Complete Resolution Of Heartburn Research Articles

Efficacy and safety of tegoprazan in the treatment of gastroesophageal reflux disease: A protocol for meta-analysis and systematic review.

The incidence of gastroesophageal reflux disease (GERD) is increasing year by year, the clinical manifestations are complex and diverse, and the adverse effects of long-term use of proton pump inhibitors and gastrointestinal motility drugs have been of great concern in recent years. The effectiveness of tegoprazan in the treatment of GERD is still controversial. This protocol describes a systematic review and meta-analysis to evaluate the efficacy and safety of tegoprazan in the treatment of gastroesophageal reflux disease. PubMed, Embase, Cochrane Library and Web of Science will be searched from the database inception to 1 March 2023. All randomized controlled trials related to tegoprazan for GERD will be included. Extracted data will include publication details, basic information, demographic data, intervention details and patient outcomes. The primary outcome will be complete resolution of major symptoms, complete resolution of heartburn, proportion of heartburn-free days, chronic cough, hoarseness, and adverse events. Risk of bias will be assessed using the Cochrane Collaboration's tool for assessing risk of bias. Article selection, data extraction and risk of bias assessment will be performed in duplicate by two independent reviewers. If the meta-analysis is precluded, we will conduct a descriptive synthesis using a best-evidence synthesis approach. The results of this study will provide reliable evidence to evaluate the efficacy and safety of tegoprazan in the treatment of GERD and help patients, physicians and clinical investigators choose the most appropriate treatment.

Efficacy of esophagus protection in complex treatment of erosive gastroesophageal reflux disease: a systematic review and meta-analysis of controlled trials

To review the data about the efficacy of esophagus protective agent based on the fixed combination of hyaluronic acid and chondroitin sulfate dissolved in the bioadhesive carrier (poloxamer 407) in the complex therapy of patients with erosive gastroesophageal reflux disease (GERD). A search in MEDLINE/PubMed, EMBASE, Cochrane, and Russian Science Citation Index of Scientific Electronic Library electronic databases was performed. Relevant original controlled studies of a fixed combination of hyaluronic acid and chondroitin sulfate as an esophagus protective agent in a population of patients with erosive GERD were included. The final analysis included three studies that enrolled 181 patients with erosive GERD. All the studies had a uniform design with the assessment of the primary endpoints (complete epithelialization of esophageal erosions and complete resolution of heartburn) 28 days after the start of therapy. Meta-analysis of the three controlled trials has demonstrated that combination therapy with proton pump inhibitors (PPIs) and esophagus protective agents is significantly more effective than PPI monotherapy for complete epithelialization of esophageal erosions at 28 days of treatment (relative risk 1.267, 95% confidence interval 1.082-1.483, p=0.003; I2=21.19%), but did not differ for complete resolution of heartburn on the day 28 of treatment (relative risk 1.638, 95% confidence interval 0.660-4.067, p=0.287; I2=92.59%). Combined therapy with PPI and Alfasoxx is significantly more effective than PPI monotherapy for the epithelialization of esophageal erosions in patients with erosive GERD.

The outcome of fundoplication in patients with GERD based on abnormal impedance testing.

The role of impedance testing in selecting patients for antireflux surgery is poorly understood. The aim of this study was to compare the outcomes of patients that underwent antireflux surgery for GERD based on an abnormal pH/abnormal impedance test versus a normal pH/abnormal impedance test. Records of patients who had an abnormal off-medication impedance test (≥ 48 total reflux events) who underwent antireflux surgery were reviewed and divided into two groups: normal [pH-] or abnormal [pH+] esophageal acid exposure (DeMeester score > 14.7). Symptom resolution was compared: scale 1 (no resolution) to 5 (complete resolution). Eighty-two patients met criteria: 44 [pH+] and 38 [pH-]. There were no differences in the demographics or indications for surgery. The frequencies of heartburn and regurgitation symptoms were significantly reduced by fundoplication in both groups. Complete resolution of heartburn was more common in the [pH+] group (90%) compared to the [pH-] group (67%) [p = 0.02]. Resolution of regurgitation was similar in both groups (90% in the [pH+] group vs 79% in the [pH-] group, p = 0.20). The mean dysphagia frequency score decreased for the [pH+] group, but increased in the [pH-] group. New-onset dysphagia was more common in [pH-] patients (23%) compared to [pH+] patients (5%), (p = 0.02). Continued use of PPI medications was significantly more likely in [pH-] group (42%) compared to the [pH+] group (21%). There was no difference in surgical satisfaction rates between groups. Patients with abnormal impedance and increased esophageal acid exposure had significantly better symptom resolution, less dysphagia, and less frequent PPI use with antireflux surgery versus those with normal pH. These findings urge caution in the use of abnormal impedance values with normal esophageal acid exposure for the selection of patients for an antireflux operation.

Analysis of 2-Week Data from Two Randomized, Controlled Trials Conducted in Subjects with Frequent Heartburn Treated with Esomeprazole 20 mg

PurposeThese secondary analyses used data from 2 similarly designed studies in subjects experiencing frequent heartburn to evaluate the efficacy of esomeprazole 20 mg once daily for 2 weeks, which reflects the approved over-the-counter dosage and duration. MethodsSubjects without endoscopically identified erosive esophagitis who were experiencing heartburn for ≥6 months and ≥4 of 7 days prior to baseline (study 1, N = 368; study 2, N = 349) were randomly assigned to receive double-blind treatment with esomeprazole 40 or 20 mg (administered as esomeprazole magnesium trihydrate 44.5 and 22.3 mg, respectively) or placebo once daily for 4 weeks. Subjects recorded the severity of heartburn in a daily diary, and investigators assessed subjects at each study visit. Two-week assessments were the primary end points of interest in these analyses and included the percentage of subjects with complete heartburn resolution (no episodes during 7 consecutive days), time to sustained complete heartburn resolution (the first of 7 consecutive episode-free days), and heartburn relief (no episodes other than ≤1 mild episode during 7 consecutive days). FindingsAt week 2, the percentages of subjects who experienced complete heartburn resolution were significantly greater with esomeprazole 40 mg (study 1, 26.1%; study 2, 35.3%) and 20 mg (study 1, 25.2%; study 2, 35.7%) compared with placebo (study 1, 9.0%; study 2, 3.4%) (all, P ≤ 0.001). Beginning on day 1, the percentages of subjects who experienced sustained heartburn resolution was significantly greater in the groups treated with esomeprazole 40 mg (study 1, 19%; study 2, 19%; P < 0.0001) and 20 mg (study 1, 10%; study 2, 15%; P < 0.05) compared with the group that received placebo (study 1, 2%; study 2, 1%). Additionally, at week 2, the percentages of subjects experiencing heartburn relief were significantly greater with esomeprazole 40 mg (study 1, 35.3%; study 2, 40.5%) and 20 mg (study 1, 34.5%; study 2, 46.4%) compared with placebo (study 1, 16.5%; study 2, 8.6%) (all, P ≤ 0.001). ImplicationsThe results of this study demonstrate that once-daily treatment with esomeprazole 20 mg for 2 weeks effectively resolved subjects׳ heartburn compared with placebo, beginning on day 1. Studies precede FDA Act 801 clinical trial registration and results submission requirements.

Identifying Clinical Predictors of Heartburn Resolution With Over-the-Counter Esomeprazole

Introduction: Identifying factors associated with complete resolution of heartburn (HB) during treatment may help set appropriate expectations for the use of over-the-counter (OTC) proton-pump inhibitor therapy for frequent HB. These analyses were conducted to determine patient-level factors related to HB resolution during treatment with esomeprazole (ESO) at the approved OTC dose/duration. Methods: Data were pooled from the first 14 days in subjects with frequent HB randomly assigned to double-blind treatment with ESO 20 mg (n=921; administered as 22.3 mg esomeprazole magnesium trihydrate) or placebo (n=909) in 6 similarly designed studies conducted at US study centers. Subjects recorded HB episodes in daily diaries throughout the 14-day treatment period. Multivariate analyses were conducted to identify predictors of complete HB resolution, defined as no 24-hour HB for 7 consecutive days. The following clinical predictors were assessed using a stepwise logistic regression adjusted for study: treatment, study site, age (as a continuous variable), gender, race, pre-treatment HB frequency, and the occurrence of HB during treatment. Additional analyses explored alternate endpoints, including complete resolution of daytime and nighttime HB episodes for 7 consecutive days, and other predictive variables only available in subsets of the overall data set. Pre-treatment HB frequency was primarily ≥2 days/week; mean age was 45.5 years (range: 18-90 years). Results: Treatment with ESO (p < .0001), age (p=.0006), nighttime HB during treatment (p < .0001), and lower pre-treatment HB frequency (p < .0001) were significant predictors of complete resolution of 24-hour HB. Significant predictors of complete resolution of daytime HB (4 studies) were treatment with ESO, age, nighttime HB during treatment, and lower pre-treatment daytime HB frequency (p < .0001 for all). Treatment with ESO, age, frequency of pre-treatment nighttime HB, and daytime HB during treatment were predictors of complete resolution of nighttime HB (p < .0001 for all). Conclusion: Patient factors associated with complete resolution of HB with ESO 20 mg included increasing age, absence of nighttime HB during treatment, and less-frequent pre-treatment HB.

Comparative study of Omeprazole, Rabeprazole and Ilaprazole for their efficacy in patient suffering from reflux esophagitis with symptoms.

AIM- To evaluate whether there is any difference in efficacy between three proton pump inhibitors, Omeprazole, Rabeprazole and Ilaprazole in patients of reflux esophagitis with symptoms METHODS- The study was a prospective , randomized open label comparison, total one hundred and four patients with erosive reflux esophagitis in which 32 patients(group-A) received 20mg Omeprazole, 35 patients (group-B)received 20mg Rabeprazole, 37 patients (group-C) received 10mg Ilaprazole once a day in the morning. Daily change in heart burn and acid reflux symptoms in the first 7 days of administration were assessed using a four-point scale (0: none; 1: mild; 2: moderate; 3: severe). Rate of endoscopic healing of reflux esophagitis at week 8 were also assessed between three groups. RESULTS- All the groups were well matched in terms of age, sex, H pylori status, and the proportion of cases with heart burn and acid reflux symptoms before the administration of drugs. The mean heart burn scores in patients treated with Ilaprazole more rapidly decreased than those receiving Omeprazole or Rabeprazole. Complete resolution of heart burn was also more rapid in patient treated with Ilaprazole for 5 days compared with patients taking other proton pump inhibitors. Again acid reflux scores more rapidly decreased with Ilaprazole but no significant difference were seen between groups. Rate of endoscopic healing of reflux esophagitis was also more in Ilaprazole

Editor’s Briefing

<b>Background:</b> Adequacy of acid suppression is a critical factor influencing healing in gastro-oesophageal reflux disease (GORD). The European prospective study ProGORD was set up to determine the endoscopic and symptomatic progression of GORD over five years under routine care, after initial acid suppression with esomeprazole. We report on factors influencing endoscopic healing and symptom resolution during the acute treatment phase. <b>Methods:</b> Patients with symptoms suggestive of GORD underwent endoscopy and biopsies were obtained from the oesophagus for diagnosis of abnormalities, including Barrett’s oesophagus (BO). Data from 6215 patients were included in the “intention to treat” analysis, 3245 diagnosed as having erosive reflux disease (ERD) and 2970 non-erosive reflux disease (NERD). ERD patients were treated with esomeprazole 40 mg for 4–8 weeks for endoscopic healing while NERD patients received 20 mg for 2–4 weeks for resolution of heartburn symptoms. <b>Results:</b> Endoscopic healing occurred overall in 87.7% of ERD patients although healing was significantly lower in those with more severe oesophagitis (76.9%) and in those with BO (72.4%), particularly in <i>Helicobacter pylori</i> negative BO patients (70.1%). Age, sex, and body mass index appeared to have no significant impact on healing. Complete heartburn resolution was reported by 70.4% of ERD patients and by 64.8% of NERD patients at the last visit. Only <i>H pylori</i> infection had a significant influence on complete heartburn resolution in the NERD group (68.1% and 63.7% for <i>H pylori</i> positive and <i>H pylori</i> negative, respectively; p = 0.03). <b>Conclusion:</b> The presence of Barrett’s mucosa, as well as severe mucosal damage, exerts a negative impact on healing. <i>H pylori</i> infection had a positive influence on healing in ERD patients with coexistent BO but no influence on those without BO.

Efficacy of adding sodium alginate to omeprazole in patients with nonerosive reflux disease: a randomized clinical trial

Nonerosive reflux disease (NERD) is the most common form of gastroesophageal reflux disease. Patients with NERD have a lower response rate to proton pump inhibitors (PPIs) than patients with erosive esophagitis when gauged from relief of heartburn. Sodium alginate decreases the acidity of refluxate and protects the esophageal mucosa. However, whether the addition of sodium alginate to PPI therapy can improve NERD symptoms remains unknown. Accordingly, the aim of this study was to evaluate the efficacy of adding sodium alginate to basal PPI therapy for NERD. Patients who had experienced heartburn on at least 2 days per week during the 1-month period before entering the study and had no endoscopic mucosal breaks (grade M or N according to Hoshihara's modification of the Los Angeles classification) were randomized to one of two treatments for 4 weeks: omeprazole (20 mg once daily) plus sodium alginate (30 mL four times a day) (group A) or omeprazole (20 mg once daily) alone (group B). Eighty-seven patients were enrolled, and 76 patients were randomly assigned to group A (n = 36) or group B (n = 40). Complete resolution of heartburn for at least 7 consecutive days by the end of treatment was significantly more common in group A (56.7%) than in group B (25.7%). One patient from group A had mild drug-related diarrhea that was not clinically serious. In conclusion, omeprazole combined with sodium alginate was better than omeprazole alone in Japanese patients with NERD.

Arbaclofen Placarbil in GERD: A Randomized, Double-Blind, Placebo-Controlled Study

It has been shown that arbaclofen placarbil (AP) inhibits reflux in gastroesophageal reflux disease (GERD) following single oral dosing. This study evaluated the efficacy and safety of AP over 4 weeks in subjects with symptomatic GERD. One hundred fifty-six subjects with heartburn and/or regurgitation ≥3 days/week and either no history of taking proton pump inhibitors (PPIs naive, n=58) or at least partial symptom response to PPI therapy (PPI responsive, n=98) were enrolled in this randomized, double-blind, placebo-controlled trial. All GERD therapies including PPIs were discontinued 2 weeks before randomization to AP 20, 40, or 60 mg daily, 30 mg twice daily, or placebo for 4 weeks. Randomization was stratified by prior PPI use. In the primary analysis, change from baseline in weekly heartburn events between AP and placebo for the entire study group was not statistically significant. However, a significant interaction was observed between prior PPI use and response to AP treatment. In pre-planned secondary analyses of the PPI-responsive subgroup, percent reductions from baseline in weekly heartburn events were greater for each AP dose vs. placebo (P<0.05) and the percentage of subjects who reported complete resolution of heartburn during week 4 was higher in each AP treatment group (21, 28, 30, and 50% for AP 20, 40, 60 mg daily, and 30 mg twice daily, respectively) compared with placebo (6%) (P<0.05 for 30 mg twice daily). Corresponding analyses of the PPI-naive subgroup showed no significant differences. AP was well tolerated; withdrawals due to adverse events were infrequent. AP was not superior to placebo in reducing the number of weekly heartburn events over 4 weeks in the primary analysis of the entire study population. Exploratory subgroup analyses suggest that response to PPI treatment before the study was associated with a response to AP treatment.

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

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. 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. 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. 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.

Clinical trial: the treatment of gastro‐oesophageal reflux disease in primary care – prospective randomized comparison of rabeprazole 20 mg with esomeprazole 20 and 40 mg

A trial of empirical PPI therapy is usual practice for most patients with symptoms of gastro-oesophageal reflux disease (GERD) in primary care. To determine if the 4-week efficacy of rabeprazole 20 mg for resolving heartburn and regurgitation symptoms is non-inferior to esomeprazole 40 mg or 20 mg. In all, 1392 patients were randomized to rabeprazole 20 mg, esomeprazole 20 mg or 40 mg once daily. Patients, doctors and assessors were blinded. Symptom resolution data were collected on days 0-7 and day-28 using the Patient Assessment of Upper Gastrointestinal Disorders Symptom Severity Index with a shortened version used on days 8-27. Rabeprazole 20 mg was non-inferior to esomeprazole 40 mg for complete resolution of regurgitation and satisfactory resolution of heartburn and regurgitation. For complete heartburn resolution, the efficacy of rabeprazole 20 mg and esomeprazole 40 mg was statistically indistinguishable, although the non-inferiority test was inconclusive. Rabeprazole 20 mg was non-inferior to esomeprazole 20 mg for all outcomes. In uninvestigated GERD patients, rabeprazole 20 mg was non-inferior to esomeprazole 40 mg for complete and satisfactory relief of regurgitation and satisfactory relief of heartburn, and not different for complete resolution of heartburn.

Long-term symptomatic outcomes after Collis gastroplasty with fundoplication

Collis gastroplasty with fundoplication is an accepted treatment for gastroesophageal reflux disease (GERD) complicated by short esophagus. The procedure can be done either via left thoracotomy or using minimally invasive laparoscopic techniques. Few centers have reported long-term follow-up for patients undergoing a Collis gastroplasty using both the open and minimal access techniques. Retrospective review of prospectively collected data at Creighton University was done to identify patients who underwent Collis gastroplasty with fundoplication for GERD. After approval from the institutional review board, the patients were contacted and administered a questionnaire regarding symptoms and satisfaction. Data were entered in a dataset and analyzed from the patient's perspective. Eighty-five patients underwent a Collis gastroplasty procedure over a period of 13 years. Forty-eight percent (41 cases) were performed laparoscopically, and a transthoracic open repair was performed in the rest. Long-term data (more than 9 months) was available on 52 patients. Surgery resulted in complete resolution of heartburn, chest pain, regurgitation, and dysphagia in 52, 22, 54, and 29% of patients, respectively. More than 75% of the patients were satisfied with the outcome of surgery, and more than 85% would recommend the procedure to another patient. Collis gastroplasty with fundoplication results in good long-term patient satisfaction and symptom control.

Comparative study of omeprazole, lansoprazole, pantoprazole and esomeprazole for symptom relief in patients with reflux esophagitis

To clarify whether there is any difference in the symptom relief in patients with reflux esophagitis following the administration of four Proton pump inhibitors (PPIs). Two hundred and seventy-four patients with erosive reflux esophagitis were randomized to receive 8 wk of 20 mg omeprazole (n = 68), 30 mg of lansoprazole (n = 69), 40 mg of pantoprazole (n = 69), 40 mg of esomeprazole (n = 68) once a day in the morning. Daily changes in heartburn and acid reflux symptoms in the first 7 d of administration were assessed using a six-point scale (0: none; 1: mild; 2: mild-moderate; 3: moderate; 4: moderate-severe; 5: severe). The mean heartburn score in patients treated with esomeprazole more rapidly decreased than those receiving other PPI. Complete resolution of heartburn was also more rapid in patients treated with esomeprazole for 5 d compared with omeprazole (P = 0.0018, P = 0.0098, P = 0.0027, P = 0.0137, P = 0.0069, respectively), lansoprazole (P = 0.0020, P = 0.0046, P = 0.0037, P = 0.0016, P = 0.0076, respectively), and pantoprazole (P = 0.0006, P = 0.0005, P = 0.0009, P = 0.0031, P = 0.0119, respectively). There were no significant differences between the four groups in the rate of endoscopic healing of reflux esophagitis at week 8. Esomeprazole may be more effective than omeprazole, lansoprazole, and pantoprazole for the rapid relief of heartburn symptoms and acid reflux symptoms in patients with reflux esophagitis.

Efficacy and safety of omeprazole in Japanese patients with nonerosive reflux disease

There is increasing awareness of nonerosive reflux disease (NERD) as a disease requiring treatment in Japan. This randomized, double-blind, placebo-controlled, parallel-group study was conducted to investigate the efficacy and safety of omeprazole 10 mg and 20 mg once daily in Japanese patients with NERD. Patients with heartburn for at least 2 days a week during the month before entry into the study and no endoscopic signs of a mucosal break (grade M or N according to Hoshihara's modification of the Los Angeles classification) were randomly assigned to one of three groups (omeprazole 10 mg or 20 mg, or placebo) once daily for 4 weeks. Overall, 355 patients were enrolled, of whom 284 were randomly assigned to one of the three groups (omeprazole 10 mg, n = 96; omeprazole 20 mg, n = 93; placebo, n = 95). The rate of complete resolution of heartburn in week 4 was significantly higher in patients treated with omeprazole 10 mg [32.3%, 95% confidence interval (CI), 22.9%-41.6%] or 20 mg (25.8%, 95% CI, 16.9%-34.7%) than in the placebo group (12.0%, 95% CI, 5.3%-18.6%). No significant difference between the two omeprazole groups was observed. The rate of complete resolution of heartburn by omeprazole was similar between patients with grade M and those with grade N esophagus. Omeprazole also increased the rate of sufficient relief from heartburn. Omeprazole was well tolerated. Omeprazole 10 mg or 20 mg once daily is effective and well tolerated in patients with NERD regardless of their endoscopic classification.

Predictors of treatment response in patients with non‐erosive reflux disease

Up to 40% of patients with non-erosive reflux disease (NERD) fail to respond to proton pump inhibitor therapy. To determine useful prognostic factors for response to and suppression in NERD. A pooled analysis from three multicentre, double-blind trials of patients with a normal endoscopy and heartburn for 4 days or more during the 7 days prior to the start of each treatment. Patients received omeprazole 20 mg, esomeprazole 20 mg or esomeprazole 40 mg/day for 4 weeks. Complete resolution of heartburn was defined as no heartburn during the last week. Of 2458 patients included, complete heartburn resolution was achieved in 63% at the end of 4 weeks treatment. Response on days 5-7 provided an 85% probability of complete resolution of heartburn at 4 weeks; the probability of complete heartburn resolution at 4 weeks in those with moderate to severe symptoms on days 5-7 was 22%. Sensitivity and specificity of no heartburn on days 5-7 was 55% and 83% respectively. Patient demographics, duration of symptoms, medications used, other symptoms and body mass index were not predictors. Assessment of heartburn resolution during the first week of therapy was the best predictor of treatment success at 4 weeks in non-erosive reflux disease, but was suboptimal as a test.

INTRAVENOUS PROTON PUMP INHIBITOR (PPI) THERAPY AND EARLY HEARTBURN SYMPTOM RELIEF IN PATIENTS WITH GERD

Purpose: There are limited data on heartburn symptom relief during first 4 h of therapy with acid-inhibiting drugs. This study investigated symptom relief over this period in subjects receiving i.v. omeprazole, which rapidly increases pH to >6 in fasting subjects, after a provocative meal. Methods: A single-centre, double-blind, randomized, 2-way cross-over study was conducted. Patients with macroscopically abnormal esophageal mucosa were excluded. At first visit, eligible patients (n = 75) were given a provocative meal (hamburger and fries, coca cola, coffee and mint chocolates); those developing at least moderate heartburn within 3 h were given placebo as i.v. bolus followed by continuous infusion for 4 h. To exclude placebo responders, those who experienced complete sustained symptom relief within 30 min were withdrawn. After 7-day washout, those remaining were randomized to receive either active treatment or placebo, and given a provocative meal (visit 2). At first perception of heartburn, patients received either omeprazole 80 mg or placebo (30 min bolus) followed by i.v. infusion of omeprazole 8 mg/h or placebo for 3.5 h. Patients graded symptoms according to Treatment Satisfaction Scale (TSQ), a 5-point Likert scale, every 15 minutes for 4 h. At visit 3, following 7-day washout the intervention was repeated. Adverse events were reported at follow-up, within 2–9 days of visit 3. Results: Thirty eight patients were randomized to placebo/omeprazole and 37 to omeprazole/placebo. Of these, 32 and 35, respectively were included in a per protocol analysis. Mean severity of heartburn during the 4-h treatment period was significantly lower (P <0.001) with omeprazole (2.5; 95% CI 2.3, 2.7) than placebo (2.7, 95% CI, 2.5, 2.9). However, over the 4-h period, no statistically significant differences were observed between omeprazole and placebo, with respect to maximum severity, sustained relief or complete resolution of heartburn. The i.v. omeprazole dose regimen was well-tolerated. Few adverse events were reported, and none were considered serious by the investigator. Conclusions: In a 4-h period after a provocative meal, i.v. omeprazole reduced the severity of meal-induced heartburn. However, overall differences observed between the two treatments were small, and their clinical relevance uncertain.

Effectiveness of proton pump inhibitors in nonerosive reflux disease

Background & Aims: Little information is available about the efficacy of proton pump inhibitors (PPIs) in patients with nonerosive reflux disease (NERD). We aimed to synthesize available data and determine the effectiveness of PPIs on symptom resolution in patients with NERD. Methods: A systematic review of the literature identified studies reporting the effects of PPIs in patients with NERD. Heartburn resolution data were pooled across studies. The effectiveness of PPI therapy in inducing complete heartburn resolution was compared in patients with NERD vs. erosive esophagitis (EE). Results: Seven trials evaluating heartburn resolution in NERD were identified. Higher proportions of patients reported achieving sufficient heartburn resolution compared with complete heartburn resolution. The effect of PPIs on sufficient heartburn resolution was observed sooner than was complete heartburn resolution. Therapeutic gain of PPI therapy over placebo ranged from 30% to 35% for sufficient heartburn control and from 25% to 30% for complete heartburn control. Pooled response rates at 4 weeks were significantly higher for patients with EE compared with NERD (56% vs. 37%, P < 0.0001). Conclusions: PPIs provide a more modest therapeutic gain in patients with NERD as compared with those with EE. A trend in increased therapeutic gain for NERD patients was shown throughout the 4 weeks, suggesting that 4 weeks of follow-up evaluation may be insufficient to show full therapeutic gain in this patient population.

Health-related quality of life improves with treatment-related GERD symptom resolution after adjusting for baseline severity

Severity and frequency of gastroesophageal reflux disease (GERD) related symptoms are associated with impaired health-related quality of life (HRQL). This study evaluated the association between baseline heartburn severity and endpoint HRQL of patients treated for heartburn and the relationship between complete resolution of heartburn symptoms and HRQL outcomes after controlling for baseline severity. We completed a secondary analysis of clinical symptom and HRQL data from three clinical trials in adult patients receiving either omeprazole or ranitidine treatment for GERD. HRQL was assessed using the Psychological General Well-Being Index (PGWB) in each of the three clinical trials, and two of the trials also included the Medical Outcomes Study Sleep disturbance scale. Gastrointestinal symptoms were evaluated using either the Gastrointestinal Symptom Rating Scale or a modified version of the scale. Baseline heartburn severity (none/minor, mild, moderate or severe) was defined based on patient-reported symptoms. Analysis of covariance (ANCOVA) models were used to compare mean HRQL scores by baseline level of heartburn symptom severity and whether or not patients experienced complete heartburn resolution. At baseline, PGWB scores were significantly worse (p < 0.05) for patients with more severe heartburn symptoms. There were no statistically significant baseline severity by symptom resolution interactions in any of the ANCOVA models. For all three trials and across all follow-up assessments, mean PGWB scores were statistically significantly higher for patients with completely resolved heartburn symptoms versus those whose symptoms were unresolved (all p-values < 0.05). Few significant effects were observed for sleep disturbance scores. While the severity of heartburn symptoms at the start of medical treatment for GERD is not associated with improvements in HRQL in subsequent weeks of treatment, complete resolution of symptoms is associated with improvements in psychological well-being.

High- versus standard-dose ranitidine for control of heartburn in poorly responsive acid reflux disease: a prospective, controlled trial

Objective: H 2-receptor antagonists are commonly used as initial therapy in patients with gastroesophageal reflux disease (GERD) and are frequently continued at the same or higher doses when symptoms persist after 4–6 wk of therapy. Our objective was to compare the efficacy of twice-daily treatment with either ranitidine 150 mg b.i.d. or 300 mg b.i.d. in resolving heartburn in GERD patients who remained symptomatic after 6 wk of therapy with ranitidine 150 mg b.i.d. Methods: This was a two-phase, prospective study. In the first phase, GERD patients with heartburn on ≥ 4 of the 7 days before entry were treated with open-label ranitidine 150 mg b.i.d. for 6 wk. In the second phase, patients who were still symptomatic were randomized to 8 wk of double-blind ranitidine therapy at either the same (150 mg b.i.d.) or a higher dose (300 mg b.i.d.). The primary efficacy variable was the resolution of heartburn at wk 4 and 8, as monitored through diary cards. Results: Of the 481 patients treated for 6 wk in phase I, 285 (59%) were still symptomatic; 271 patients (95% of those still symptomatic) were randomized to double-blind treatment with ranitidine. In phase II, 45% of the patients in each treatment group experienced no more than mild heartburn; complete heartburn resolution was observed in < 20% of patients in either group at wk 4 and 8. There were no significant differences in efficacy between the two treatment groups. Conclusions: These results indicate that the majority of GERD patients still have symptoms of heartburn after 6 wk of ranitidine therapy. Only a minority of these patients experience complete relief of heartburn after an additional 8 wk of treatment, which demonstrates that doubling the dose of ranitidine is not efficacious.

Laparoscopic Nissen fundoplication for gastroesophageal reflux disease

This is a retrospective review from March 1994 through October 1996 of 78 patients who underwent laparoscopic Nissen fundoplication for gastroesophageal reflux disease (GERD). The purpose of this study was to evaluate the postoperative results and complications. The patient profile included 38 men and 40 women with a mean age of 46 years (range 11 to 81). The main preoperative symptoms included heartburn (92%), respiratory problems (42%), and dysphagia (32%). Preoperative assessment included esophagogastroduodenoscopy, upper gastrointestinal series, esophageal manometry, and 24-hour pH monitoring. Essential indications for surgery included esophagitis (83%), Barrett's esophagus without dysplasia (22%), and esophageal stricture (23%). All patients underwent a 360-degree wrap with a Maloney dilator and division of the short gastric vessels. The mean operative time was 206 minutes (range 90 to 455). The average time for patients to tolerate a full liquid diet was 1.2 days, and the mean hospital stay was 2.4 days. Current follow-up, from 3 to 36 months, showed complete resolution of heartburn without medications in 67 patients (86%), occasional heartburn in 8 patients (10%), and slight improvement of heartburn in 3 patients (4%). Five patients with preoperative Barrett's metaplasia showed no evidence of it postoperatively (n = 2) or marked regression (n = 3). Laparoscopic Nissen fundoplication is the procedure of choice for patients with complicated GERD.