Carbocisteine 750mg capsules

Background: COPD is the fourth leading cause of death in the world. It is a common, progressive, treatable and preventable disease. The exacerbation of COPD is associated with the peripheral muscle force, forced expiratory volume in 1 second (FEV 1 ), the quality of life and mortality. Many studies indicated that the mucoactive medicines could reduce the exacerbations of COPD. This study summarized the efficacy of carbocisteine as a treatment for COPD. Methods: We searched the randomized controlled trials (RCTs) following electronic bibliographic databases: MedLine, Embase, Cochrane Library and Web of Science. We additionally searched gray literature database: OpenSIGLE. We also additionally searched the clinical trial registers: ClinicalTrials.gov register and International Clinical Trials Registry Platform Search Portal. We used RCTs to assess the efficacy of the treatments. We included studies of adults (older than 18 years) with COPD. We excluded studies that were published as protocol or written in non-English language (Number 42016047078). Findings: Our findings included data from four studies involving 1,357 patients. There was a decrease in the risk of the rate of total number of exacerbations with carbocisteine compared with placebo (-0.43; 95% confidence interval [CI] -0.57, -0.29, P <0.01). Carbocisteine could also improve the quality of life (-6.29; 95% CI -9.30, -3.27) and reduce the number of patients with at least one exacerbation (0.86; 95% CI 0.78, 0.95) compared with placebo. There was no significant difference in the FEV 1 and adverse effects and the rate of hospitalization. Interpretation: Long-term use of carbocisteine (500 mg TID) may be associated with lower exacerbation rates, the smaller number of patients with at least one exacerbation and higher quality of life of patients with COPD. Keywords: COPD, carbocysteine, systematic review, meta-analysis, exacerbation, humans, drug-related side effects and adverse reactions, respiratory function tests

Abstract licence: CC BY-NC 3.0

This systematic review and meta-analysis aimed to evaluate the efficacy and safety of carbocisteine in reducing chronic obstructive pulmonary disease (COPD) exacerbations based on evidence from randomized controlled trials (RCTs). A comprehensive literature search was conducted across PubMed, Embase, Cochrane Library, and ClinicalTrials.gov. RCTs comparing carbocisteine (1500 mg/day) with placebo in COPD patients, with a minimum follow-up of six months, were included. Data on exacerbation rates and adverse events were extracted and analyzed using a random-effects model. Four RCTs involving 1746 patients met inclusion criteria. Pooled analysis showed that carbocisteine significantly reduced the annual rate of acute exacerbations compared to placebo (WMD = −0.40; 95% CI: −0.69 to −0.11), with no significant increase in adverse events (OR = 1.02; 95% CI: 0.76 to 1.37). Mechanistically, carbocisteine improves mucociliary clearance, suppresses airway inflammation, reduces oxidative stress, and may hinder bacterial colonization. Carbocisteine is associated with a significant reduction in COPD exacerbations and demonstrates a favorable safety profile. It may serve as an effective adjunctive therapy in patients with frequent exacerbations and mucus hypersecretion.

Abstract licence: CC BY 4.0

BackgroundCurrent guidelines for the management of bronchiectasis (BE) highlight the lack of evidence to recommend mucoactive agents, such as hypertonic saline (HTS) and carbocisteine, to aid sputum removal as part of standard care. We hypothesise that mucoactive agents (HTS or carbocisteine, or a combination) are effective in reducing exacerbations over a 52-week period, compared to usual care.MethodsThis is a 52-week, 2 × 2 factorial, randomized, open-label trial to determine the clinical effectiveness and cost effectiveness of HTS 6% and carbocisteine for airway clearance versus usual care - the Clinical and cost-effectiveness of hypertonic saline (HTS 6%) and carbocisteine for airway clearance versus usual care (CLEAR) trial. Patients will be randomised to (1) standard care and twice-daily nebulised HTS (6%), (2) standard care and carbocisteine (750 mg three times per day until visit 3, reducing to 750 mg twice per day), (3) standard care and combination of twice-daily nebulised HTS and carbocisteine, or (4) standard care. The primary outcome is the mean number of exacerbations over 52 weeks. Key inclusion criteria are as follows: adults with a diagnosis of BE on computed tomography, BE as the primary respiratory diagnosis, and two or more pulmonary exacerbations in the last year requiring antibiotics and production of daily sputum.DiscussionThis trial’s pragmatic research design avoids the significant costs associated with double-blind trials whilst optimising rigour in other areas of trial delivery. The CLEAR trial will provide evidence as to whether HTS, carbocisteine or both are effective and cost effective for patients with BE.Trial registrationEudraCT number: 2017-000664-14 (first entered in the database on 20 October 2017).ISRCTN.com, ISRCTN89040295. Registered on 6 July/2018.Funder: National Institute for Health Research, Health Technology Assessment Programme (15/100/01).Sponsor: Belfast Health and Social Care Trust.Ethics Reference Number: 17/NE/0339.Protocol version: v3.0 Final_14052018.

Abstract licence: CC BY 4.0

Background: Current guidelines for the management of bronchiectasis (BE) highlight the lack of evidence to recommend mucoactive agents, such as hypertonic saline (HTS) and carbocisteine, to aid sputum-removal as part of standard care. We hypothesise that mucoactive agents (HTS or cabocisteine, or a combination) are effective in reducing exacerbations over a 52-week period, compared to usual care. Methods A 52-week, 2x2 factorial randomised open label trial to determine the clinical and cost-effectiveness of HTS 6% and carbocisteine for airway clearance versus usual care: CLEAR (clinical and cost-effectiveness of hypertonic saline (HTS 6%) and carbocisteine for airway clearance versus usual care). Patients will be randomised to either (i) Standard care and twice daily nebulised HTS (6%), (ii) Standard care and carbocisteine (750mg three times per day until visit 3 reducing to 750mg twice per day), (iii) Standard care and combination of twice-daily nebulised HTS and carbocisteine, or (iv) Standard care. The primary outcome is the mean number of exacerbations over 52 weeks. Key inclusion criteria: adults with a diagnosis of BE on computed tomography scans, BE as the primary respiratory diagnosis, two or more pulmonary exacerbations in the last year requiring antibiotics and production of daily sputum. Discussion This trial’s pragmatic research design avoids the significant costs associated with double-blind trials whilst optimising rigor in other areas of trial-delivery. CLEAR will provide evidence as to whether HTS, carbocisteine or both are effective and cost-effective for BE patients.

Abstract licence: CC BY 4.0

Background Usual airway clearance management in critically ill patients with acute respiratory failure includes suctioning, humidification, use of isotonic saline, and respiratory physiotherapy techniques. Escalation to use of mucoactives occurs when secretions are difficult to clear. Use of mucoactives in clinical practice for this patient population is extensive, yet empirical and variable. Carbocisteine and hypertonic saline are the most used agents, but evidence for their effectiveness is absent or minimal. The lack of existing large-scale randomised trials comparing mucoactives to usual airway clearance management alone in critically ill patients with acute respiratory failure highlights the urgency and necessity of this study. Aim To determine whether the use of mucoactives in critically ill patients with acute respiratory failure improves clinical outcomes and is cost effective, compared to usual airway clearance management alone. Methods A UK multi-centre, 2x2 factorial, randomised, controlled, open-label, Phase 3, pragmatic, clinical and cost effectiveness trial with internal pilot. The target sample is 1956 critically ill adults. Participants will be equally allocated across four trial arms. All participants will receive usual airway clearance management. In three intervention groups, participants will receive either carbocisteine, hypertonic saline, or a combination of carbocisteine and hypertonic saline. In the fourth comparator group, participants will receive usual airway clearance management alone. The primary outcome is the duration of mechanical ventilation with secondary clinical, safety, and health resource utilisation outcomes. The trial will be reported in accordance with CONSORT guidelines. Ethical approval was granted by Leeds East (Yorkshire & The Humber) Research Ethics Committee (reference 21/YH/0234) on 28th October 2021. All participants will provide written, informed consent via either Personal or Professional Legal Representatives, and subsequently directly once capacity is regained. Trial registration Main trial: ISRCTN17683568, https://www.isrctn.com/ISRCTN17683568, 25th November 2021 Study Within A Trial: ISRCTN16675252, https://www.isrctn.com/ISRCTN16675252, 3rd November 2021 EudraCT Number, 2021-003763-94

Abstract licence: CC BY 4.0

The role for S-carboxymethylcysteine (carbocisteine) in the management of chronic obstructive pulmonary disease C Hooper, J CalvertNorth Bristol Lung Centre, Southmead Hospital, Bristol, UKAbstract: Prescription of mucoactive drugs for chronic obstructive pulmonary disease (COPD) is increasing. This development in clinical practice arises, at least in part, from a growing understanding of the important role that exacerbation frequency, systemic inflammation and oxidative stress play in the pathogenesis of respiratory disease. S-carboxymethylcysteine (carbocisteine) is the most frequently prescribed mucoactive agent for long-term COPD use in the UK. In addition to its mucoregulatory activity, carbocisteine exhibits free-radical scavenging and anti-inflammatory properties. These characteristics have stimulated interest in the potential that this and other mucoactive drugs may offer for modification of the disease processes present in COPD. This article reviews the pharmacology, in vivo and in vitro properties, and clinical trial evidence for carbocisteine in the context of guidelines for its use and the current understanding of the pathogenic processes that underlie COPD.Keywords: carbocisteine, chronic obstructive pulmonary disease (COPD), exacerbation, free radicals, inflammation, mucolytic, oxidative stress, S-carboxymethylcysteine

Abstract licence: CC BY-NC 3.0