Ambroxol 30mg tablets

ObjectiveTo evaluate the efficacy and safety of ambroxol hydrochloride and clenbuterol hydrochloride oral solution (AHCHOS) in pediatric patients with wheezing disorders and provide a comprehensive evidence map of the current clinical status.MethodsA literature search was conducted in PubMed, Embase, Cochrane Library, CNKI, Wanfang, and CBM to identify randomized controlled trials (RCTs) evaluating the efficacy and safety of AHCHOS in children with wheezing disorders. The clinical status was descriptively summarized. Meta-analyses for efficacy and safety outcomes were performed using a random-effects model in Review Manager 5.4. Outcomes were treatment effectiveness, times to symptom and clinical sign resolution, length of hospital stay, and adverse events (AEs). All time-related outcomes were reported in days.ResultsA total of 227 RCTs were included in the evidence mapping, 14 of which met the criteria for meta-analysis. Evidence mapping revealed a general increase in the number of studies from 2005 to a peak in 2012, followed by a decline. Most studies were conducted in eastern China, particularly in Henan Province. Meta-analysis results demonstrated that combination therapy with AHCHOS significantly improved the overall response rate [risk ratio (RR) 1.26, 95% confidence interval (CI) 1.10-1.44] and significant effective rate (RR 1.55, 95% CI 1.36-1.76). It also significantly reduced the duration (days) of coughing [mean difference (MD) -1.40, 95% CI -1.75 to -1.06], wheezing (MD -1.88, 95% CI -2.50 to -1.26), cough phlegm (MD -2.00, 95% CI -2.76 to -1.24), wet lung sounds (MD -1.82, 95% CI -2.33 to -1.30), pulmonary rales (MD -2.27, 95% CI -2.90 to -1.64), and hospital stay (MD -1.13, 95% CI -1.45 to -0.82). Furthermore, AHCHOS did not increase the risk of AEs compared with conventional treatment alone.ConclusionCombination therapy with AHCHOS was associated with modest but statistically significant improvements in symptom resolution and length of hospital stay compared with conventional treatment alone. However, all included studies were conducted in China, which may limit the generalizability of the findings. In addition, no definitive conclusions regarding safety could be drawn due to limited and inconsistent adverse event reporting. Further safety assessments in future trials are warranted.Systematic review registrationThe protocol has been registered on INPLASY (INPLASY202480121).

Abstract licence: CC BY

Abstract Background To date, no disease modifying therapies are available for Parkinson’s disease (PD). Since PD is the second most prevalent neurodegenerative disorder, there is a high demand for such therapies. Both environmental and genetic risk factors play an important role in the etiology and progression of PD. The most common genetic risk factor for PD is a mutation in the GBA1(GBA)-gene, encoding the lysosomal enzyme glucocerebrosidase (GCase). The mucolytic ambroxol is a repurposed drug, which has shown the property to upregulate GCase activity in-vitro and in-vivo. Ambroxol therefore has the potency to become a disease modifying therapy in PD, which was the reason to design this randomized controlled trial with ambroxol in PD patients. Methods This trial is a single-center, double-blind, randomized, placebo-controlled study, including 80 PD patients with a GBA mutation, receiving either ambroxol 1800 mg/day or placebo for 48 weeks. The primary outcome measure is the Unified Parkinson’s Disease Rating Scale motor subscore (part III) of the Movement Disorder Society (MDS-UPDRSIII) in the practically defined off-state at 60 weeks (after a 12-week washout period). Secondary outcomes include a 3,4-dihydroxy-6-18F-fluoro-I-phenylalanine ([18F]FDOPA) PET-scan of the brain, Magnetic Resonance Imaging (with resting state f-MRI and Diffusion Tensor Imaging), GCase activity, both intra- and extracellularly, sphingolipid profiles in plasma, Montreal Cognitive Assessment (MoCA), quality of life (QoL) measured by the Parkinson’s Disease Questionnaire (PDQ-39) and the Non-Motor Symptom Scale (NMSS) questionnaire. Discussion Ambroxol up to 1200 mg/day has shown effects on human cerebrospinal fluid endpoints, which supports at least passage of the blood-brain-barrier. The dose titration in this trial up to 1800 mg/day will reveal if this dose level is safe and also effective in modifying the course of the disease. Trial registration NCT05830396. Registration date: March 20, 2023.

Abstract licence: CC BY 4.0