First-dose analgesic effect of the cyclo-oxygenase-2 selective inhibitor lumiracoxib in osteoarthritis of the knee: a randomized, double-blind, placebo-controlled comparison with celecoxib [NCT00267215]

Cyclo-oxygenase-2 selective inhibitors are frequently used to manage osteoarthritis. We compared the analgesic efficacy of the novel cyclo-oxygenase-2 selective inhibitor lumiracoxib (Prexige) versus placebo and celecoxib in patients with knee osteoarthritis. This seven day, double-blind, placebo and active comparator controlled, parallel group study included 364 patients aged > or = 50 years with moderate-to-severe symptomatic knee osteoarthritis. Patients received lumiracoxib 400 mg/day (four times the recommended chronic dose in osteoarthritis; n = 144), placebo (n = 75), or celecoxib 200 mg twice daily (n = 145). The primary variable was actual pain intensity difference (100 mm visual-analogue scale) between baseline and the mean of three hour and five hour assessments after the first dose. Actual pain intensity difference, average and worst pain, pain relief and functional status (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]) were measured over seven days. Patients also completed a global evaluation of treatment effect at study end or premature discontinuation. For the primary variable, the superiority of lumiracoxib versus placebo, the noninferiority of lumiracoxib versus celecoxib, and the superiority of lumiracoxib versus celecoxib were assessed by closed test procedure adjusting for multiplicity, thereby maintaining the overall 5% significance level. In addition, celecoxib was assessed versus placebo in a predefined exploratory manner to assess trial sensitivity. Lumiracoxib provided better analgesia than placebo 3-5 hours after the first dose (P = 0.004) through to study end. The estimated difference between lumiracoxib and celecoxib 3-5 hours after the first dose was not significant (P = 0.185). Celecoxib was not significantly different from placebo in this analysis (P = 0.069). At study end 13.9% of lumiracoxib-treated patients reported complete pain relief versus 5.5% and 5.3% of celecoxib and placebo recipients, respectively. WOMAC total and subscales improved for both active treatments versus placebo except for difficulty in performing daily activities, for which celecoxib just failed to achieve significance (P = 0.056). In the patient's global evaluation of treatment effect, 58.1% of patients receiving lumiracoxib rated treatment as 'excellent' or 'good', versus 48.6% of celecoxib and 25.3% of placebo patients. Lumiracoxib was well tolerated. The overall incidence of adverse events was similar across treatment groups.     

Chemotherapy-induced chromosomal damage in peripheral blood lymphocytes of cancer patients supplemented with antioxidants or placebo.

A total of 27 patients with various types of cancer were treated with cisplatin-based combination chemotherapy. Out of these, 13 patients were randomized to receive supplementation treatment with a beverage containing the antioxidants vitamins C and E, plus selenium, during chemotherapy. The antioxidant mixture was administered to investigate whether it could reduce the potential genotoxic and nephrotoxic effect of the applied chemotherapy. A placebo group of 14 cancer patients received a beverage without selenium or antioxidants. Micronuclei (MN) in cytochalasin B-blocked binucleate (BN) peripheral blood lymphocytes (PBLs) and hypoxanthine phosphoribosyl transferase (HPRT) mutants in PBLs were studied before, during and after chemotherapy as a measure for chemotherapy-induced genotoxic effects.Before chemotherapy, patients mean frequencies of MN and HPRT mutants did not differ from those in a group of 10 healthy subjects. The mean frequency of MN in patients increased significantly after one cycle of chemotherapy (P=0.002). This frequency was still elevated at 2 months after the completion of chemotherapy (not significantly). There was no significant difference in micronuclei frequency (MNF) between the antioxidant and placebo group of patients. Chemotherapy-induced frequencies of MN after three cycles of chemotherapy correlated significantly with the cumulative dose of cisplatin (r=0.58, P=0.012) and the cisplatin-mediated loss of renal function (r=0.53, P=0.03). No consistent change in HPRT mutant frequency following chemotherapy was observed in the placebo and antioxidant group of patients. In conclusion, cisplatin-combination chemotherapy resulted in a cisplatin dose-related increase of the frequency of chromosomal damage. Supplementation with antioxidants did not prevent or reduce this effect.     

A Multicenter,Randomized, Double-Blind,Placebo-Controlled Trial of High-Dose Rebamipide Treatment for Low-Dose Aspirin-Induced Moderate-to-Severe Small Intestinal Damage

Background

Low-dose aspirin (LDA) frequently causes small bowel injury. While some drugs have been reported to be effective in treating LDA-induced small intestinal damage, most studies did not exclude patients with mild damage thought to be clinically insignificant.

Aim

We conducted a multicenter, randomized, double-blind, placebo-controlled trial to assess the efficacy of a high dose of rebamipide, a gastroprotective drug, for LDA-induced moderate-to-severe enteropathy.

Methods

We enrolled patients who received 100 mg of enteric-coated aspirin daily for more than 3 months and were found to have more than 3 mucosal breaks (i.e., erosions or ulcers) in the small intestine by capsule endoscopy. Eligible patients were assigned to receive either rebamipide 300 mg (triple dose) 3 times daily or placebo for 8 weeks in a 2:1 ratio. Capsule endoscopy was then repeated. The primary endpoint was the change in the number of mucosal breaks from baseline to 8 weeks. Secondary endpoints included the complete healing of mucosal breaks at 8 weeks and the change in Lewis score (an endoscopic score assessing damage severity) from baseline to 8 weeks.

Results

The study was completed by 38 patients (rebamipide group: n = 25, placebo group: n = 13). After 8 weeks of treatment, rebamipide, but not placebo, significantly decreased the number of mucosal breaks (p = 0.046). While the difference was not significant (p = 0.13), the rate of complete mucosal break healing in the rebamipide group (32%, 8 of 25) tended to be higher than that in the placebo group (7.7%, 1 of 13). Rebamipide treatment significantly improved intestinal damage severity as assessed by the Lewis score (p = 0.02), whereas placebo did not. The triple dose of rebamipide was well tolerated.

Conclusions

High-dose rebamipide is effective for the treatment of LDA-induced moderate-to-severe enteropathy.

Trial Registration

UMIN Clinical Trials Registry UMIN000003463     

A case report of the successful treatment of recurrent aphthous stomatitis with some preparations of orally administered transfer factor

A patient with severe disabling recurrent aphthous stomatitis (RAS) was treated with four different preparations of oral human transfer factor (TF), as well as placebo, following a double-blind protocol. Two of the TF preparations had a significant effect upon the course of the patient's illness by prolonging the interval between attacks and decreasing the severity of attacks. No side effects attributable to any of the preparations were noted by the patient. Thus, some but not all preparations of human transfer factor given orally are an effective therapy for RAS.     

Chronic recurrent aphthous stomatitis: oral treatment with low-dose interferon alpha

Recombinant human interferon alfa-2a (HuIFN alpha) was administered orally once daily in a low concentration (1,200 IU/day) to nine patients with chronic recurrent aphthous stomatitis (RAS), and a placebo solution was given to 10 control chronic RAS patients in a double-blind study. All HuIFN alpha-treated patients had total remission of their aphthae within a 2-week period, while placebo control patients had no change in their condition. The 10 placebo control patients were then treated with HuIFN alpha in a manner identical to that used for the initial principal group. Within a 2-week period, all original placebo patients had complete remission of their aphthae. Eleven of the patients did not have a recurrence of RAS during a subsequent 6-month observation period. Eight patients had recurring aphthae; however, the lesions were resolved by retreating with oral HuIFN alpha for less than 1 week.     

Albendazole chemotherapy for treatment of diarrhoea in patients with AIDS in Zambia: a randomised double blind controlled trial.

OBJECTIVE--To determine the value of short course, high dose albendazole chemotherapy in the treatment of persistent diarrhoea related to HIV in unselected patients in urban Zambia. DESIGN--A randomised double blind placebo controlled trial of albendazole 800 mg twice daily for two weeks. Patients were monitored intensively for one month and followed for up to six months. SETTING--Home care. AIDS services in Lusaka and Ndola. PATIENTS--174 HIV seropositive patients with persistent diarrhoea (defined as loose but not bloody stools three or more times a day for three weeks or longer). No investigations were undertaken except HIV testing after counselling. MAIN OUTCOME MEASURES--Proportion of time periods during which diarrhoea was experienced after completion of treatment; proportion of patients with full remission after completion of treatment; mortality. RESULTS--The patients taking albendazole had diarrhoea on 29% fewer days than those taking placebo (P < 0.0001) in the two weeks after treatment. The benefit of albendazole was maintained over six months. In patients with a Karnofsky score of 50 to 70 (needing help with activities of daily living and unable to work, but not needing admission to hospital) diarrhoea was reduced by 50%. Remission was obtained in 26% of all patients who received albendazole (P = 0.004 against 9% receiving placebo), and this difference was maintained over six months (log rank test, P = 0.003). Albendazole had no effect on mortality. Minimal adverse effects were noted. CONCLUSIONS--For HIV infected Zambians with diarrhoea of more than three weeks'' duration albendazole offers substantial relief from symptoms and may be used empirically, without prior investigation.     

Double-blind, placebo-controlled, randomized, pilot clinical trial of ImmunoGuard--a standardized fixed combination of Andrographis paniculata Nees, with Eleutherococcus senticosus Maxim, Schizandra chinensis Bail. and Glycyrrhiza glabra L. extracts in patients with Familial Mediterranean Fever.

Double blind, randomized, placebo controlled pilot study of ImmunoGuard--a standardized fixed combination of Andrographis paniculata Nees., Eleutherococcus senticosus Maxim., Schizandra chinensis Bail., and Glycyrrhiza glabra L. special extracts standardized for the content of Andrographolide (4 mg/tablet), Eleuteroside E, Schisandrins and Glycyrrhizin, was carried out in two parallel groups of patients. The study was conducted in 24 (3-15 years of both genders) patients with Familial Mediterranean Fever (FMF), 14 were treated with tablets of series A (verum) and 10 patients received series B product (placebo). The study medication was taken three times of four tablets daily for 1 month. Daily dose of the andrographolide--48 mg. The primary outcome measures in physician's evaluation were related to duration, frequency and severity of attacks in FMF patients (attacks characteristics score). The patient's self-evaluation was based mainly on symptoms--abdominal, chest pains, temperature, arthritis, myalgia, erysipelas-like erythema. All of 3 features (duration, frequency, severity of attacks) showed significant improvement in the verum group as compared with the placebo. In both clinical and self evaluation the severity of attacks was found to show the most significant improvement in the verum group. Both the clinical and laboratory results of the present phase II (pilot) clinical study suggest that ImmunoGuard is a safe and efficacious herbal drug for the management of patients with FMF.     

Paralytic poliomyelitis in Russian Federation in 1998-2005

From 1998 through 2005 3,294 cases of acute flaccid paralysis (AFP) including 93 cases with clinical picture of poliomyelitis were registered in Russian Federation. From the latter cases 91 were classified as vaccine-associated paralytic poliomyelitis (VAPP): 66 were VAPP cases in oral poliomyelitis vaccine (OPV) recipients and 25--VAPP cases in contacts. VAPP rate was 1 case per 1.6 million of distributed OPV doses, 1 case per 2.2 million doses for OPV recipients, and 1 case per 186,000 doses for recipients of 1st OPV dose in children aged < 1 year. Majority of VAPP cases in recipients occurred after 1st dose (89.4%) and in contacts--in non-vaccinated children (76%). Mean interval between OPV administration and onset of VAPP in recipients was 21 days. Children aged < 1 year were predominant among VAPP cases (92.4% among recipient VAPP cases, and 80% among contact VAPP cases). Majority of the patients had unfavorable health status including defects of immunity. Most of poliovirus strains isolated from VAPP cases belonged to type 3 (52.9%) whereas to type 2 and 1--29.8% and 17.4% of strains respectively. All VAPP cases were associated with vaccine-derived polioviruses. A highly diverged poliovirus type 1 (2.65% of nucleotide substitutions in VP1 region) was isolated from patient with contact VAPP. Formation of poliovirus-neutralizing serum antibodies in children with VAPP including persons with immunodeficiency reflects the ability of the organism to produce specific antiviral immune response.     

Zinc supplementation in children with cholera in Bangladesh: randomised controlled trial

Objective To investigate the impact of zinc supplementation in children with cholera.Design Double blind, randomised, placebo controlled trial.Setting Dhaka Hospital, Bangladesh.Participants 179 children aged 3-14 years with watery diarrhoea and stool dark field examination positive for Vibrio cholerae and confirmed by stool culture.Intervention Children were randomised to receive 30 mg elemental zinc per day (n=90) or placebo (n=89) until recovery. All children received erythromycin suspension orally in a dose of 12.5 mg/kg every six hours for three days.Main outcome measures Duration of diarrhoea and stool output.Results 82 children in each group completed the study. More patients in the zinc group than in the control group recovered by two days (49% v 32%, P=0.032) and by three days (81% v 68%, P=0.03). Zinc supplemented patients had 12% shorter duration of diarrhoea than control patients (64.1 v 72.8 h, P=0.028) and 11% less stool output (1.6 v 1.8 kg/day, P=0.039).Conclusion Zinc supplementation significantly reduced the duration of diarrhoea and stool output in children with cholera. Children with cholera should be supplemented with zinc to reduce its duration and severity.Trial registration Clinical trials {"type":"clinical-trial","attrs":{"text":"NCT00226616","term_id":"NCT00226616"}}NCT00226616.     

Impact of gestrinone on the course of asymptomatic endometriosis.

A new drug, gestrinone, was subjected to the first double blind, randomised placebo controlled trial of any treatment of endometriosis. The disease deteriorated in eight (47%) of the 17 patients prescribed placebo (95% confidence limits 23% and 71%) compared with none of the 18 patients prescribed gestrinone (p = 0.002). There was a difference in elimination of the endometriosis in the gestrinone group compared with placebo but this was not statistically significant (p = 0.057). There was a significant difference in improvement of the disease in the gestrinone group compared with placebo (p = 0.004), confirming that gestrinone is an effective treatment of endometriosis. Endometriosis deteriorates in at least 23% of patients; as it is impossible to predict in whom this will happen, treatment appears to be warranted in all cases.     

Effect of nadolol on plasma lipids in hyperthyroidism

The effect of Nadolol treatment on lipid subfractions in a group of 23 hyperthyroid patients was assessed in a randomised double-blind placebo controlled trial lasting six weeks, carbimazole being given to both groups from weeks 2 to 6. Clinical and biochemical euthyroidism was seen in both groups at 6 weeks; no effect of nadolol on peripheral monodeiodination of T4 to T3 was observed. At time 0 there were significant negative correlations between total cholesterol and free T3 (r = 0.68), and free T4 (r = 0.54). In the Nadolol group there were significant rises between 0 and 6 weeks in total cholesterol (52.6%, P less than 0.01), LDL cholesterol (30.3%, P less than 0.01) and HDL cholesterol (18.2%, P less than 0.05). HDL cholesterol rose significantly in the placebo group (12.4%, P less than 0.05) but there were no significant increases in LDL cholesterol or total cholesterol. The rise in triglyceride during this period in the Nadolol group (64.7%, P less than 0.05) was significantly greater (P less than 0.05) than the rise in the placebo group (8.8%). Nadolol increases triglyceride more than placebo during the early management of hyperthyroidism.     

Comparing the Recurrence of Vulvovaginal Candidiasis in Patients Undergoing Prophylactic Treatment with Probiotic and Placebo During the 6 Months

This is a randomized, double-blind, clinical/comparative trial study, involving the recurrence of vaginal candidiasis (VVC) after initial treatment with oral fluconazole in patients undergoing prophylactic management with a probiotic and placebo for 6 months. Fifty-nine VVC patients who were diagnosed based on their history, physical examination, and culture of vaginal discharge were initially treated by a single dose of 150 mg fluconazole. According to the table of random numbers, the sample was divided into two groups. The patients from one group took probiotics, while those from the other group took a placebo, with all of them being continuously monitored for 6 months. The patients complaining of vaginal candidiasis symptoms, such as burning, pruritus, and a vaginal (curd-like) discharge, were examined and the discharge was cultured for candida. The positive cultures were considered to be recurring for the patients in each group. Thirty-one cases from the placebo group and 28 cases from the probiotic group were carefully observed. In total, the 6-month recurrence in the control group was eleven (35.5 %) and in the research group was two (7.2 %). The results from Fisher’s exact test for the value p = 0.01 and OR 0.14 95 % CI (0.028–0.7) showed significant recurrence in the placebo group. The findings demonstrated that taking probiotics withazole antifungal drugs could be highly effective in treating VVC, resulting in a lower recurrence rate as well.     

低剂量氯吡格雷治疗不稳定型心绞痛的疗效观察

目的:探讨氯吡格雷(泰嘉)治疗不稳定型心绞痛(unstable angina pectoris,UAP)的疗效。方法:102例不稳定型心绞痛患者随机分治疗组(60例)和对照组(42例),治疗组在常规药物的基础上加氯吡格雷50mg,每天1次,连用4周。对照组用常规药物治疗。两组均观察心绞痛的发作次数、24h动态心电图。结果:治疗组显效43例(79.6%),有效5例(9.3%),对照组显效23例(48.0%),有效10例(20.8%),两组相比差异有显著性(p<0.05)。治疗组心绞痛的发作次数与对照组比较明显减少(P<0.01)、24h动态心电图与对照组比较明显改善(P<0.01)。结论:UAP患者在常规药物治疗的基础上联用低剂量氯吡格雷可取得良好效果,且安全性好。     

Selenium in the treatment of autoimmune thyroiditis

We recently conducted a prospective, placebo-controlled clinical study, where we could demonstrate, that a substitution of 200 microg sodium selenite for three months in patients with autoimmune thyroiditis reduced thyroid peroxidase antibody (TPO-Ab) concentrations significantly. Forty-seven patients from the initially 70 patients agreed to participate in a follow-up cross-over study for further six months. One group (n = 13), which initially received selenium continued to take 200 microg sodium selenite (Se-Se), one group stopped taking selenium (Se-0) ( n = 9), another group which received placebo started to take 200 microg selenium (n = 14) (Plac-Se) and the last group was without selenium substitution (Plac-0) (n = 11). TPO-Ab concentrations were measured at beginning and the end of the study. In the Se-Se group, the TPO-Ab concentrations further significantly p = 0.004) decreased from 625 +/- 470 U/ml to 354 +/- 321 U/ml, in the Se-0 group the TPO-Ab concentrations increased significantly p = 0.017) from 450 +/- 335 to 708 +/- 313 U/ml. In the placebo group, the TPO-Ab concentrations in those patients who were followed without selenium substitution were unchanged (1351 +/- 940 vs. 1724 +/- 1112 U/ml, p = 0.555). In contrast, the patients who received 200 microg sodium selenite after placebo, the TPO-Ab concentrations decreased significantly (p = 0.029) from 1182 +/- 723 to 643 +/- 477 U/ml.     

Controlled trial of propranolol to prevent recurrent variceal bleeding in patients with non-cirrhotic portal fibrosis.

Fifty patients with non-cirrhotic portal fibrosis who were admitted to hospital because of upper gastrointestinal bleeding were randomly assigned to treatment with either oral propranolol given in doses that reduced the resting pulse rate by 25% (25 patients) or with a placebo (25 patients). One year after the start of the study 20 patients in the propranolol group and five patients in the placebo group were free from recurrent gastrointestinal bleeding (p less than 0.0001). Giving continuous oral propranolol treatment is therefore effective in preventing recurrent upper gastrointestinal bleeding in patients with non-cirrhotic portal fibrosis.     

Prophylactic co-trimoxazole in biliary surgery.

A double-blind study was conducted to test the prophylactic effect of a single dose of co-trimoxazole on the incidence of septic complications after elective cholecystectomy. Forty-eight patients received co-trimoxazole and 47 placebo. Wound sepsis occurred in 10 (21%) of the controls but in only 2 (4%) of the treated group, and the incidences of pulmonary complications were 49% (23 cases) and 19% (9) respectively. These differences were significnat. Wound sepsis after cholecystectomy occurs mostly in patients with infected bile. Co-trimoxazole given by intravenous infusion rapidly achieves a high concentration in the palsma and is effective against most biliary pathogens.     

经皮微波固化对肝内大血管旁复发性肝癌的疗效及安全性

目的:研究经皮微波固化治疗肝内大血管旁复发性肝癌的疗效和安全性。方法:选择2011年2月~2015年12月在我院进行诊治的不能进行手术切除的肝内大血管(肝静脉、肝后下腔静脉、肝动脉或门静脉)旁复发性肝癌患者80例,随机分为观察组和对照组,观察组进行经皮微波固化治疗,对照组进行手术再切除,于治疗前后检查甲胎蛋白、B超,观察术后并发症的发生情况。结果:观察组治疗后甲胎蛋白转阴16例,降低21例,总有效率为92.5%,明显高于对照组的85.9%(P0.05);治疗后3个月经超声检测肿瘤大小,观察组有15例肿瘤停止生长,21例肿瘤缩小,无效的4例中肿瘤合并肝内转移或出现范围扩大,对照组有14例肿瘤停止生长,19例肿瘤缩小,7例无效,观察组控制肿瘤大小有效率明显大于对照组(P0.05);观察组并发症发生率为22.5%(9/40),明显低于对照组的35.0%(14/40)(P0.05)。结论:经皮微波固化治疗肝静脉、肝后下腔静脉、肝动脉或门静脉旁复发性肝癌疗效确切,术后并发症少,可用于临床肝内大血管旁复发性肝癌患者的治疗。     

Oxpentifylline treatment of venous ulcers of the leg.

OBJECTIVE--To determine the effect of oxpentifylline on the healing of venous ulcers of the leg. DESIGN--Double blind, randomised, prospective, placebo controlled, parallel group study. SETTING--Four outpatient clinics treating leg ulcers in England and the Republic of Ireland. PATIENTS--80 Consecutive patients with clinical evidence of venous ulceration of the leg in whom appreciable arterial disease was excluded by the ratio of ankle to brachial systolic pressure being greater than 0.8. INTERVENTIONS--All patients received either oxpentifylline 400 mg three times a day by mouth or a matching placebo for six months (or until their reference ulcer healed if this occurred sooner) in addition to a locally standardised method of compression bandaging. MAIN OUTCOME MEASURES--The primary end point was complete healing of the reference ulcer within six months. The secondary end point was the change in the area of the ulcer over the six month observation period. RESULTS--Complete healing of the reference ulcer occurred in 23 of the 38 patients treated with oxpentifylline and in 12 of the 42 patients treated with a placebo. Life table analysis showed that the proportion of ulcers healed at six months was 64% in the group treated with oxpentifylline compared with 34% in the group treated with a placebo (log rank test chi 2 = 4.78, p = 0.03), which was significant (odds ratio = 1.81, 95% confidence interval 1.20 to 2.71). CONCLUSION--Oxpentifylline used in conjunction with compression bandaging improves the healing of venous ulcers of the leg.     

The effect of darbepoetin alfa on growth, oxygenation and radioresponsiveness of a breast adenocarcinoma

Tumor hypoxia is associated with poor clinical outcome in a variety of tumors, including cervical, head/neck and breast cancer. Administration of erythropoietic factors has been suggested as a means of improving tumor oxygenation (pO2). This study randomized rats to treatment with low-dose or high-dose darbepoetin alfa or a placebo to determine the effect of darbepoetin alfa on the pO2, growth and response to radiation therapy of R3230 mammary adenocarcinoma. Rats received 3 microg/kg (high dose) or 0.2 microg/kg (low dose) darbepoetin alfa or placebo for eight doses prior to either (1) pO2 measurement and pimonidazole staining or (2) irradiation or sham irradiation on post-transplant day 20. In the animals randomized to radiation treatment, placebo or darbepoetin alfa administration at a reduced dose was continued for 9 weeks or until the tumor diameter exceeded 15 mm (defined as failure for survival analysis). Treatment with high-dose and low-dose darbepoetin alfa produced hematocrits of 68 and 56% compared to 44 and 45% in their respective control groups (both P < 10(-5)). At 18 days post-transplant, tumor volume was not different for either darbepoetin alfa group compared to the placebo group. Tumor oxygenation, as measured by the fraction of pO2 measurement <10 mmHg and the intensity of pimonidazole staining, was significantly improved in the high-dose group (P = 0.046 and 0.03, respectively, compared with controls) but not in the low-dose group. Growth delay curves after irradiation did not differ significantly for high- or low-dose darbepoetin alfa compared to placebo. In this nonanemic animal model of mammary adenocarcinoma, darbepoetin alfa does not significantly alter tumor growth or radioresponsiveness, even though it improves oxygenation when administered at high doses.     

Randomised controlled trial of azathioprine withdrawal in ulcerative colitis.

OBJECTIVE--To determine whether azathioprine can prevent relapse in ulcerative colitis. DESIGN--One year placebo controlled double blind trial of withdrawal or continuation of azathioprine. SETTING--Outpatient clinics of five hospitals. SUBJECTS--79 patients with ulcerative colitis who had been taking azathioprine for six months or more. Patients in full remission for two months or more (67), and patients with chronic low grade or corticosteroid dependent disease (12) were randomised separately. 33 patients in remission received azathioprine and 34 placebo; five patients with chronic stable disease received azathioprine and seven placebo. MAIN OUTCOME MEASURE--Rate of relapse. Relapse was defined as worsening of symptoms or sigmoidoscopic appearance. RESULTS--For the remission group the one year rate of relapse was 36% (12/33) for patients continuing azathioprine and 59% (20/34) for those taking placebo (hazard rate ratio 0.5, 95% confidence interval 0.25 to 1.0). For the subgroup of 54 patients in long term remission (greater than six months before entry to trial) benefit was still evident, with a 31% (8/26) rate of relapse with azathioprine and 61% (17/28) with placebo (p less than 0.01). For the small group of patients with chronic stable colitis (six were corticosteroid dependent and six had low grade symptoms) no benefit was found from continued azathioprine therapy. Adverse events were minimal. CONCLUSIONS--Azathioprine maintenance treatment in ulcerative colitis is beneficial for at least two years if patients have achieved remission while taking the drug. Demonstration of the relapse preventing properties of azathioprine has implications for a large number of patients with troublesome ulcerative colitis, who may benefit from treatment with azathioprine.