Endoscopic,deep mural implantation of Enteryx for the treatment of GERD: 6-month follow-up of a multicenter trial

OBJECTIVES: This prospective, multicenter, single-arm study evaluated the safety and efficacy of the endoscopic implantation of Enteryx, a biocompatible, non-biodegradable liquid polymer for the treatment of GERD. METHODS: Eighty-five patients with heartburn symptoms responsive to proton pump inhibitor (PPI) use were enrolled. Inclusion requirements were HRQL score < or = 11 on PPI and > or = 20 off PPI, and 24-hour PH probe with > or = 5% total time at PH < or = 4. Patients with a hiatus hernia > 3 cm, grade 3 or 4 esophagitis, or esophageal motility disorder were excluded. Using a 4-mm needle tipped catheter during standard endoscopy, implants were made in 3-4 quadrants deep into the wall of the cardia. Use of PPI medications, pH-metry, manometry, GERD symptoms, and patient quality of life were assessed over a 6-month follow-up period. RESULTS: At 6 months, PPI use was eliminated in 74% and reduced by > 50% in 10% of patients. The median HRQL score improved from 24.0 pre-implant (baseline off PPIs) to 4.0 at 6 months (p < 0.001). Mean total esophageal acid exposure time was 9.5% pretherapy and 6.7% at 6 months (p < 0.001). Mean LES length increased from 2.0 cm at baseline to 3.0 cm posttherapy (p = 0.003). There were no clinically serious adverse events. Transient mild-to-moderate chest pain commonly occurred after implantation. CONCLUSIONS: The endoscopic implantation of Enteryx is a safe and effective therapy for eliminating or decreasing the need for PPI medications, improving GERD symptoms and patient quality of life, and decreasing esophageal acid exposure among patients suffering from GERD.     

Endoscopic full-thickness plication for the treatment of GERD: a multicenter trial

BACKGROUND: A novel endoscopic full-thickness plication device has been designed to inhibit gastroesophageal reflux by placing a transmural plication near the gastroesophageal junction under direct endoscopic visualization. This study assessed the safety and efficacy of endoscopic full-thickness plication in the treatment of patients with symptoms caused by GERD. METHODS: Patients with chronic heartburn requiring maintenance therapy with antisecretory medication were recruited. Exclusion criteria were the following: hiatal hernia (>2 cm), grade III and IV esophagitis, and Barrett's esophagus. The following were assessed over a follow-up period of 6 months: GERD-Health-Related Quality of Life, Gastrointestinal Symptom Rating Scale, and SF-36 Health Survey, medication use, 24-hour esophageal pH monitoring and esophageal manometry. Patients underwent a single, full-thickness plication in the gastric cardia just distal to the gastroesophageal junction. Re-treatment was not permitted. RESULTS: A total of 64 patients (mean age 46.3 years, range 23-71 years) underwent endoscopic full-thickness plication (mean procedure time 17.2 minutes). At 6 months after plication, proton pump inhibitor therapy had been eliminated in 74% of previously medication-dependent patients. Median GERD-Health-Related Quality of Life scores improved 67% (19.0 vs. 5.0; p<0.001). Improvements also were observed in median Gastrointestinal Symptom Rating Scale and SF-36 Health Survey mental and physical composite scores. Median esophageal acid exposure improved significantly (10 vs. 8; p<0.008) with normalization of pH noted in 30% of patients. No significant change in esophageal manometry was noted. One gastric perforation occurred and was managed conservatively without sequelae. CONCLUSIONS: In this study, a single full-thickness plication placed at the gastroesophageal junction reduced symptoms, medication use, and esophageal acid exposure associated with GERD.     

Transoral, flexible endoscopic suturing for treatment of GERD: a multicenter trial

BACKGROUND: A totally transoral outpatient procedure for the treatment of GERD would be appealing. METHODS: A multicenter trial was initiated that included 64 patients with GERD treated with an endoscopic suturing device. Inclusion criteria were 3 or more heartburn episodes per week while not taking medication, dependency on antisecretory medicine, and documented acid reflux by pH monitoring. Exclusion criteria were dysphagia, grade 3 or 4 esophagitis, obesity, and hiatus hernia greater than 2 cm in length. Patients underwent manometry, endoscopy, 24-hour pH monitoring, and symptom severity scoring before and after the procedure. Patients were randomized to a linear or circumferential plication configuration. Adverse procedural events were recorded. RESULTS: Mean 6-month symptom score changes demonstrated procedural efficacy. Heartburn severity and frequency as well as regurgitation all improved (p > 0.0001 for each). Twenty-four-hour pH monitoring showed improvement in number of episodes below pH of 4 at 3 and 6 months (p < 0.0007 and 0.0002) and percentage of total time the pH was less than 4 at 6 months (p < 0.011). Plication configuration did not affect symptoms or pH monitoring results. One patient had a self-contained suture perforation that was successfully treated with antibiotics. CONCLUSION: Endoscopic gastroplasty is safe. It is associated with reduced symptoms and medication use at 6 month follow-up in patients with uncomplicated GERD.     

Endoluminal gastroplasty (EndoCinch) versus endoscopic polymer implantation (Enteryx) for treatment of gastroesophageal reflux disease: 6-month results of a prospective, randomized trial

OBJECTIVES: The aim of this study was to compare and determine the efficiency and safety of two newly introduced endoscopic antireflux procedures in the treatment of gastroesophageal reflux disease (GERD). METHODS: In a prospective, randomized trial, endoluminal gastroplasty (EndoCinch) was compared with polymer injection (Enteryx) employing 51 consecutive patients dependent on proton pump inhibitor therapy. Follow-up evaluation included drug consumption, symptoms, quality-of-life scoring, endoscopy, pH monitoring, manometry, and documentation of adverse events. RESULTS: Twenty-six patients were assigned to EndoCinch treatment, 23 patients received Enteryx implantation, and two patients dropped out before applying endoscopic therapy. At 6 months, proton pump inhibitor therapy could be stopped or dosage was reduced by > or =50% in 20 of 26 (77%) EndoCinch-treated patients and in 20 of 23 patients treated by Enteryx (87%, p= 0.365), which differed significantly in both groups compared to the pre-interventional status (p < 0.0001). Esophageal acid reflux (pH < 4) decreased from 14.5% to 9.6% in EndoCinch-treated patients (p= 0.071) and from 15.5% to 13.9% in patients treated by Enteryx (p= 0.930). Heartburn symptom score, modified DeMeester score, gastrointestinal life quality index, and SF-36 physical health survey score improved significantly in both groups postinterventionally (p < 0.0001). Approximately 25% of the patients in both groups required retreatment in an attempt to achieve symptom control. CONCLUSIONS: This is the first prospective, randomized study directly comparing two endoscopic anti-GERD techniques. EndoCinch and Enteryx seem to be equally successful in the treatment of GERD significantly reducing the proton pump inhibitor dosages, and also by improving symptoms of patients. Both endoluminal antireflux procedures may be promising therapeutic options; long-term evaluation will have to show if the positive initial results can be maintained.     

Controlled trial of 6-month and 8-month regimens in the treatment of pulmonary tuberculosis: The results up to 24 months

Four short-course antituberculosis regimens allocated at random were studied; (1) streptomycin, isoniazid and rifampicin given daily for 6 months; (2) these 3 drugs plus pyrazinamide given daily for 2 months, followed by twice-weekly streptomycin, isoniazid and pyrazinamide; (3) a regimen which differed from regimen 2 only in that ethambutol replaced pyrazinamide, and (4) streptomycin, isoniazid, rifampicin and pyrazinamide given 3 times a week for 4 months, followed by streptomycin, isoniazid and pyrazinamide twice a week. The last 3 regimens were given for 6 or 8 months by random allocation.All except 1 of 680 patients with drug-sensitive tubercle bacilli pretreatment had a favourable bacteriological response during chemotherapy. The relapse rates during the period from the end of chemotherapy up to 24 months in the non-ethambutol series were 6–7% following the 6-month regimens and 1–3% following the 8-month regimens. However in the ethambutol series, 23 % of 84 patients had a bacteriological relapse after 6 months of chemotherapy, and 10 % of 84 after 8 months. All except 1 of the patients with strains initially resistant to either isoniazid or streptomycin had a favourable bacteriological response during chemotherapy. Of the patients with strains resistant to both drugs, all those in the ethambutol series had a favourable bacteriological response during chemotherapy, but the results were not so good in the other series. Relapse after the end of chemotherapy among patients with initially resistant strains was commonest in the ethambutol series; it was not associated with the emergence of further drug resistance in any of the series.     

Dihydroergokryptine vs. placebo in dementia of Alzheimer type: interim results of a randomized multicenter study after a 1-year follow-up

In order to evaluate the efficacy of dihydroergokryptine mesylate (DEK) - a semisynthetic ergot alkaloid having a neuroprotective activity through the activation of antioxidant enzymatic systems - in dementia of Alzheimer type, a long-term, randomized, placebo-controlled, double-blind study was carried out. The interim analysis after 1-year follow-up is here reported. Two-hundred-and-fifteen patients fulfilling the NINCDS-ADRDA criteria for probable Alzheimer's disease were enrolled by 14 geriatric and neurologic Italian centers. The study design included a 1-month pre-treatment phase with placebo; 1-year double-blind treatment with DEK or placebo; a further 1-year open phase of treatment with DEK. The active drug dosage was 5 mg bid orally administered for the first 2 weeks, 10 mg bid for the following 2 weeks, 20 mg bid for the following 11 months. Efficacy was assessed by means of Gottfries-Br?ne-Steen (GBS) Rating Scale for dementia and Mental Deterioration Battery. The univariate analysis showed a significant improvement of GBS subscales and factors (with the exception of the Factor III, depression-anxiety). Multivariate analysis showed a significant difference between treatments in GBS scale (P=0.002) without any influence of age and illness duration. These results were confirmed by the end-point analysis carried out on GBS scores using baseline value as covariate. Minor adverse events were observed in 9 out of 108 patients (8.3%) of the DEK group and in 7 out of 107 (6.5%) of the placebo group. No change in blood pressure, heart rate and routine laboratory tests was observed. These preliminary results suggest positive symptomatic effects of DEK on elderly patients with probable Alzheimer's disease indicating a slowing down of the cognitive decline.     

Nonresorbable copolymer implantation for gastroesophageal reflux disease: a randomized sham-controlled multicenter trial

BACKGROUND & AIMS: This aim was to determine whether endoscopic implantation of a biocompatible nonresorbable copolymer (Enteryx; Boston Scientific Corp, Natick, MA) is a more effective therapy for gastroesophageal reflux disease (GERD) than a sham procedure. METHODS: In a randomized, single-blind, prospective, multicenter clinical trial, 64 patients with GERD were enrolled whose symptoms were well controlled by proton pump inhibitor (PPI) therapy and rapidly recurred after cessation of PPI therapy. Thirty-two patients were assigned to Enteryx implantation and 32 to a sham procedure consisting of standard upper endoscopy. Patients in both groups with unsatisfactory symptom relief after 3 months were eligible for re-treatment by Enteryx implantation. The primary study end point was > or =50% reduction in PPI use. Secondary end points included > or =50% improvement in GERD score and the proportion of patients not undergoing re-treatment procedure. Follow-up evaluations were performed at 3 and 6 months. RESULTS: The percentage of Enteryx-treated patients achieving a > or =50% reduction in PPI use (81%) was greater than that of the sham group (53%), with a rate ratio of 1.52 (confidence interval [CI], 1.06-2.28; P=.023). A higher proportion of the Enteryx (68%) than sham group (41%) ceased PPI use completely (rate ratio, 1.67; CI, 1.03-2.80; P=.033). GERD health-related quality of life heartburn score improvement > or =50% was achieved by 67% of the Enteryx group versus 22% of the sham group (rate ratio, 3.05; CI, 1.55-6.33; P <.001). More Enteryx-treated (81%) than sham-treated (19%) patients did not undergo re-treatment (rate ratio, 4.33; CI, 2.23-9.29; P <.001). CONCLUSIONS: Enteryx implantation more effectively reduces PPI dependency and alleviates GERD symptoms than a sham procedure.     

Policies for interim analysis and interim reporting of results

The key ethical issues involved in developing policies for interim reports and interim analyses are considered. Then the twin topics of the appropriate contents of interim reports and the components of an appropriate interim analysis are discussed. Finally, suggested policies are offered.     

Flecainide versus quinidine: results of a multicenter trial

In this multicenter trial, the efficacy and safety of flecainide, a new antiarrhythmic agent, were compared with those of quinidine, a standard antiarrhythmic agent in the United States. A randomized, parallel, placebo-controlled design was used. Flecainide was more effective than quinidine (p less than 0.0001) in reducing ventricular premature complexes, couplets and ventricular tachycardia. Flecainide continued to be effective in reducing ventricular arrhythmias during a 12-month follow-up period. The incidence of side effects was similar for the 2 drugs in both short- and long-term studies. Therefore, flecainide should be an excellent drug to use in treating patients with ventricular arrhythmias classified as either benign or potentially malignant.     

Short-term and long-term outcome of endoluminal gastroplication for the treatment of GERD: the first multicenter trial in Japan

Purpose  Endoluminal gastroplication (ELGP) was the first endoscopic therapy for gastroesophageal reflux disease (GERD). Data on the long-term outcomes, including the plication status and data from Asian populations, are limited. The aim of this study was to evaluate the short-term and long-term effectiveness and safety of ELGP for GERD in the Japanese population. Methods  This was an open-label, prospective, multicenter trial of ELGP. Forty-eight patients with GERD were enrolled. The procedure involved placing circumferential plications 1–2 cm below the GE junction using the EndoCinch system. Outcome measurements were improvement of heartburn, medication use, endoscopic Los Angeles grade, durability of plications, 24-h esophageal acid exposure, esophageal manometry, and frequency of adverse events. Results  During the 24-month follow-up, the rate of complete resolution of heartburn ranged from 54 to 66%, the rate of discontinuation or reduction of PPI/H₂RA use ranged from 65 to 76%, and the rate of endoscopic classification to grade O ranged from 66 to 81%. The status with more than one plication remaining was associated with higher rates of improvement of heartburn, PPI/H₂RA use, and endoscopic findings as compared with those associated with the loss of all plications. A modest decrease of the esophageal acid exposure level, but no change of the manometric parameters, was observed after ELGP. No serious adverse events were observed. Conclusions  In this 24-month follow-up study conducted in Japanese subjects, ELGP was found to be effective in about 60% of patients with GERD, and the procedure was safe.     

Endoscopic full-thickness plication for the treatment of GERD: 12-month follow-up for the North American open-label trial

BACKGROUND: The aim of this study was to assess the intermediate-term (12-month) safety and efficacy of endoscopic full-thickness plication in patients with symptomatic GERD. METHODS: Sixty-four patients with chronic heartburn that required maintenance antisecretory therapy received a single, endoscopically placed, full-thickness plication in the gastric cardia 1 cm distal to the gastroesophageal junction. At baseline and 12 months after plication, patients completed the GERD Health Related Quality of Life questionnaire, Gastrointestinal Symptom Rating Scale, and SF-36 Health Survey, as well as a medication use diary. Ambulatory 24-hour pH monitoring and esophageal manometry were obtained at baseline and 3 months after plication. At 6 months after plication, the 24-hour pH study was repeated. RESULTS: Of the 57 patients who completed the 12-month follow-up, 40 (70%) were no longer taking a proton pump inhibitor. Median GERD Health Related Quality of Life scores were improved compared with baseline while taking medication (19.0 vs. 5.0; p < 0.0001) and while not taking medication (13.0 vs. 5.0; p < 0.002). At 6 months after the procedure, an improvement in distal esophageal acid exposure was demonstrated in 40 of 51 patients (80%), with a decrease of 39% in the median percentage of time the pH was less than 4 (p < 0.0001). Normal pH scores were observed in 30% of patients. All procedure-related adverse events occurred acutely, as previously reported, and no new adverse event was observed during extended follow-up. CONCLUSIONS: Full-thickness plication at the gastroesophageal junction is an effective endoscopic procedure for treatment of patients with symptoms caused by GERD. It reduces reflux symptoms and antisecretory medication use over at least a 1-year period.     

Long-term efficacy and safety of etanercept in children with polyarticular-course juvenile rheumatoid arthritis: interim results from an ongoing multicenter,open-label,extended-treatment trial

OBJECTIVE: To evaluate the long-term efficacy and safety of etanercept in children with juvenile rheumatoid arthritis (JRA) participating in an ongoing multicenter, open-label, extended-treatment trial. All patients had been participants in an initial randomized efficacy and safety trial of etanercept. METHODS: Etanercept was administered at a dosage of 0.4 mg/kg (maximum 25 mg) subcutaneously twice each week. Safety and efficacy evaluations were performed every 3-4 months. The JRA 30% definition of improvement (DOI) was defined as improvement of > or =30% in at least 3 of 6 response variables used to assess disease activity, with no more than 1 variable worsening by more than 30%. RESULTS: At the time of analysis, 48 of the 58 patients (83%) were still enrolled in the study; 43 of them (74%) had completed 2 years of treatment. Of these 43 patients, 81% met the JRA 30% DOI, 79% met the JRA 50% DOI, and 67% met the JRA 70% DOI. Ten children started low-dose methotrexate after year 1. Of the 32 children taking prednisone, the dosage was decreased to <5 mg/day in 26 (81%). Two children had serious infections (varicella with aseptic meningitis in one and complicated sepsis in the other). In general, adverse events were of the types seen in a general pediatric patient population. CONCLUSION: Children with severe, longstanding, methotrexate-resistant polyarticular JRA demonstrated sustained clinical improvement with >2 years of continuous etanercept treatment. Etanercept was generally well-tolerated. There were no increases in the rates of adverse events over time. However, children taking etanercept should be monitored closely for infections.     

Rikkunshito improves symptoms in PPI-refractory GERD patients: a prospective, randomized, multicenter trial in Japan

Background

To seek a promising therapeutic regimen for proton pump inhibitor (PPI)-refractory patients with gastroesophageal reflux disease (GERD) after the standard PPI treatment, we compared the efficacies of rikkunshito (a Japanese traditional medication) combined with rabeprazole (RPZ) and a double dose of RPZ in a prospective randomized multicenter trial in Japanese PPI-refractory GERD patients.

Methods

One hundred and four patients with GERD symptoms remaining after 4-week treatment with RPZ (10?mg/day) were randomly assigned to 4?weeks of either combination therapy [rikkunshito (7.5?g/day) with a standard dose of RPZ (10?mg/day)] or a double dose of RPZ (20?mg/day). The primary endpoint was the improvement rate, calculated based on the frequency scale for the symptoms of GERD (FSSG) before and after treatment. Subgroup analysis was also performed with respect to each subject??s background factors such as reflux esophagitis (RE)/non-erosive GERD (NERD), age, gender, and body mass index (BMI).

Results

Four-week treatment with rikkunshito combined with RPZ significantly decreased the FSSG score from 17.6?±?6.5 to 12.0?±?6.9, similar to the decrease seen on treatment with a double dose of RPZ. Regarding the therapeutic improvement rate, there were also significant effects in both groups. However, in the subgroup analysis based on RE/NERD, the improvement rate of male NERD patients in the rikkunshito group was significantly greater than that of such patients in the other group (P?P?Conclusion Rikkunshito combined with standard-dose RPZ therapy may be a useful new strategy for PPI-refractory GERD patients.     

Administration of cyclosporine for 24 months compared with 6 months for prevention of chronic graft-versus-host disease: a prospective randomized clinical trial.

This study compared the incidence of clinical extensive chronic graft-versus-host disease (GVHD), transplantation-related mortality, survival, and relapse-free survival among recipients randomly assigned to receive a 24-month or a 6-month course of cyclosporine prophylaxis after transplantation of allogeneic marrow from an HLA-identical sibling or alternative donor. Patients who did not have clinical manifestations of chronic GVHD on day 80 after transplantation were eligible for the study if they previously had acute GVHD or if a skin biopsy showed histologic evidence of chronic GVHD. Clinical extensive chronic GVHD developed in 35 of the 89 patients (39%) in the 24-month group and 37 of the 73 patients (51%) in the 6-month group. The hazard of developing chronic GVHD was not significantly different in the 2 groups (hazard ratio = 0.76; 95% confidence interval, 0.48-1.21; P =.25). In addition, there were no significant differences between the 2 groups in transplantation-related mortality, survival, or disease-free survival.