BAY 2253651 for the treatment of obstructive sleep apnoea: a multicentre, double-blind, randomised controlled trial (SANDMAN).
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SUBMITTER: Gaisl T
PROVIDER: S-EPMC8607905 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:IntroductionObstructive sleep apnoea (OSA) is characterised by a loss of neuromuscular tone of the upper airway dilator muscles while asleep. This study investigated the effectiveness of transcutaneous electrical stimulation in patients with OSA.Patients and methodsThis was a randomised, sham-controlled crossover trial using transcutaneous electrical stimulation of the upper airway dilator muscles in patients with confirmed OSA. Patients were randomly assigned to one night of sham stimulation and one night of active treatment. The primary outcome was the 4% oxygen desaturation index, responders were defined as patients with a reduction >25% in the oxygen desaturation index when compared with sham stimulation and/or with an index <5/hour in the active treatment night.ResultsIn 36 patients (age mean 50.8 (SD 11.2) years, male/female 30/6, body mass index median 29.6 (IQR 26.9-34.9) kg/m(2), Epworth Sleepiness Scale 10.5 (4.6) points, oxygen desaturation index median 25.7 (16.0-49.1)/hour, apnoea-hypopnoea index median 28.1 (19.0-57.0)/hour) the primary outcome measure improved when comparing sham stimulation (median 26.9 (17.5-39.5)/hour) with active treatment (median 19.5 (11.6-40.0)/hour; p=0.026), a modest reduction of the mean by 4.1 (95% CI -0.6 to 8.9)/hour. Secondary outcome parameters of patients' perception indicated that stimulation was well tolerated. Responders (47.2%) were predominantly from the mild-to-moderate OSA category. In this subgroup, the oxygen desaturation index was reduced by 10.0 (95% CI 3.9 to 16.0)/hour (p<0.001) and the apnoea-hypopnoea index was reduced by 9.1 (95% CI 2.0 to 16.2)/hour (p=0.004).ConclusionTranscutaneous electrical stimulation of the pharyngeal dilators during a single night in patients with OSA improves upper airway obstruction and is well tolerated.Trial registration numberNCT01661712.
| S-EPMC5036236 | biostudies-literature
Project description:PurposeRetinal microvascular endothelial dysfunction is thought to be of importance in the development of ocular vascular diseases. Obstructive sleep apnoea (OSA) causes macrovascular endothelial dysfunction, but the effect of OSA on retinal microvascular endothelial function is not known. We aimed to determine the effect of OSA on retinal microvascular function.MethodsWe conducted a multi-centre, double-blind, randomised, parallel, controlled trial in patients with known moderate-to-severe OSA, established on continuous positive airway pressure (CPAP). Participants were randomised to 14 nights of either continued CPAP or sham CPAP to generate a return of OSA. Retinal vascular responses to flickering light were measured using dynamic vessel analysis both at baseline and after 14 nights of intervention. The primary outcome was the change from baseline to follow-up in the area under the curve of the arteriolar response to flickering light, sham CPAP versus continued CPAP.ResultsNineteen patients were randomised to sham CPAP, and 18 patients were randomised to continued CPAP. There was no significant effect of CPAP withdrawal and return of OSA on retinal responses, with a change in the area under the curve of the arteriole response to flickering light of + 3.8 arbitrary units (95% CI - 10.6 to + 18.2, p = 0.59), sham CPAP versus continued CPAP.ConclusionsCPAP withdrawal and a return of OSA had no significant effect on retinal microvascular responses. This contrasts with the effect of CPAP withdrawal on macrovascular endothelial function and suggests that OSA has different effects on macrovascular and microvascular endothelial function. ISRCTN 78082983, 23/10/2014, Prospectively registered.
| S-EPMC8866916 | biostudies-literature
Project description:IntroductionObstructive sleep apnoea (OSA) is a highly prevalent disease that causing systemic hypertension. Furthermore, altitude-dependent hypobaric hypoxic condition and Tibetan ethnicity have been associated with systemic hypertension independent of OSA, therefore patients with OSA living at high altitude might be at profound risk to develop systemic hypertension. Acetazolamide has been shown to decrease blood pressure, improve arterial oxygenation and prevent high altitude periodic breathing in healthy volunteers ascending to high altitude and decrease blood pressure in patients with systemic hypertension at low altitude. However, the effect of acetazolamide on 24-hour blood pressure, sleep-disordered disturbance and daytime cognitive performance in patients with OSA permanently living at high altitude has not been studied.Methods and analysisThis study protocol describes a randomised, placebo-controlled, double-blinded crossover trial. Highland residents of both sexes, aged 30-60 years, Tibetan ethnicity, living at an elevation of 3650 m and apnoea-hypopnoea index over 15/hour will be included. Participants will be randomly assigned to a 2×2 week treatment period starting with 750 mg/day acetazolamide followed by placebo treatment or vice versa, separated by a 1-week wash-out phase. Clinical assessments, 24-hour ambulatory blood pressure monitoring (ABPM), polysomnography (PSG), near-infrared spectroscopy, nocturnal fluid shift and cognitive performance will be assessed before and at the end of each treatment period. The primary outcome will be the difference in 24-hour mean blood pressure between acetazolamide therapy and placebo; secondary outcomes will be the difference in other 24-hour ABPM-derived parameters, PSG-derived parameters, cognitive performance and overnight change in different segments of fluid volume between acetazolamide therapy and placebo. Accounting for potential dropouts, 40 participants will be recruited.Ethics and disseminationThe protocol was approved by the West China Hospital of Sichuan University Biomedical Research Ethics Committee. Recruitment will start in spring 2022. Dissemination of the results include presentations at conferences and publications in peer-reviewed journals.Trial registration numberChiCTR2100049304.
| S-EPMC8905944 | biostudies-literature
Project description:BackgroundA post hoc analysis of the MERGE trial was conducted, to investigate whether sex differences are evident at the mildest end of the disease spectrum, for symptoms associated with obstructive sleep apnoea (OSA) and the response to continuous positive airway pressure (CPAP) treatment.MethodsMERGE participants with mild OSA (apnoea-hypopnoea index 5-15 events·h-1; American Academy of Sleep Medicine 2012 criteria) were randomised to either CPAP plus standard care (sleep hygiene counselling) or standard care alone for 3 months. Quality of life (QoL) was measured by questionnaires completed before and after the 3 months. This post hoc analysis of participants of the MERGE trial compared the symptom presentation, and response to CPAP, between the sexes.Results233 patients were included; 71 (30%) were female. Females were more symptomatic at baseline in all QoL questionnaires. Specifically, females had lower 36-item Short-Form Health Survey (SF-36) Vitality scores (mean±sd 39.1±10.1 versus 44.8±10.3) and higher Epworth Sleepiness Scale (ESS) scores (mean±sd 11.0±4.2 versus 9.5±4.4). Both sexes experienced snoring, but more females reported fatigue and more males reported witnessed apnoeas. All symptoms improved with CPAP for both sexes; however, females had larger improvements in SF-36 Vitality scores, which was the primary outcome of the MERGE trial (mean change 9.4 (95% CI 6.8-12.0) versus 6.0 (95% CI 4.3-7.7); p=0.034), and ESS (mean change -4.1 (95% CI -5.1- -3.0) versus -2.5 (95% CI -3.1- -1.8); p=0.015), after adjustment for baseline scores and CPAP usage.ConclusionsSex differences are apparent in patients with mild OSA. Females experience worse QoL symptoms than males at presentation to the sleep clinic; however, these improve significantly with CPAP treatment.
| S-EPMC10851951 | biostudies-literature
Project description:ObjectivesMany clinical studies have indicated that obstructive sleep apnoea (OSA), the most common chronic sleep disorder, may affect neurocognitive function, and that treatment for continuous positive airway pressure (CPAP) has some neurocognitive protective effects against the adverse effects of OSA. However, the effects of CPAP treatment on neurocognitive architecture and function remain unclear. Therefore, this multicentre trial was designed to investigate whether and when neurocognitive architecture and function in patients with OSA can be improved by CPAP treatment and to explore the role of gut microbiota in improving neurocognitive function during treatment.Methods/designThis study will be a multicentre, randomised, controlled trial with allocation concealment and assessor blinding. A total of 148 eligible patients with moderate to severe OSA will be enrolled from five sleep centres and randomised to receive CPAP with best supportive care (BSC) intervention or BSC intervention alone. Cognitive function, structure and function of brain regions, gut microbiota, metabolites, biochemical variables, electrocardiography, echocardiography, pulmonary function and arterial stiffness will be assessed at baseline before randomisation and at 3, 6 and 12 months.Ethics and disseminationThis study has been approved by the Medical Ethics Committee of Shanghai Jiao Tong University Affiliated Sixth People's Hospital (approval number 2015-79). The results from this study will be published in peer-reviewed journals and at relevant conferences.Trial registration numberNCT02886156; pre-results.
| S-EPMC5729992 | biostudies-literature
Project description:IntroductionChronic obstructive pulmonary disease (COPD) represents one of the leading causes of death worldwide. Published clinical trials suggest that the Chinese patent herbal medicine Shufeng Jiedu capsule (SFJD) is safe and may be effective for treating acute exacerbations of COPD (AECOPD). However, these effects have been reported with low or very low certainty evidence. This trial aims to evaluate the effectiveness and safety of SFJD for AECOPD.Methods and analysisThis study is designed as a multicentre, randomised, double-blind, placebo-controlled trial. Three hundred patients with moderate or severe hospitalised AECOPD will be recruited in Beijing, Shanghai and Hefei. Participants will be randomly assigned to SFJD and usual care or placebo and usual care at a ratio of 1:1. SFJD and placebo will be administered orally four capsules three times daily for 7 consecutive days followed by an 8-week follow-up period. The primary outcome will be COPD symptom severity as measured by the EXAcerbation of Chronic Pulmonary Disease Tool score. Secondary outcomes include clinical symptoms, quality of life, length of hospital stay, a total dose of antibiotics, the frequency of recurrence of AECOPD, haematological biomarkers, death and adverse events. This study will answer the question of whether SFJD was safe to use and will improve symptoms in people with AECOPD, and will therefore reduce the necessity for antibiotics, the risk and duration of admission to hospital, and the risk of recurrence.Ethics and disseminationThe ethics committee of the first affiliated hospital of Anhui Medical University, Beijing University of Chinese Medicine affiliated Dongzhimen hospital and fifth people's hospital of Shanghai Fudan University approved the study protocol. Informed written consent will be obtained from all the participants. The results of this trial will be disseminated at academic conferences and in peer-reviewed publications.Trial registration numberISRCTN99049821.
| S-EPMC10546128 | biostudies-literature
Project description:(1) Background: osteopathic manipulation of the sphenopalatine ganglia (SPG) blocks the action of postganglionic sensory fibres. This neuromodulation can reduce nasal obstruction and enhance upper airway stability. We investigated the manipulation of the SPG in 31 patients with obstructive sleep apnoea syndrome (OSAS); (2) Methods: Randomised, controlled, double-blind, crossover study. Participants received active (AM), then sham manipulation (SM), or vice versa. The primary endpoint was apnoea-hypopnoea index (AHI). Secondary endpoints were variation of nasal obstruction evaluated by peak nasal inspiratory flow (PNIF) and upper airways stability evaluated by awake critical closing pressure [awake Pcrit]), at 30 min and 24 h. Schirmer's test and pain were assessed immediately post-manipulation. Tactile/gustatory/olfactory/auditory/nociceptive/visual sensations were recorded. Adverse events were collected throughout. (3) Results: SPG manipulation did not reduce AHI (p = 0.670). PNIF increased post-AM but not post-SM at 30 min (AM-SM: 18 [10; 38] L/min, p = 0.0001) and 24 h (23 [10; 30] L/min, p = 0.001). There was no significant difference on awake Pcrit (AM-SM) at 30 min or 24 h). Sensations were more commonly reported post-AM (100% of patients) than post-SM (37%). Few adverse events and no serious adverse events were reported. (4) Conclusions: SPG manipulation is not supported as a treatment for OSAS but reduced nasal obstruction. This effect remains to be confirmed in a larger sample before using this approach to reduce nasal congestion in CPAP-treated patients or in mild OSAS.
| S-EPMC8745154 | biostudies-literature
Project description:BackgroundNo specific antiviral drug has been proven effective for treatment of patients with severe coronavirus disease 2019 (COVID-19). Remdesivir (GS-5734), a nucleoside analogue prodrug, has inhibitory effects on pathogenic animal and human coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro, and inhibits Middle East respiratory syndrome coronavirus, SARS-CoV-1, and SARS-CoV-2 replication in animal models.MethodsWe did a randomised, double-blind, placebo-controlled, multicentre trial at ten hospitals in Hubei, China. Eligible patients were adults (aged ?18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection, with an interval from symptom onset to enrolment of 12 days or less, oxygen saturation of 94% or less on room air or a ratio of arterial oxygen partial pressure to fractional inspired oxygen of 300 mm Hg or less, and radiologically confirmed pneumonia. Patients were randomly assigned in a 2:1 ratio to intravenous remdesivir (200 mg on day 1 followed by 100 mg on days 2-10 in single daily infusions) or the same volume of placebo infusions for 10 days. Patients were permitted concomitant use of lopinavir-ritonavir, interferons, and corticosteroids. The primary endpoint was time to clinical improvement up to day 28, defined as the time (in days) from randomisation to the point of a decline of two levels on a six-point ordinal scale of clinical status (from 1=discharged to 6=death) or discharged alive from hospital, whichever came first. Primary analysis was done in the intention-to-treat (ITT) population and safety analysis was done in all patients who started their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT04257656.FindingsBetween Feb 6, 2020, and March 12, 2020, 237 patients were enrolled and randomly assigned to a treatment group (158 to remdesivir and 79 to placebo); one patient in the placebo group who withdrew after randomisation was not included in the ITT population. Remdesivir use was not associated with a difference in time to clinical improvement (hazard ratio 1·23 [95% CI 0·87-1·75]). Although not statistically significant, patients receiving remdesivir had a numerically faster time to clinical improvement than those receiving placebo among patients with symptom duration of 10 days or less (hazard ratio 1·52 [0·95-2·43]). Adverse events were reported in 102 (66%) of 155 remdesivir recipients versus 50 (64%) of 78 placebo recipients. Remdesivir was stopped early because of adverse events in 18 (12%) patients versus four (5%) patients who stopped placebo early.InterpretationIn this study of adult patients admitted to hospital for severe COVID-19, remdesivir was not associated with statistically significant clinical benefits. However, the numerical reduction in time to clinical improvement in those treated earlier requires confirmation in larger studies.FundingChinese Academy of Medical Sciences Emergency Project of COVID-19, National Key Research and Development Program of China, the Beijing Science and Technology Project.
| S-EPMC7190303 | biostudies-literature
Project description:BackgroundStaphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection.MethodsIn this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants.FindingsBetween Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005).InterpretationAdjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia.FundingUK National Institute for Health Research Health Technology Assessment.
| S-EPMC5820409 | biostudies-literature
Project description:BackgroundMemantine has been used off-label to treat frontotemporal lobar degeneration (FTD). A previous 26-week open-label study suggested a transient, modest benefit on neuropsychiatric symptoms as measured by the neuropsychiatric inventory (NPI). We aimed to determine whether memantine is an effective treatment for FTD.MethodsWe did a randomised, parallel group, double-blind, placebo-controlled trial of 20 mg memantine taken orally daily for 26 weeks in patients with FTD. Participants met Neary criteria for behavioural variant FTD (bvFTD) or semantic dementia and had characteristic brain atrophy. Use of acetylcholinesterase inhibitors was prohibited. Individuals were randomly assigned to receive either memantine or matched placebo tablets (1:1) in blocks of two and four patients. All patients and study personnel were masked to treatment assignment. Primary endpoints were the change in total NPI score and clinical global impression of change (CGIC) score after 26 weeks and were analysed by intention to treat. This study is registered with Clinicaltrials.gov, number NCT00545974.FindingsOf 100 patients screened, 81 were randomly assigned to receive memantine (39 patients) or placebo (42 patients). Five (6%) patients discontinued, and 76 completed the 26-week treatment. Enrolment numbers were lower than planned because of many patients' preference to take memantine or cholinesterase inhibitors off-label rather than participate in a clinical trial. Memantine treatment had no effect on either the NPI (mean difference 2·2, 95% CI -3·9 to 8·3, p=0·47) or CGIC (mean difference 0·0, -0·4 to 0·4, p=0·90) after 26 weeks of treatment. Memantine was generally well tolerated; however, patients in the memantine group had more frequent cognitive adverse events (six patients) than those in the placebo group (one).InterpretationMemantine treatment showed no benefit in patients with FTD. These data do not support memantine use in FTD.FundingForest Research Institute.
| S-EPMC3756890 | biostudies-literature