild to moderate disease. This benefit needs to be confirmed by further randomized controlled studies. The same benefits were not seen when LMWH was administered subcutaneously at lower doses. There is no evidence to support the use of UFH for the treatment of active UC. A further trial of UFH in patients with mild disease may also be justified. Any benefit found would need to be weighed against a possible increased risk of rectal bleeding in patients with active UC.