4-week Healing Rate Research Articles

Efficacy and safety of tegoprazan for duodenal ulcers in Chinese patients: a multicenter, randomized, double-blind, non-inferiority, phase III study

Objective Tegoprazan represents a newly developed potassium-competitive acid blocker utilized for the treatment of acid-related disorders. The present study aimed to explore the therapeutic effectiveness of tegoprazan in Chinese individuals with duodenal ulcers (DU). Methods In the current multicenter, randomized, double-blind, double-dummy, parallel-group, non-inferiority, phase III clinical trial, individuals with DU underwent randomization 1:1 to be administered tegoprazan 50 mg or lansoprazole 30 mg once daily. The primary efficacy endpoint was the 6-week cumulative endoscopic ulcer healing rate. Secondary endpoints included 4-week endoscopic ulcer healing rate and relief of DU-related gastrointestinal symptoms at weeks 2, 4, and 6. Safety analysis encompassed adverse events (AEs) and laboratory indexes. Results The 6-week cumulative endoscopic ulcer healing rates were 96.9% (188/194) and 99.0% (189/191) in the tegoprazan and lansoprazole groups, respectively, indicating a difference of −2.0% (95% confidence interval (CI) = −4.9 to 0.8) in the full analysis set (FAS). The corresponding healing rates were 98.4% (185/188) and 99.5% (183/184) in the per-protocol set, respectively, indicating a difference of −1.1% (95% CI = −3.1 to 1.0). The 4-week healing rates in the tegoprazan and lansoprazole groups were 89.2% (173/194) and 88.5% (169/191) in the FAS, respectively, with a difference of 0.7% (95% CI = −5.6 to 7.0). Treatment-related AEs, all mild-to-moderate, were reported in 38.2% (78/204) and 48.2% (94/195) of participants in the tegoprazan and lansoprazole groups, respectively. Conclusions Tegoprazan 50 mg once daily is effective and non-inferior to lansoprazole 30 mg once daily in Chinese patients with DU, showing a promising safety and tolerability profile. ClinicalTrials.gov registration number NCT05010954.

Potassium-competitive acid blockers and proton-pump inhibitors for healing of erosive esophagitis: a systematic review and network meta-analysis.

Proton-pump inhibitors (PPIs) and potassium-competitive acid blockers (P-CABs) are recommended for erosive esophagitis (EE), with good safety and tolerance. However, it is unclear which is the best treatment option for EE. This study aimed to evaluate the comparative efficacy of P-CABs and PPIs for healing EE patients, seeking an appropriate treatment choice in the 4- or 8-week treatment and standard or double dose. A systematic review and network meta-analysis. Relevant databases were searched to collect randomized controlled trials of PPIs and P-CABs in the treatment of EE up to 31 May 2023. Studies on standard or double-dose PPIs or P-CABs which were published in English and assessed 4- or 8-week healing effects in EE were included. A network meta-analysis was performed to evaluate the efficacy of the treatments under the frequentist framework. Sensitivity and subgroup analyses of patients with different baseline EE were also conducted. In all, 34 studies involving 25,054 patients and 9 PPIs, 6 P-CABs, or placebo treatment interventions were included. The pooled 4-week healing rate was significantly statistically lower than the pooled 8-week healing rate for most treatments. Besides, the higher healing rate of double-dose treatment than standard-dose treatment was not observed in the initial treatment of most drugs. The main analysis only included studies conducted for both patients with and without severe EE at baseline, and the proportion of severe EE included in the study was >10%, Keverprazan 20 mg qd ranked best with a surface under the cumulative ranking curve (SUCRA) value of 84.7, followed by Ilaprazole 10 mg qd with a SUCRA value of 82.0, for the healing rate at 8 weeks. Sensitivity analysis showed that the results were robust. Subgroup analysis showed that most P-CABs had higher healing rates than PPIs, particularly for patients with severe EE. And the healing rate of Keverprazan 20 mg qd at 8 weeks ranked best in the subgroup without or with severe EE at baseline. This study showed that an 8-week treatment seemed more effective than the 4-week treatment for healing EE patients. The healing effect of Keverprazan (20 mg qd) ranked best in 8-week treatment, for both severe and non-severe EE patients. The study protocol was registered with INPLASY (registration number INPLASY2023120053).

Effect and safety of anaprazole in the treatment of duodenal ulcers: a randomized, rabeprazole-controlled, phase III non-inferiority study.

The pharmacokinetic and clinical behaviors of many proton pump inhibitors (PPIs) in peptic ulcer treatment are altered by CYP2C19 genetic polymorphisms. This non-inferiority study evaluated the efficacy and safety of the novel PPI anaprazole compared with rabeprazole. We also explored the influence of Helicobacter pylori (H. pylori) infection status and CYP2C19 polymorphism on anaprazole. In this multicenter, randomized, double-blind, double-dummy, positive-drug parallel-controlled, phase III study, Chinese patients with duodenal ulcers were randomized 1:1 to receive rabeprazole 10 mg + anaprazole placebo or rabeprazole placebo + anaprazole 20 mg once daily for 4 weeks. The primary efficacy endpoint was the 4-week ulcer healing rate assessed by blinded independent review. Secondary endpoints were the proportion of patients with improved overall and individual duodenal ulcer symptoms at 4 weeks. Furthermore, exploratory subgroup analysis of the primary endpoint by H. pylori status and CYP2C19 polymorphism was conducted. Adverse events were monitored for safety. Non-inferiority analysis was conducted for the primary endpoint. The study enrolled 448 patients (anaprazole, n = 225; rabeprazole, n = 223). The 4-week healing rates were 90.9% and 93.7% for anaprazole and rabeprazole, respectively (difference, -2.8% [95% confidence interval, -7.7%, 2.2%]), demonstrating non-inferiority of anaprazole to rabeprazole. Overall duodenal ulcer symptoms improved in 90.9% and 92.5% of patients, respectively. Improvement rates of individual symptoms were similar between the groups. Healing rates did not significantly differ by H. pylori status or CYP2C19 genotype for either treatment group. The incidence of treatment-emergent adverse events was similar for anaprazole (72/220, 32.7%) and rabeprazole (84/219, 38.4%). The efficacy of anaprazole is non-inferior to that of rabeprazole in Chinese patients with duodenal ulcers. ClinicalTrials.gov, NCT04215653.

Vonoprazan versus lansoprazole in the treatment of artificial gastric ulcers after endoscopic submucossal dissection: a randomized, open-label trial

BackgroundVonoprazan is more potent and longer acting than traditional proton pump inhibitor. Although vonoprazan is expected to be superior to proton pump inhibitor, its efficacy in the treatment of gastric ulcers following endoscopic submucosal dissection (ESD) is not fully understood. The aim of this study was to evaluate the effectiveness of vonoprazan in artificial ulcer healing following ESD.MethodsPatients with gastric tumors were randomly assigned to the vonoprazan group (group V) or lansoprazole group (group L) after ESD. Patients received intravenous lansoprazole (30 mg) twice on the day of ESD. Thereafter, patients were treated with vonoprazan (20 mg/day) in group V or lansoprazole (30 mg/day) in group L. Esophagogastroduodenoscopy was performed 4 and 8 weeks after the ESD.ResultsA total of 168 patients were analyzed. The 4-week healing rate for artificial ulcer was not significantly higher in group V versus group L (17/85, 20.0% vs. 14/83, 16.9%, respectively). In addition, there were no significant differences between the 4-week shrinkage rates between the two groups. Postoperative bleeding occurred in none of the patients in group V and three in group L. One patient in group V presented delayed perforation 2 days after ESD.ConclusionsVonoprazan might not be superior to lansoprazole in the healing of artificial gastric ulcer after ESD.Trial registration: University hospital Medical Information Network (registration number: UMIN000016642), Registered 27 February 2015, https://www.umin.ac.jp/ctr/index-j.htm.

Three-dimensional digital imaging is as accurate and reliable to measure leg ulcer area as transparent tracing with digital planimetry.

An accurate and reliable method for measuring venous leg ulcer (VLU) area is important in assessing treatment effects. The new three-dimensional (3D) LifeViz digital imaging system (QuantifiCare S.A., Valbonne, France) combines a compact, easy to use stereovision camera and image management software to provide 3D medical images. The aim of this prospective study was to investigate whether the 3D LifeViz digital imaging system could be considered a suitable alternative to manual transparent wound tracing for the measurement of VLU area and 4-week healing rates. A prospective cohort study was conducted in two tertiary centers between November 2013 and January 2014. The intrarater variability of the digital imaging system was assessed by comparison of the target wound (TW) areas obtained at the inclusion visit (W0) and 2days after W0 for each local rater. The inter-rater variability of the two methods at W0 and the study end visit was assessed using the TW area measurements obtained by local and central raters. A total of 36 consecutive outpatients, each presenting with at least one VLU and representing a total of 44 TWs, were recruited. At inclusion, comparable results were observed with both methods in terms of mean VLU area, showing a good correlation of the digital imaging method with the transparent tracing method (concordance correlation coefficient [CCC], 0.989; 95% confidence interval [C], 0.983-0.992). Furthermore, this system detected the same changes in the 4-week healing rate as the transparent tracing method, showing that both methods were equivalent in measuring changes in VLU areas over time (CCC, 0.996; 95% CI, 0.994-0.997). Strong intrarater and inter-rater concordances demonstrated good reproducibility of the digital imaging system for VLU area measurements (CCC, 0.994 [95% CI, 0.992-0.995] for intrarater variability; and CCC ≥0.99 for each center for inter-rater variability). Moreover, regardless of the operator measuring the VLUs, the reliability of image capture and image quality remained excellent. The 3D LifeViz digital imaging system is a noncontact stereophotographic method that provides measurements of VLU area or changes in VLU areas that are as accurate and reliable as those obtained using the planimetry method and in conditions as close as possible to those of a clinical trial.

Efficacy of proton pump inhibitors for patients with duodenal ulcers: A pairwise and network meta-analysis of randomized controlled trials

Background/Aim:To compare the efficacy and tolerance of different proton pump inhibitors (PPIs) in different doses for patients with duodenal ulcers.Materials and Methods:An electronic database was searched to collect all randomized clinical trials (RCTs), and a pairwise and network meta-analysis were performed.Results:A total of 24 RCTs involving 6188 patients were included. The network meta-analysis showed that there were no significant differences for the 4-week healing rate of duodenal ulcer treated with different PPI regimens except pantoprazle 40 mg/d versus lansoprazole 15 mg/d [Relative risk (RR) = 3.57; 95% confidence interval (CI) = 1.36–10.31)] and lansoprazole 30 mg/d versus lansoprazole 15 mg/d (RR = 2.45; 95% CI = 1.01–6.14). In comparison with H2 receptor antagonists (H2 RA), pantoprazole 40 mg/d and lansoprazole 30 mg/d significantly increase the healing rate (RR = 2.96; 95% CI = 1.78–5.14 and RR = 2.04; 95% CI = 1.13–3.53, respectively). There was no significant difference for the rate of adverse events between different regimens, including H2 RA for a duration of 4-week of follow up.Conclusion:There was no significant difference for the efficacy and tolerance between the ordinary doses of different PPIs with the exception of lansoprazle 15 mg/d.

A systematic review of the treatment of gastroesophageai reflux disease with mosapride in China

Objective To evaluate the efficacy and safety of mosapride in the treatment of gastroesophageal reflux disease (GERD). Methods Papers of PubMed,EMBASE,OVID,VIP Database and WANGFANG Data were searched and reviewed according to international Cochrane Collaboration.Results A total of 21 trials (1666 patients) were included.The treatment group was with mosapride and PPI,the control group was with single PPI or PPI and placebo.The Results of Meta analysis showed:for non-erosive negative reflux disease,there was no significant difference in efficacy between two groups.As for erosive esophagitis treated with mosapride (5mg):There was no significant difference in the 4-week healing rates between treatment group and control group (P =0.06).The 4-week symptom relief rate of treatment group was better than that of control group (P＜0.01).The 6-week healing rate of treatment group was better than that of control group (P＜0.01).The 6-week symptom relief rate of treatment group was better than that of control group (P＜0.01).There was no significant difference in the 8-week healing rate of esophagitis between treatment group and control group (P =0.05).The 8-week symptom relief rate of treatment group was better than that of control group (P＜0.01).For erosive esophagitis treated with mosapride 10mg,.The 8-week symptom relief rate of treatment group was better than that of control group (P=0.02).Conclusion According to the meta-analysis of these 21 trails,mosapride was safe and effective in the treatment of GERD.However due to the quality of the literatures,the above findings should be treated with caution. Key words: Benzamides; Gastroesophageal reflux; Computer systems; Drug evaluation; Metaanalysis

Diabetic Control Affects Healing Rates in Neuropathic and Vasculopathic Patients

Diabetic foot ulcers are among the most important complications of diabetes mellitus. In nearly 90% of persons who suffer limb loss from diabetes, ulcers precede amputation, and better and faster healing has been shown to reduce the frequency of amputations (Boulton et al., 2004). Ulcers are also associated with high mortality, and patients who have diabetes and foot ulcers have a 50% greater risk of dying than diabetic patients without a history of foot ulcers (Iversen et al., 2009). Poor healing is often observed in these patients. Therefore, a better understanding of which patients are likely to not heal with standard care and the reasons that these patients do not heal will help identify targets for intervention and indicate which patients may need advanced wound care modalities, such as engineered skin or hyperbaric oxygen. Baseline wound characteristics such as wound size, depth, stage, and duration, as well as 4-week healing rates, have been found to be predictive of the likelihood of complete healing (Margolis et al., 2002). Despite the fact that in vitro studies and animal models suggest that glycemia impairs healing, previous studies have not found hemoglobin A1c (HbA1c) levels to be correlated with healing; however, the study designs may have influenced these results. Using a novel study design, Christman and colleagues (2011, this issue) utilized electronic medical records from an active wound center to assess predictors of healing rates retrospectively. Delineation of wounded patients with diabetes into a “classic” neuropathic foot ulcer group and a complicated-wound group and multivariate analysis revealed that elevated HbA1c levels were associated with slower healing in patients with classic neuropathic diabetic foot ulcers and patients with peripheral vascular disease. Understanding at-risk populations has advantages in many areas, including focusing efforts and health-care dollars, improving treatment compliance, defining patients who need more advanced therapies, and identifying new therapeutic targets. Through the following questions, we examine this paper in greater detail. For brief answers, please refer to the supplementary information online .

Percent Change in Wound Area of Diabetic Foot Ulcers over a 4-Week Period Is a Robust Predictor of Complete Healing in a 12-Week Prospective Trial

To assess the ability of the 4-week healing rate to predict complete healing over a 12-week period in a large prospective multicenter trial of diabetic patients with foot ulceration. We examined the change in ulcer area over a 4-week period as a predictor of wound healing within 12 weeks in patients who were seen weekly in a prospective, randomized controlled trial. Wound area measurements at baseline and after 4 weeks were performed in 203 patients. The midpoint between the percentage area reduction from baseline at 4 weeks in patients healed versus those not healed at 12 weeks was found to be 53%. Subjects with a reduction in ulcer area greater than the 4-week median had a 12-week healing rate of 58%, whereas those with reduction in ulcer area less than the 4-week median had a healing rate of only 9% (P < 0.01). The absolute change in ulcer area at 4 weeks was significantly greater in healers versus nonhealers (1.5 versus 0.8 cm2, P < 0.02). The percent change in wound area at 4 weeks in those who healed was 82% (95% CI 70-94), whereas in those who failed to heal, the percent change in wound area was 25% (15-35; P < 0.001). The percent change in foot ulcer area after 4 weeks of observation is a robust predictor of healing at 12 weeks. This simple tool may serve as a pivotal clinical decision point in the care of diabetic foot ulcers for early identification of patients who may not respond to standard care and may need additional treatment.

Healing of Nonsteroidal Anti-inflammatory Drug-Associated Ulcers and Erosions, and Relief of Dyspeptic Symptoms: A Commentary on the New Data

Anumber of treatments are available for promoting the healing of gastric and duodenal ulcers associated with the ingestion of nonsteroidal anti-inflammatory drugs). These include the proton pump inhibitors and H2-receptor antagonists, which inhibit gastric acid secretion, and prostaglandin analogs, which suppress gastric acid and are also cytoprotective. A key issue, however, is what represents optimal therapy in peptic ulcer patients who must continue NSAID treatment. To date, the H2-receptor antagonists have been the most extensively studied therapeutic class in this disease area, but the data are conflicting. In a multicenter study by Lancaster-Smith et al, healing of NSAID-associated ulcers with ranitidine, 150 mg twice daily, was significantly lower in patients who continued their NSAID therapy when compared with those who stopped. At 8 weeks, gastric ulcers had healed in 63% of patients who continued NSAID therapy, compared with 95% who stopped. In duodenal ulcer, the 8-week healing rates were 84% in patients who continued NSAID therapy and 100% in those who stopped. In contrast, however, other studies have not shown such an effect of continued NSAID ingestion on ranitidine therapy. In a group of 67 patients, Manniche et al reported similar healing rates with either ranitidine, 150 mg twice daily, or sucralfate, 1 g four times daily, irrespective of whether NSAID therapy was discontinued. Similarly, in a separate study of 149 arthritic patients, the 4-week healing rates with ranitidine, 150 mg twice daily, in patients who continued or discontinued NSAID therapy were 67% and 68%, respectively, for gastric ulcer and 61% and 81%, respectively, for duodenal ulcer. In the same study, the 4-week healing rates in patients treated with placebo who discontinued NSAID therapy were 47% and 42% for gastric and duodenal ulcer, respectively. While prophylaxis of NSAID-associated gastroduodenal ulcers with the prostaglandin analog misoprostol is well documented, data are very limited on its acute use for healing, particularly in patients who continue to take NSAID therapy. Misoprostol, 200 mg four times daily, has been compared with placebo in a double-blind trial involving 77 patients with endoscopically verified gastric ulcer. In this study, the healing rate at 8 weeks was 90% with placebo. Thus, the cumulative healing rate with misoprostol was not better than with placebo at 8 weeks, although it was significantly higher at 4 weeks, possibly suggesting that misoprostol accelerates the healing of gastric ulcers. NSAID therapy was discontinued during this study, however. The efficacy of the proton pump inhibitor omeprazole is well established in the acute management of peptic ulcer disease, but there are only limited data for NSAIDassociated gastroduodenal ulcers. In a double-blind study by Walan et al, omeprazole, 20 mg once daily, was found to be superior to ranitidine, 150 mg twice daily, in healing gastric ulcers, including a subgroup of patients taking concomitant NSAID therapy. The overall healing rate with omeprazole was 69% after 4 weeks, and similarly, was 61% in the subgroup of patients who received concomitant NSAID therapy. In comparison, the overall 4-week healing rate with ranitidine was 59%, but only 32% in patients who were taking NSAIDs. This study suggested that gastric ulcer healing with ranitidine, but not omeprazole, was affected by concomitant NSAID ingestion; however, there were only 68 patients in the subgroup taking NSAIDs. Furthermore, Lauritsen et al have reported, in a double-blind study, that the healing of duodenal ulcers in NSAID users is similar with omeprazole, 20 and 40 mg once daily. In summary, there has been a lack of comparative studies of any size between potentially active drugs, particularly involving patients who need to continue NSAID therapy. The two new, large, randomized, double-blind, multicenter, controlled studies—Acid Suppression Trial: Ranitidine versus Omeprazole for NSAID-Associated Ulcer Treatment (ASTRONAUT) and Omeprazole versus Misoprostol of NSAID-Induced Ulcer Management (OMNIUM)—involved almost 1,500 patients who continued to take daily NSAID therapy. They have provided new comparative data on the efficacy and tolerability of original magnification, 20 and 40 mg once daily, ranitidine, 150 mg twice daily, and misoprostol, 200 mg four times daiFrom the Department of Medicine, University of Sydney, The Nepean Hospital, Penrith, New South Wales, Australia. Requests for reprints should be addressed to Nicholas J. Talley, MD, PhD, Division of Medicine, The Nepean Hospital, P.O. Box 63, Penrith, New South Wales 2751, Australia.

Ulcer Treatment–Regimens and Duration of Inhibition of Acid Secretion: How Long to Dose

The healing rate of duodenal and gastric ulcer depends on the duration of treatment. When a single drug is examined, there are considerable variations from study to study. The healing rate also depends on the type of drug used. It increases with an increasing degree of acid inhibition. Thus, the strongest acid inhibitor presently known, omeprazole, leads in patients with duodenal ulcer to 2-week healing rates of 65%, similar to the 4-week healing rate observed with H2-antagonists. If the aim is, however, to heal almost all ulcers at risk, then treatment should last for 4 weeks with omeprazole and 6 weeks with H2-antagonists. It has been claimed that eradication of Campylobacter pylori accelerates ulcer healing, but this is at present controversial. The duration of treatment depends on whether an endoscopy is performed at the end of treatment and on the presence or absence or risk factors. Treatment of duodenal ulcer should last 6 weeks with H2-antagonists or 4 weeks with omeprazole when no endoscopy is pe...