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Feasibility randomised multicentre, double-blind, double-dummy controlled trial of anakinra, an interleukin-1 receptor antagonist versus intramuscular methylprednisolone for acute gout attacks in patients with chronic kidney disease (ASGARD): protocol study.

ABSTRACT: INTRODUCTION:Acute gout occurs in people with chronic kidney disease, who are commonly older people with comorbidities such as hypertension, heart disease and diabetes. Potentially harmful treatments are administered to these vulnerable patients due to a lack of clear evidence. Newly available treatment that targets a key inflammatory pathway in acute gout attacks provides an opportunity to undertake the first-ever trial specifically looking treating people with kidney disease. This paper describes the protocol for a feasibility randomised controlled trial (RCT) comparing anakinra, a novel interleukin-1 antagonist versus steroids in people with chronic kidney disease (ASGARD). METHODS AND ANALYSIS:ASGARD is a two-parallel group double-blind, double-dummy multicentre RCT comparing anakinra 100 mg, an interleukin-1 antagonist, subcutaneous for 5 days against intramuscular methylprednisolone 120 mg. The primary objective is to assess the feasibility of the trial design and procedures for a definitive RCT. The specific aims are: (1) test recruitment and retention rates and willingness to be randomised; (2) test eligibility criteria; (3) collect and analyse outcome data to inform sample and power calculations for a trial of efficacy; (4) collect economic data to inform a future economic evaluation estimating costs of treatment and (5) assess capacity of the project to scale up to a national multicentre trial. We will also gather qualitative insights from participants. It aims to recruit 32 patients with a 1:1 randomisation. Information from this feasibility study will help design a definitive trial and provide general information in designing acute gout studies. ETHICS AND DISSEMINATION:The London-Central Ethics Committee approved the protocol. The results will be disseminated in peer-reviewed journals and at scientific conferences. TRIAL REGISTRATION NUMBER:EudraCT No. 2015-001787-19, NCT/Clinicalstrials.gov No. NCT02578394, pre-results, WHO Universal Trials Reference No. U1111-1175-1977. NIHR Grant PB-PG-0614-34090.

SUBMITTER: Balasubramaniam G

PROVIDER: S-EPMC5588981 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Feasibility randomised multicentre, double-blind, double-dummy controlled trial of anakinra, an interleukin-1 receptor antagonist versus intramuscular methylprednisolone for acute gout attacks in patients with chronic kidney disease (ASGARD): protocol study.

Balasubramaniam Gowrie G Parker Trisha T Turner David D Parker Mike M Scales Jonathan J Harnett Patrick P Harrison Michael M Ahmed Khalid K Bhagat Sweta S Marianayagam Thiraupathy T Pitzalis Costantino C Mallen Christian C Roddy Edward E Almond Mike M Dasgupta Bhaskar B

BMJ open 20170905 9

<h4>Introduction</h4>Acute gout occurs in people with chronic kidney disease, who are commonly older people with comorbidities such as hypertension, heart disease and diabetes. Potentially harmful treatments are administered to these vulnerable patients due to a lack of clear evidence. Newly available treatment that targets a key inflammatory pathway in acute gout attacks provides an opportunity to undertake the first-ever trial specifically looking treating people with kidney disease. This pape ...[more]

PMID: 28877949

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Project description:INTRODUCTION:Psoriasis vulgaris is a common skin disease that is characterised by persistent localised erythematous scaly plaques. Yinxieling is a Chinese herbal formula for psoriasis that has been used for more than 20 years in China. To facilitate application, PSORI-CM01 was developed based on the optimisation and simplification of Yinxieling tablets performed in a previous study and in clinical practice. However, the scientific evidence regarding whether PSORI-CM01 is more effective for psoriasis than the original Yinxieling remains insufficient. Therefore, we designed a randomised clinical trial to investigate the effect, safety and cost-effectiveness of PSORI-CM01 granules compared with those of Yinxieling tablets for the treatment of patients with psoriasis. METHODS AND ANALYSIS:This ongoing study is a two-arm parallel, randomised, double-blind, double-dummy clinical trial. Five hundred and fifty-six participants with psoriasis will be recruited and then randomly allocated into two groups in a 1:1 ratio. Participants in PSORI-CM01 group will receive a 5.5?g granule of PSORI-CM01 two times daily and five placebo tablets three times daily for 12 weeks. The participants in the Yinxieling group will receive five Yinxieling tablets three times daily and a placebo granule two times daily for 12 weeks. The primary outcome is the reduction of the Psoriasis Area and Severity Index. The secondary outcomes include relapse rate, Visual Analogue Scale scores, body surface area and the Dermatology Life Quality Index. Cost-effectiveness analysis will be performed from a health and community care provider perspective. ETHICS AND DISSEMINATION:This research protocol had been reviewed and approved by the institutional review boards of three trial centres (Guangdong Provincial Hospital of Chinese Medicine (B2014-026-01), Affiliated Hospital of Tianjin Chinese Medicine Academy (2014-KY-001) and Third Hospital of Hangzhou (B2014-026-01)). The findings will be disseminated to the public through conference presentations and open-access journals. TRIAL REGISTRATION NUMBER:Chinese Clinical Trial Registry (ChiCTR-TRC-14005185); Pre-results.

Project description:ObjectiveSeveral plausible mechanisms and anecdotal descriptions suggest that gout attacks often occur at night, although there are no scientific data supporting this. We undertook this study to evaluate the hypothesis that gout attacks occur more frequently at night.MethodsWe conducted a case-crossover study to examine the risk of acute gout attacks in relation to the time of the day. Gout patients were prospectively recruited and followed up via the internet for 1 year. Participants were asked about the following information concerning their gout attacks: the date and hour of attack onset, symptoms and signs, medication use, and purported risk factors during the 24- and 48-hour periods prior to the gout attack. We calculated the odds ratios (ORs) of gout attacks (with 95% confidence intervals [95% CIs]) according to three 8-hour time blocks of the day (i.e., 12:00 AM to 7:59 AM, 8:00 AM to 3:59 PM [reference], and 4:00 PM to 11:59 PM) using conditional logistic regression.ResultsOur study included 724 gout patients who experienced a total of 1,433 attacks (733, 310, and 390 attacks during the first, second, and third 8-hour time blocks, respectively) over 1 year. The risk of gout flares in the 8-hour overnight time block (12:00 AM to 7:59 AM) was 2.36 times higher than in the daytime (8:00 AM to 3:59 PM) (OR 2.36 [95% CI 2.05-2.73]). The corresponding OR in the evening (4:00 PM to 11:59 PM) was 1.26 (95% CI 1.07-1.48). These associations persisted among those with no alcohol use and in the lowest quintile of purine intake in the 24 hours prior to attack onset. Furthermore, these associations persisted in subgroups according to sex, age group, obesity status, diuretic use, and use of allopurinol, colchicine, and nonsteroidal antiinflammatory drugs.ConclusionThese findings provide the first prospective evidence that the risk of gout attacks during the night and early morning is 2.4 times higher than in the daytime. Further, these data support the purported mechanisms and historical descriptions of the nocturnal onset of gout attacks and may have implications for antigout prophylactic measures.

Project description:AimsTo measure and evaluate clinical response to nasal naloxone in opioid overdoses in the pre-hospital environment.DesignRandomised, controlled, double-dummy, blinded, non-inferiority trial, and conducted at two centres.SettingParticipants were included by ambulance staff in Oslo and Trondheim, Norway, and treated at the place where the overdose occurred.ParticipantsMen and women age above 18 years with miosis, rate of respiration ≤8/min, and Glasgow Coma Score <12/15 were included. Informed consent was obtained through a deferred-consent procedure.Intervention and comparatorA commercially available 1.4 mg/0.1 mL intranasal naloxone was compared with 0.8 mg/2 mL naloxone administered intramuscularly.MeasurementsThe primary end-point was restoration of spontaneous respiration of ≥10 breaths/min within 10 minutes. Secondary outcomes included time to restoration of spontaneous respiration, recurrence of overdose within 12 hours and adverse events.FindingsIn total, 201 participants were analysed in the per-protocol population. Heroin was suspected in 196 cases. With 82% of the participants being men, 105 (97.2%) in the intramuscular group and 74 (79.6%) in the intranasal group returned to adequate spontaneous respiration within 10 minutes after one dose. The estimated risk difference was 17.5% (95% CI, 8.9%-26.1%) in favour of the intramuscular group. The risk of receiving additional naloxone was 19.4% (95% CI, 9.0%-29.7%) higher in the intranasal group. Adverse reactions were evenly distributed, except for drug withdrawal reactions, where the estimated risk difference was 6.8% (95% CI, 0.2%-13%) in favour of the intranasal group in a post hoc analysis.ConclusionIntranasal naloxone (1.4 mg/0.1 mL) was less efficient than 0.8 mg intramuscular naloxone for return to spontaneous breathing within 10 minutes in overdose patients in the pre-hospital environment when compared head-to-head. Intranasal naloxone at 1.4 mg/0.1 mL restored breathing in 80% of participants after one dose and had few mild adverse reactions.

Project description:IntroductionElectronic cigarettes (EC) mainly with nicotine content are widely used worldwide. Although the number of publications about its use is increasing exponentially, evidence-based, unbiased, conclusive, head-to-head comparisons about its efficacy and safety as an aid for smoking cessation are lacking. METHODS AND ANALYSIS: Design: randomised, placebo and reference treatment-controlled, multicentre, double-blind, double-dummy, parallel-group trial. Participants: smokers smoking at least 10 cigarettes/day in the past year and motivated to quit, aged 18-70 years. Interventions: (A) EC without nicotine (ECwoN) plus placebo tablets of varenicline administered by oral route: placebo condition, (B) EC with nicotine (ECwN) plus placebo tablets of varenicline: ECwN condition. Voltage regulated EC will be used with liquid containing 12 mg/mL of nicotine for ad libitum use. Flavour: blond tobacco. (C) Reference: ECwoN plus 0.5 mg varenicline tablets: varenicline condition. Varenicline administered according to the marketing authorisationauthorisation. Treatment duration: 1 week+3 months. Primary outcome: continuous smoking abstinence rate (CAR) (abstinence from conventional/combustible cigarettes) during the last 4 weeks (weeks 9-12) of the treatment period defined as self-report of no smoking during the previous 2 weeks and expired air carbon monoxide ≤8 at visit 4 at week 10 after target quit date (TQD), that is, 11 weeks after treatment initiation AND at visit 5, week 12 after TQD, that is, 13 weeks after treatment initiation. Secondary outcomes: safety profile; point prevalence abstinence rate; CAR confirmed by urinary anabasine concentration; changes in cigarettes/day consumption; craving for tobacco and withdrawal symptoms with respect of baseline.Ethics and disseminationThe ethics committee approval was obtained on 17 April 2018. All data collected about the study participants will be anonymised. Investigators will communicate trial results to participants, health authorities, healthcare professionals, the public and other relevant groups without any publication restrictions.Trial registration numberNCT03630614; Pre-results.

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Feasibility randomised multicentre, double-blind, double-dummy controlled trial of anakinra, an interleukin-1 receptor antagonist versus intramuscular methylprednisolone for acute gout attacks in patients with chronic kidney disease (ASGARD): protocol study.

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Feasibility randomised multicentre, double-blind, double-dummy controlled trial of anakinra, an interleukin-1 receptor antagonist versus intramuscular methylprednisolone for acute gout attacks in patients with chronic kidney disease (ASGARD): protocol study.

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