1.
Efficacy and Safety of the Adjuvant Use of Probiotic Bacillus clausii Strains in Pediatric Irritable Bowel Syndrome: A Randomized, Double-Blind, Placebo-Controlled Study.
Vázquez-Frias, R, Consuelo-Sánchez, A, Acosta-Rodríguez-Bueno, CP, Blanco-Montero, A, Robles, DC, Cohen, V, Márquez, D, Perez, M
Paediatric drugs. 2023;25(1):115-126
-
-
-
Free full text
-
Plain language summary
Irritable bowel syndrome (IBS) is considered both a health and a socioeconomic burden. Curative treatment for IBS is currently not available and current management strategies vary. Gut microbiota dysbiosis is increasingly considered as a vital factor in the etiopathogenetic of IBS; thus, gut microbiota are a potential therapeutic target. The aim of this study was to investigate the efficacy and safety of Bacillus clausii plus conventional treatment, compared with placebo plus conventional treatment, in children with IBS in Mexico. This study is a phase III, multicentre, randomised, placebo-controlled, double-blind, parallel clinical trial. Patients (n=259) were centrally randomised 1:1 to treatment with either B. clausii or placebo. Results show that IBS symptom relief in children was very high in both groups (B. clausii and placebo). In fact, there weren’t any significant differences between groups for proportion of patients with clinical improvements at Week 8 or any of the key secondary endpoints. Furthermore, the adverse event profile was similar between groups. Authors conclude that their study was not able to demonstrate the efficacy of B. clausii as an adjuvant to conventional treatment of patients with IBS.
Abstract
OBJECTIVES Current irritable bowel syndrome (IBS) treatments have limited efficacy and probiotics like Bacillus clausii (B. clausii) were found to be effective in the management of several gastrointestinal disorders. This phase III trial assessed the efficacy and safety of adding B. clausii (four strains: O/C, N/R, SIN, T), versus placebo, to conventional treatment of pediatric IBS in Mexico. METHODS Patients aged 6-17 years 11 months with IBS (Rome IV) for at least 2 months were randomized to receive either B. clausii (oral suspension, total dose 4 billion spores/day) or placebo once daily for 8 weeks. All patients also received conventional treatment. The primary endpoint was the difference in the proportion of patients with clinical improvements at Week 8 (Global Assessment Questions [GAQ]). Secondary endpoints included responders by Subject's Global Assessment of Relief for Children with IBS (SGARC); number/consistency of stools; abdominal distention/bloating; abdominal pain/intensity; and IBS behavior. RESULTS 73.6% (95% confidence interval [CI] 67.3-80.0; B. clausii n = 129) and 78.5% (95% CI 72.5-84.4; placebo n = 130) of patients had symptom improvement (p = 0.8182). For Week 8 SGARC, 19.2% (B. clausii) and 20.9% (placebo) reported complete symptom relief. Stool evaluations, bloating, abdominal pain/intensity, and IBS behavior were similar between groups. Both treatments were well tolerated. CONCLUSION No significant differences in efficacy between B. clausii and placebo were demonstrated in addition to conventional treatment. The sample size calculation was based on an expected placebo/conventional treatment response of 30-40%. However, the actual treatment response observed was 80% and, thus, a study with larger population would be warranted. In addition, this study was conducted during the COVID-19 pandemic, when such controlled social conditions may have resulted in better diet, greater family stability, less psychological stress, and lower risk of infections exacerbating IBS, thereby improving symptoms in both groups. EUDRACT NUMBER 2018-004519-31.
2.
Safety and Tolerability of SER-109 as an Investigational Microbiome Therapeutic in Adults With Recurrent Clostridioides difficile Infection: A Phase 3, Open-Label, Single-Arm Trial.
Sims, MD, Khanna, S, Feuerstadt, P, Louie, TJ, Kelly, CR, Huang, ES, Hohmann, EL, Wang, EEL, Oneto, C, Cohen, SH, et al
JAMA network open. 2023;6(2):e2255758
-
-
-
Free full text
-
Plain language summary
Clostridioides difficile infection (CDI) is most commonly caused by treatment with broad-spectrum antibiotics. Antibiotic treatment of CDI is generally successful but recurrences of CDI occur in 15-25% of patients after the first episode, and up to 40% of patients with a previous recurrence. This is thought to be due to persistent microbiome disruption, including a depletion of Firmicutes bacteria. The aim of this single-arm, open-label trial was to evaluate the safety and effectiveness of an investigational, microbiome therapeutic composed of purified Firmicutes spores (SER-109) to prevent CDI recurrences. 263 patients were enrolled in the study and received SER-109 on 3 consecutive days, started within 4 days of completion of antibiotic treatment for CDI recurrence. Follow-up was 24 weeks. Most patients were aged 65 years or older and had a high prevalence of comorbidities. There were no reports of serious adverse events which were considered related to SER-109. By week 24, 36 patients (13.7%) had experienced a CDI recurrence. This was independent of demographics, type of antibiotic treatment and number of prior recurrences. The authors concluded that the data suggest a role of SER-109 in the management of recurrent CDI.
Abstract
IMPORTANCE A safe and effective treatment for recurrent Clostridioides difficile infection (CDI) is urgently needed. Antibiotics kill toxin-producing bacteria but do not repair the disrupted microbiome, which promotes spore germination and infection recurrence. OBJECTIVES To evaluate the safety and rate of CDI recurrence after administration of investigational microbiome therapeutic SER-109 through 24 weeks. DESIGN, SETTING, AND PARTICIPANTS This phase 3, single-arm, open-label trial (ECOSPOR IV) was conducted at 72 US and Canadian outpatient sites from October 2017 to April 2022. Adults aged 18 years or older with recurrent CDI were enrolled in 2 cohorts: (1) rollover patients from the ECOSPOR III trial who had CDI recurrence diagnosed by toxin enzyme immunoassay (EIA) and (2) patients with at least 1 CDI recurrence (diagnosed by polymerase chain reaction [PCR] or toxin EIA), inclusive of their acute infection at study entry. INTERVENTIONS SER-109 given orally as 4 capsules daily for 3 days following symptom resolution after antibiotic treatment for CDI. MAIN OUTCOMES AND MEASURES The main outcomes were safety, measured as the rate of treatment-emergent adverse events (TEAEs) in all patients receiving any amount of SER-109, and cumulative rates of recurrent CDI (toxin-positive diarrhea requiring treatment) through week 24 in the intent-to-treat population. RESULTS Of 351 patients screened, 263 were enrolled (180 [68.4%] female; mean [SD] age, 64.0 [15.7] years); 29 were in cohort 1 and 234 in cohort 2. Seventy-seven patients (29.3%) were enrolled with their first CDI recurrence. Overall, 141 patients (53.6%) had TEAEs, which were mostly mild to moderate and gastrointestinal. There were 8 deaths (3.0%) and 33 patients (12.5%) with serious TEAEs; none were considered treatment related by the investigators. Overall, 23 patients (8.7%; 95% CI, 5.6%-12.8%) had recurrent CDI at week 8 (4 of 29 [13.8%; 95% CI, 3.9%-31.7%] in cohort 1 and 19 of 234 [8.1%; 95% CI, 5.0%-12.4%] in cohort 2), and recurrent CDI rates remained low through 24 weeks (36 patients [13.7%; 95% CI, 9.8%-18.4%]). At week 8, recurrent CDI rates in patients with a first recurrence were similarly low (5 of 77 [6.5%; 95% CI, 2.1%-14.5%]) as in patients with 2 or more recurrences (18 of 186 [9.7%; 95% CI, 5.8%-14.9%]). Analyses by select baseline characteristics showed consistently low recurrent CDI rates in patients younger than 65 years vs 65 years or older (5 of 126 [4.0%; 95% CI, 1.3%-9.0%] vs 18 of 137 [13.1%; 95% CI, 8.0%-20.0%]) and patients enrolled based on positive PCR results (3 of 69 [4.3%; 95% CI, 0.9%-12.2%]) vs those with positive toxin EIA results (20 of 192 [10.4%; 95% CI, 6.5%-15.6%]). CONCLUSIONS AND RELEVANCE In this trial, oral SER-109 was well tolerated in a patient population with recurrent CDI and prevalent comorbidities. The rate of recurrent CDI was low regardless of the number of prior recurrences, demographics, or diagnostic approach, supporting the beneficial impact of SER-109 for patients with CDI. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT03183141.