A clinical trial of rosiglitazone and 5-aminosalicylate combination for ulcerative colitis

Objective To investigate the therapeutic effects of the combination of rosiglitazone, which is peroxisome proliferators-activated receptorγ(PPARγ) ligands used to treat type 2 diabetes mellitus, and aminosalicylate on mildly or moderately active ulcerative colitis and on relevant cytokine expressions. Methods According to the     

α-Blockade and thiazide treatment of hypertension A double-blind randomized trial comparing doxazosin and hydrochlorothiazide

This trial involved 107 patients in a two-group, parallel, double-blind, randomized study comparing the diuretic, hydrochlorothiazide (HCTZ) (dose 25 to 50 mg) and the α₁ antagonists, doxazosin (dose 2 to 16 mg). All randomized participants were followed for at least 1 year. Participants were recruited from the community. The study was carried out in four phases: Phase I—Baseline; Phase II—Monotherapy Titration; Phase III—Combination Therapy Titration; and Phase IV—Maintenance. The following measures were carried out: blood pressure, biochemistries, lipids/lipoproteins, quality of life, ambulatory electrocardiograms, echocardiograms, adverse experiences, and drug adherence. Both drugs were well tolerated, with only 4% taken off doxazosin and 7% off HCTZ. Adverse experiences were uncommon and mostly mild. Both drugs were effective in managing hypertension over 1 year of therapy. There was no difference noted in terms of efficacy of blood pressure lowering between the two study drugs, nor was there any evidence of tolerance developing or of any serious adverse effects.Average final doses for drugs were 7.8 mg for doxazosin and 36 mg for HCTZ. The results show that, over the course of 1 year, both drugs significantly lowered systolic and diastolic pressures compared to baseline; doxazosin (−19 and −16 mm Hg); HCTZ (−22 and 15 mm Hg). Blood pressure lowering was not significantly different between drugs. Sitting heart rate was not affected by drugs. Changes in quality of life measures were similar between groups. Echocardiographic measures at 1 year showed significant between-drug differences in change in left internal end systolic and diastolic dimensions and end systolic stress. Both doxazosin and HCTZ were effective drugs over 1 year for treating hypertension.     

Does home treatment affect delirium? A randomised controlled trial of rehabilitation of elderly and care at home or usual treatment (The REACH-OUT trial)

BACKGROUND: delirium is a frequent adverse consequence of hospitalisation for older patients, but there has been little research into its prevention. A recent study of Hospital in the Home (admission substitution) noted less delirium in the home-treated group. SETTING: a tertiary referral teaching hospital in Sydney, Australia. METHODS: we randomised 104 consecutive patients referred for geriatric rehabilitation to be treated in one of two ways, either in Hospital in the Home (early discharge) or in hospital, in a rehabilitation ward. We compared the occurrence of delirium measured by the confusion assessment method. Secondary outcome measures were length of stay, hospital bed days, cost of acute care and rehabilitation, functional independence measure (FIM), Mini-Mental State Examination (MMSE) and geriatric depression score (GDS) assessed on discharge and at 1- and 6-month follow-up and patient satisfaction. RESULTS: the home group had lower odds of developing delirium during rehabilitation [odds ratio (OR) = 0.17; 95% confidence interval 0.03-0.65], shorter duration of rehabilitation (15.97 versus 23.09 days; P = 0.0164) and used less hospital bed days (20.31 versus 40.09, P < or = 0.0001). The cost was lower for the acute plus rehabilitation phases (7,680 pounds versus 10,598 pounds; P = 0.0109) and the rehabilitation phase alone (2,523 pounds versus 6,100 pounds; P < or = 0.0001). There was no difference in FIM, MMSE or GDS scores. the home group was more satisfied (P = 0.0057). CONCLUSIONS: home rehabilitation for frail elderly after acute hospitalisation is a viable option for selected patients and is associated with a lower risk of delirium, greater patient satisfaction, lower cost and more efficient hospital bed use.     

Origin of and therapeutic approach to cardiac syndrome X： Results of the proton pump inhibitor therapy for angina-like lingering pain trial （PITFALL trial）

AIM： To investigate the frequency of gastroenterological diseases in the etiology and the efficacy of proton pump inhibitors （PPIs） in the treatment of cardiac syndrome X （CSX） as a subform of non-cardiac chest pain （NCCP）. METHODS： We investigated 114 patients with CSX using symptom questionnaires. A subgroup of these patients were investigated regarding upper gastrointestinal disorders （GIs） and treated with PPI. Patients not willing to participate in investigation and treatment served as control group. RESULTS： Thirty-six patients denied any residual symptoms and were not further evaluated. After informed consent in 27 of the remaining 78 patients, we determined the prevalence of disorders of the upper GI tract and quantified the effect of treatment with pantoprazole. We found a high prevalence of gastroenterological pathologies （26/27 patients, 97%）with gastritis, gastroesophageal reflux disease （GERD） and acid reflux as the most common associated disorders. If treated according to the study protocol, these patients showed a significant improvement in the symptom score. Patients treated by primary care physicians, not according to the study protocol had a minor response to treatment （n = 19, -43%）, while patients not treated at all （n = 26） had no improvement of symptoms （-0%）. CONCLUSION： Disorders of the upper GI tract are a frequent origin of CSX in a German population and can be treated with pantoprazole if given for a longer period.     

Phase II trial of biochemotherapy with interferon α, dacarbazine, cisplatin and tamoxifen in metastatic melanoma: a Southwest Oncology Group trial

The therapeutic benefit of adding interferon α (IFNα) to established single-agent and combination chemotherapy regimens for the treatment of metastatic melanoma has not been proven. We designed the present study to estimate the response rate of IFNα, dacarbazine, cisplatin and tamoxifen in patients who had not been treated with systemic therapy for advanced disease. Using a schedule similar to that which had previously been shown to favor IFNα plus dacarbazine over dacarbazine alone, we treated patients with an “induction” regimen of IFNα, 15 mU m⁻² day⁻¹ intravenously 5 days/week for 3 weeks. Following induction, schedules of IFNα, 5 mU m⁻² day⁻¹ subcutaneously three times a week, and tamoxifen, 10 mg orally twice a day, were begun. Dacarbazine, 250 mg m⁻² day⁻¹ and cisplatin 33 mg m⁻² day⁻¹ for 3 consecutive days were repeated every 4 weeks, and subcutaneous IFNα and oral tamoxifen were continued until the discontinuation of chemotherapy. We treated 25 patients (18 men and 7 women, median age 52 years) and observed only 1 objective response (response rate 4%, 95% confidence interval 0.1%–20%). The toxicities of the regimen consisted of moderate myelosuppression and constitutional side-effects. On the basis of the low antitumor activity of this regimen, we do not recommend it for further study or for use as standard therapy of metastatic melanoma. Received: 11 August 1998 / Accepted: 21 December 1998     

Long acting octreotide in the treatment of advanced hepatocellular cancer and overexpression of somatostatin receptors： Randomized placebo-controlled trial

AIM: To estimate if and to what extent long acting octreotide (LAR) improves survival and quality of life in patients with advanced hepatocellular carcinoma (HCC). METHODS: A total of 127 cirrhotics, stages A-B, due to chronic viral infections and with advanced HCC, were enrolled in the study. Scintigraphy with 111Indium labeled octreotide was performed in all cases. The patients with increased accumulation of radionuclear compound were randomized to receive either oral placebo only or octreotide/octreotide LAR only as follows: octreotide 0.5mg s.c. every 8 h for 6 wk, at the end of wk 4-8 octreotide LAR 20 mg i.m. and at the end of wk 12 and every 4 wk octreotide LAR 30mg i.m.. Follow-up was worked out monthly as well as the estimation of quality of life (QLQ-C30 questionnaire). Patients with negative somatostatin receptors (SSTR) detection were followed up in the same manner. RESULTS: Scintigraphy demonstrated SSTR in 61 patients. Thirty were randomized to receive only placebo and 31 only octreotide. A significantly higher survival time was observed for the octreotide group (49 ± 6 wk) as compared to the control group (28 ± 1 wk) and to the SSTR negative group (28 ± 2 wk), LR = 20.39, df = 2, P < 0.01. The octreotide group presented 68.5% lower hazard ratio [95% CI (47.4%-81.2%)]. During the f irst year, a 22%, 39% and 43% decrease in the QLQ-C30 score was observed in each group respectively.CONCLUSION: The proposed therapeutic approach has shown to improve the survival and quality of life in SSTR positive patients with advanced HCC.     

Efficacy and safety of mizoribine for the treatment of Sjögren's syndrome: a multicenter open-label clinical trial

Abstract

This multicenter clinical trial was performed to evaluate the efficacy and safety of mizoribine for the treatment of Sjögren's syndrome. Fifty-nine patients with a definite diagnosis of Sjögren's syndrome received 150^Smg of mizoribine daily for 16 weeks. The salivary secretion volume was determined at baseline, at weeks 8 and 16 after the start of the study treatment by the Saxon test, and clinical manifestations were assessed by the investigator and the patients using a 10-cm visual analog scale (VAS). Adverse drug reactions were reported in 18 patients, of whom 6 patients had to discontinue the study due to such adverse reactions; however, no serious adverse drug reactions definitely related to the study drug were noted. The salivary secretion volume, the rate of change in salivary secretion, the patients’ own assessments of dry mouth and dry eyes, the investigators’ assessment of oral sicca symptoms, and the investigators’ overall assessment improved following the treatment regimen with statistical significance at week 16 after the start of treatment in comparison to the baseline values. These results suggested that mizoribine may be effective in producing a subjective and objective amelioration of the glandular symptoms in patients with Sjögren's syndrome, without observing any serious adverse effects related to this drug.     

Efficacy and safety of mizoribine for the treatment of Sjögren's syndrome: a multicenter open-label clinical trial

This multicenter clinical trial was performed to evaluate the efficacy and safety of mizoribine for the treatment of Sjögren's syndrome. Fifty-nine patients with a definite diagnosis of Sjögren's syndrome received 150^Smg of mizoribine daily for 16 weeks. The salivary secretion volume was determined at baseline, at weeks 8 and 16 after the start of the study treatment by the Saxon test, and clinical manifestations were assessed by the investigator and the patients using a 10-cm visual analog scale (VAS). Adverse drug reactions were reported in 18 patients, of whom 6 patients had to discontinue the study due to such adverse reactions; however, no serious adverse drug reactions definitely related to the study drug were noted. The salivary secretion volume, the rate of change in salivary secretion, the patients’ own assessments of dry mouth and dry eyes, the investigators’ assessment of oral sicca symptoms, and the investigators’ overall assessment improved following the treatment regimen with statistical significance at week 16 after the start of treatment in comparison to the baseline values. These results suggested that mizoribine may be effective in producing a subjective and objective amelioration of the glandular symptoms in patients with Sjögren's syndrome, without observing any serious adverse effects related to this drug.     

Randomized clinical trial: efficacy and safety of telbivudine and lamivudine in treatment-naïve patients with HBV-related decompensated cirrhosis

Summary. Patients with decompensated cirrhosis owing to chronic hepatitis B viral (HBV) infection have a high morbidity/mortality rate, and the treatment remains a challenge. We studied the safety and efficacy of telbivudine and lamivudine in such patients. This noninferiority, double‐blind trial randomized 232 treatment‐naive patients with decompensated HBV (1:1) in 80 academic hospitals to receive once‐daily telbivudine 600 mg or lamivudine 100 mg for 104 weeks. Primary composite endpoint was proportion of patients with HBV DNA <10 000 copies/mL, normal alanine aminotransferase (ALT) and Child‐Turcotte‐Pugh score improvement/stabilization at week 52. Response rates using a post hoc modified endpoint (HBV DNA <300 copies/mL [57 IU/mL] and ALT normalization) in intent‐to‐treat analysis (missing = failure) were 56.3%vs 38.0% after 76 weeks (P = 0.018) and 45.6%vs 32.9% after 104 weeks (P = 0.093) for telbivudine vs lamivudine. Telbivudine treatment was an independent predictive factor for HBV DNA <300 copies/mL and ALT normalization (P = 0.037). Response rates with protocol‐defined composite endpoint in intent‐to‐treat analysis (M = F) were 56.2 vs 54.0% (noninferiority not achieved) and 39.1%vs 36.4% (noninferiority achieved) in telbivudine and lamivudine groups at 52 and 104 weeks. Telbivudine treatment was associated with a significant improvement in glomerular filtration rate compared to lamivudine treatment and was also associated with a trend for improvement in survival (87%vs 79%). No cases of lactic acidosis were reported. Telbivudine compared to lamivudine was associated with a higher rate of patients with both viral suppression and ALT normalization, a trend towards a higher rate of survival and significant improvement in glomerular filtration.     

Safety and efficacy of infliximab therapy in active behcet’s uveitis: an open-label trial

In this open-label trial, ten male patients with active Behcet’s uveitis were enrolled. Initially, two infliximab infusions (5 mg/kg) were given at weeks 0 and 2. The patients continued to receive conventional therapy on recurrence of severe uveitis (RSU) attack. The patients with further attack were regularly given infliximab infusions every 8 weeks. In cases of further RSU attacks, the infusion interval was reduced to 6 weeks. The total follow-up period was 3 years. The patients were monitored for RSU, visual acuity and adverse effects. Reduction in the doses of prednisolone was also monitored. After receiving two infliximab infusions at weeks 0 and 2, three patients remained attack-free and seven patients had another RSU attack between 8th and 47th week. These patients were regularly given infliximab at 8-week intervals. Five out of seven patients remained attack-free. In two patients who had further attack, infusion frequency was increased to 6 weeks. There was a remarkable improvement in visual acuity with no significant adverse reaction except mild respiratory tract infection (two patients), headache (one patient) and mild infusion reaction (one patient). Infliximab is a safe and effective drug for the management of Behcet’s uveitis. Selection of optimal dose and frequency of infusion required standardization for individual patient.     

Randomized controlled trial of steroid withdrawal followed by continuous and intermittent administration of natural α-interferon for chronic hepatitis B

Forty-two chronic hepatitis B patients positive for hepatitis B e antigen were randomly assigned to either intermittent or continuous administration of natural α-interferon after steroid withdrawal. The effects of the treatment were judged by their HBeAg/HBeAb serostatus and biochemical response. Temporary responses of HB e seronegative rates of these two protocols were 25.0% and 31.8%, and those of the HB e seroconversion rates were 15.0% and 13.6%, respectively. No significant difference was detected between the two treatment protocols. Biochemical response was seen in nine (40.9%) and eight (40.0%) cases out of 22 intermittent and 20 continuous cases, respectively. No significant difference was seen between the two groups. The patients' characteristics were examined for their relation to the sequelae of HB e antigen and biochemical responses. Younger age was a favorable condition for HB e antigen disappearance, although it was not statistically significant (P = 0.0791). The shorter interval between the cessation of steroid treatment and the beginning of interferon administration was a significantly favorable factor on biochemical response.     

Do all services provided as part of a clinical trial require research ethics and governance review?

Appropriate ethical oversight underpins the conduct of all clinical trials in Australia. In addition, clinical trials require a suitable approach to research governance in order to ensure that research is appropriately governed. However, such governance processes are often onerous and time‐consuming and are not required when trial practices are more appropriately understood as standard of care clinical services.