Double-blind, randomized, 8-week multicenter study of the efficacy and safety of STW 5-IIversus placebo in functional dyspepsia.

Background and Aim: Herbal products are widely used to treat patients with disorders of gut brain interaction but clinical efficacy and safety data for treatments lasting >4 weeks are widely lacking. We evaluated the efficacy and safety of 8 weeks of treatment with the herbal combination product STW 5-II for patients with functional dyspepsia (FD) meeting Rome II criteria. We also conducted a post hoc analysis including patients meeting Rome IV criteria for FD and evaluated the effect of the G-protein beta 3 (GNB3) subunit polymorphism (C825T) on therapeutic response. Methods: This multicenter, placebo-controlled, double-blind study included 272 FD patients meeting Rome II criteria in the intention-to-treat cohort and 266 meeting Rome IV criteria. We used the validated Gastrointestinal Symptom Score (GIS) to assess GI symptoms, defining response rate as the proportion of patients with ≥50% GIS improvement in at least three of four assessments. Results: After 8 weeks, the response rate was significantly higher in the STW 5-II group versus placebo (61.2% vs 45.1%, P = 0.008). Mean GIS non-significantly improved with STW 5-II treatment (7.9 ± 4.41 vs 6.7 ± 4.91 with placebo; P = 0.07). In the Rome IV subgroup analysis, STW 5-II yielded a better response rate (P = 0.01) versus placebo and greater postprandial distress symptom improvement (P = 0.04) versus placebo. Safety parameters did not differ between groups, and GNB3 status was not linked with therapeutic response. Conclusion: STW 5-II is efficacious, with no observed safety signals at up to 8 weeks of treatment in patients with FD meeting Rome II or IV criteria.

Early onset of efficacy in patients with functional and motility-related gastrointestinal disorders : A noninterventional study with Iberogast®.

STW 5 (Iberogast®; Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany) contains nine plant extracts and possesses well-documented overall efficacy in functional gastrointestinal disorders (FGID). Little is known about the onset of symptom relief. Twenty-nine centers in Germany recruited 272 patients with established FGID. These patients were treated with STW 5 for approximately 3 weeks in this noninterventional study. Patients assessed the severity of their gastrointestinal complaints before and at defined times after the intake of STW 5 (10 cm visual analogue scale; VAS). Fifteen minutes after the first dose, the severity of gastrointestinal complaints had decreased by 1.4 cm (mean; initial mean: 5.2 of 10 cm). After 1 h, more than 90% of the maximum effect of 3.2 cm on the 10 cm VAS had been reached. Most patients with symptoms experienced a marked improvement within 5, 15 or 30 min of taking STW 5. Absolute improvements were larger in patients with more pronounced baseline complaints. Subgroups with upper (80% of the study population) and lower FGID (20%) did not present major differences. Neither did subgroups by age and duration of complaints. Treatment with STW 5 resulted in rapid improvement of symptoms.

Modulation of gastrointestinal motility beyond metoclopramide and domperidone : Pharmacological and clinical evidence for phytotherapy in functional gastrointestinal disorders.

The prokinetic cisapride, an important therapeutic option in functional gastrointestinal (GI) disorders, was withdrawn from the market 15 years ago due to rare severe side effects. Likewise in 2014, the use of metoclopramide (MCP) and domperidone in functional GI disorders (FGID) was restricted, consequently leaving a therapeutic gap in clinical practice. A systematic review revealed that the herbal medicinal product (HMP) STW 5 presents a therapeutic option equivalent to MCP and cisapride. STW 5 is the only HMP for which efficacy has been shown in randomized controlled clinical trials (RCTs) in functional dyspepsia and irritable bowel syndrome, based on its multitarget effect on numerous etiological factors. Due to an outstanding favorable safety profile, STW 5 allows an effective and safe use in FGID without a limitation of the duration of the treatment.

STW 5, a phytopharmacon for patients with functional dyspepsia: results of a multicenter, placebo-controlled double-blind study.

BACKGROUND: Functional dyspepsia (FD) constitutes a complex picture with a variety of epigastric symptoms. No standard therapy is currently available for FD. OBJECTIVE: This multicenter, placebo-controlled, double-blind study evaluated the efficacy and tolerability of the herbal drug STW 5, mainly comprising a fresh plant extract from Iberis amara. METHODS: Patients with FD were included. Gastrointestinal endoscopy, H. pylori-status, and a 7-day run-in phase were required. A total of 315 patients were treated with 3 x 20 drops/day of either STW 5 or placebo. Symptom assessment: day 0, 2, 4, and 8 wk of treatment. The principal outcome criterion was the change in a validated Gastrointestinal Symptom Score (GIS). Symptom severity was rated using the Likert scale. RESULTS: A total of 315 patients remained in the safety population. Of them, 158 were treated with STW 5 and 157 with placebo. The intention-to-treat population comprised 308 patients. Dropout number was similar in both groups. GIS showed improvement during the treatment period. The STW 5 group improved 6.9+/-4.8 points up to day 56, placebo group by 5.9+/-4.3 (P<0.05). H. pylori did not influence the results. Drug tolerability and safety were similar in both groups. CONCLUSION: This placebo-controlled study with an 8-wk treatment period documents the efficacy of STW 5 in FD.

[Evidence-based medicine and phytotherapy for functional dyspepsia and irritable bowel syndrome: a systematic analysis of evidence for the herbal preparation Iberogast]. / Evidenz-basierte Medizin und Phytotherapie bei funktioneller Dyspepsie und Reizdarmsyndrom: Eine systematische Analyse der verfügbaren Evidenz zum Präparat Iberogast.

Functional gastrointestinal disorders like functional dyspepsia and irritable bowel syndrome are characterized by more or less specific symptoms and the absence of structural lesions to explain symptoms. Other studies suggest that abnormalities of specific gut function are linked to manifestation of symptoms. These abnormalities include disturbances of motility such as postprandial fundic relaxation, gastric emptying and disturbed visceral sensory function. The underlying pathophysiology is not fully understood. However, various studies point towards hereditary (or molecular) factors modified by environmental factors. Considering this broad spectrum of factors it is conceivable that treatments targeting a single mechanism are most likely to improve symptoms only in patients with a disturbance linked to this mechanism. Thus overall efficacy in the whole patient population is limited. Indeed, superiority of chemically defined treatments targeting a single receptor yield a benefit over placebo of between 10 and 15%. In recent years well-controlled studies have demonstrated superiority of specific herbal preparations. This in particular held true for combinations of various plant extracts or herbal extracts with a number of different active ingredients. However, efficacy of herbal treatment for functional GI disorders cannot be taken for granted and these drugs need to be rigorously tested for efficacy and safety. In this context, same standards apply as for conventional chemically defined medications.