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Trial summary and protocol for a phase II randomised placebo-controlled double-blinded trial of Interleukin 1 blockade in Acute Severe Colitis: the IASO trial.

ABSTRACT: INTRODUCTION:Acute severe ulcerative colitis (ASUC) is a severe manifestation of ulcerative colitis (UC) that warrants hospitalisation. Despite significant advances in therapeutic options for UC and in the medical management of steroid-refractory ASUC, the initial treatment paradigm has not changed since 1955 and is based on the use of intravenous corticosteroids. This treatment is successful in approximately 50% of patients but failure of this and subsequent medical therapy still occurs, with colectomy rates of up to 40% reported. The Interleukin 1 (IL-1) blockade in Acute Severe Colitis (IASO) trial aims to investigate whether antagonism of IL-1 signalling using anakinra in addition to intravenous corticosteroid treatment can improve outcomes in patients with ASUC. METHODS AND ANALYSIS:IASO is a phase II, multicentre, two-arm (parallel group), randomised (1:1), placebo-controlled, double-blinded trial of short-duration anakinra in ASUC. Its primary outcome will be the incidence of medical (eg, infliximab/ciclosporin) or surgical rescue therapy (colectomy) within 10 days following the commencement of intravenous corticosteroid therapy. Secondary outcomes will include disease activity, time to clinical response, time to rescue therapy, colectomy incidence by day 98 post intravenous corticosteroids and safety. The trial aims to recruit 214 patients across 20 sites in the UK. ETHICS AND DISSEMINATION:The trial has received approval from the Cambridge Central Research Ethics Committee (Ref: 17/EE/0347), the Health Research Authority (Ref: 201505) and Clinical Trials Authorisation from the Medicines and Healthcare products Regulatory Agency. We plan to present trial findings at scientific conferences and publish in high-impact peer-reviewed journals. TRIAL REGISTRATION NUMBER:ISRCTN43717130; EudraCT 2017-001389-10.

SUBMITTER: Thomas MG

PROVIDER: S-EPMC6398753 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Trial summary and protocol for a phase II randomised placebo-controlled double-blinded trial of Interleukin 1 blockade in Acute Severe Colitis: the IASO trial.

Thomas Martin Geoffrey MG Bayliss Carrie C Bond Simon S Dowling Francis F Galea James J Jairath Vipul V Lamb Christopher C Probert Christopher C Timperley-Preece Elizabeth E Watson Alastair A Whitehead Lynne L Williams John G JG Parkes Miles M Kaser Arthur A Raine Tim T

BMJ open 20190215 2

<h4>Introduction</h4>Acute severe ulcerative colitis (ASUC) is a severe manifestation of ulcerative colitis (UC) that warrants hospitalisation. Despite significant advances in therapeutic options for UC and in the medical management of steroid-refractory ASUC, the initial treatment paradigm has not changed since 1955 and is based on the use of intravenous corticosteroids. This treatment is successful in approximately 50% of patients but failure of this and subsequent medical therapy still occurs ...[more]

PMID: 30772849

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Project description:INTRODUCTION:Postcraniotomy pain protocols use opioids, which are considered suboptimal analgesia following this procedure. Multimodal analgesia components are sparse. Our null hypothesis states that sumatriptan is not different to placebo in addition to usual intravenous opioids, for the treatment of acute postcraniotomy pain. METHODS AND ANALYSIS:This is a prospective single-centre randomised double-blinded placebo-controlled phase III clinical trial comparing subcutaneous sumatriptan injection in the recovery area with placebo for the treatment of postcraniotomy pain. Eligible adult patients (18 years and older) undergoing craniotomy will be identified preoperatively. Both patient groups will receive a subcutaneous injection at a point where recovery-nursing staff would initiate the usual intravenous opioid analgesia as per standardised pain management protocol. In both groups, further pain management will be followed by the usual intravenous opioid administration. Primary outcome will consist of the difference in pain experienced by the two groups of patients in recovery area 60?min after the study drug administration. Postcraniotomy pain will be measured at regular intervals using the Visual Analogue Scale (VAS) in recovery area. The minimal clinically important difference of 10?mm on the VAS between the two groups will be considered as statistically significant. We will include selected clinical and patient-reported outcomes as secondary endpoints. Univariate regression will be conducted on each one of the clinically plausible potential confounders. We will enrol a total 136 patients, with the study duration of 2 years. This trial will commence recruitment on the 1 July 2019. ETHICS AND DISSEMINATION:This trial protocol has achieved approval by the Austin Health Research Committee, HREC/17/Austin/596. This trial was prospectively registered with Australian New Zealand Clinical Trials Registry on the 10/05/2018 with a unique trial identifier U1111-1209-9072 and registration Number ACTRN12618000793213P. Findings of this study will be disseminated in peer-reviewed academic journals. TRIAL REGISTRATION NUMBER:U1111-1209-9072, ACTRN12618000793213P.

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Project description:BackgroundAndrogenetic alopecia (AGA) is the most common hair loss disorder seen in men. It can have an early onset but has also been associated with ageing and senescence. It often induces pronounced psychological impact. ALRV5XR, a new hair loss treatment herein evaluated, was designed to target multiple molecular pathways involved in hair growth and hair follicle stem cell biology. The main objectives of the study were the assessment of safety and efficacy profiles of ALRV5XR in men.MethodsThis 24-week, parallel randomised, placebo-controlled, double-blinded clinical trial was performed in a USA community clinic. Healthy men (age 22-65) with AGA and belonging to the Hamilton-Norwood (HN) classification I-VII and Fitzpatrick skin type (FST) I-VI, were randomly allocated in a 1:1 ratio into ALRV5XR or placebo treatment groups. Dermatologist assessment, phototrichograms, and blood samples were obtained in a blinded fashion at baseline, 12 and 24 weeks. Subjects were given a masked treatment consisting of oral capsules, shampoo, conditioner, and follicle serum, which was intended for daily use. Efficacy was assessed via absolute and per cent changes in terminal hair (TH) density, and response rates. The trial was registered with clinicaltrials.gov (NCT04450589) and is completed.FindingsForty-six subjects were enroled in the study, 23 allocated to the ALRV5XR treatment and 23 to the placebo group. Enrolment occurred from April 11 to October 23, 2018. Thirty-six subjects completed the trial (17 ALRV5XR, 19 placebo) and 11 subjects in each group were evaluable for TH outcomes. At 24 weeks, the absolute change in TH density improved by 21·0 THs/cm2 (95% CI: 9·2-32·8; p = 0·0014), and the relative density increased by 16·4% (95% CI: 7·4%-25·5%; p = 0·0012). The odds ratio for being a responder (≥ 0 change) was 87·4. TH density increased linearly and was not affected by HN, FST, ethnicity, age, or body mass index. All subjects in the ALRV5XR group responded to treatment while 81·8% of the placebo group decreased TH density. ALRV5XR induced statistically significant changes in both decrease in vellus hair (VH) density as well as in concomitant increase of the TH/VH ratio when compared to placebo. ALRV5XR was well tolerated, and no adverse events were observed.InterpretationALRV5XR treatment resulted in clinically significant TH regrowth in men with AGA. Furthermore, it appeared to reverse the characteristic hair miniaturisation seen in this condition. When compared to results of published trials of standard therapy, ALRV5XR showed a multi-fold increase both in efficacy and in response rates. In addition, the continuance of TH regrowth from 12 to 24 weeks suggests that the normal structure and function of non-productive telogen follicles is restored and that a normal hair phenotype may be attained by extended ALRV5XR treatment.FundingArbor Life Labs.

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Trial summary and protocol for a phase II randomised placebo-controlled double-blinded trial of Interleukin 1 blockade in Acute Severe Colitis: the IASO trial.

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Trial summary and protocol for a phase II randomised placebo-controlled double-blinded trial of Interleukin 1 blockade in Acute Severe Colitis: the IASO trial.

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