11 results found
Fiorentino F, 2021, Feasibility of Comparative Health Research Outcome of Novel Surgery in prostate cancer (IP4-CHRONOS): statistical analysis plan for the randomised feasibility phase of the CHRONOS study., Trials, Vol: 22, Pages: 1-12, ISSN: 1745-6215
BackgroundRandomised controlled trials (RCTs) for surgical interventions have often proven difficult with calls for innovative approaches. The Imperial Prostate (IP4) Comparative Health Research Outcomes of Novel Surgery in prostate cancer (IP4-CHRONOS) study aims to deliver level 1 evidence on outcomes following focal therapy which involves treating just the tumour rather than whole-gland surgery or radiotherapy. Our aim is to test the feasibility of two parallel RCTs within an overarching strategy that fits with existing patient and physician equipoise and maximises the chances of success and potential benefit to patients and healthcare services.Methods and designIP4-CHRONOS is a randomised, unblinded multi-centre study, including two parallel randomised controlled trials targeting the same patient population: IP4-CHRONOS-A and IP4-CHRONOS-B.IP4-CHRONOS-A is a 1:1 RCT and the other is a multi-arm, multi-stage (MAMS) RCT starting with three arms and a 1:1:1 randomisation. The two linked RCTs are discussed with patients at the time of consent and the choice of A or B is dependent on physician and patient equipoise. The primary outcome is the feasibility of recruitment, acceptance of randomisation and compliance to allocated arm.ResultsThis paper describes the statistical analysis plan (SAP) for the feasibility study within IP4-CHRONOS given its innovative approach. Version 1.0 of the SAP has been reviewed by the Trial Steering Committee (TSC), Chief Investigator (CI), Senior Statistician and Trial Statistician and signed off. The study is ongoing and recruiting. Recruitment is scheduled to finish later in 2021. The SAP documents approved methods and analyses that will be conducted. Since this is written in advance of the analysis, we avoid bias arising from prior knowledge of the study data and findings.DiscussionOur feasibility analysis will demonstrate if IP4-CHRONOS is feasible in terms of recruitment, randomisation and compliance, and whether to continue both A
Bass EJ, Klimowska-Nassar N, Sasikaran T, et al., 2021, PROState pathway embedded comparative trial: the IP3-PROSPECT study, Contemporary Clinical Trials, Vol: 107, ISSN: 1551-7144
IntroductionThe traditional double blind RCT is the ‘gold standard’ trial design. For a variety of reasons, these designs often fail to accrue enough participants to conclude. This is particularly challenging in localized prostate cancer. The cohort multiple randomised controlled trial (cmRCT) trial design may represent an alternative approach to delivering robust comparative data in prostate cancer.Patients and methodsIP3-PROSPECT is a cmRCT designed to test multiple prostate cancer interventions from eligible men in one cohort. Key to the design is two points of consent. First, at point of consent one, men referred for prostate cancer investigations are invited to join the cohort. They may then be randomly invited at a later date to consider an intervention at point of consent two. In the pilot phase we will test the acceptability and feasibility of developing the cohort.ResultsAcceptability and feasibility of the study will be measured by a combination of quantitative and qualitative methods. The primary outcome measure is the rate of consent to inclusion to the IP3-PROSPECT cohort. Secondary outcome measures include the completeness of data collection at sites and return rates of patient questionnaires. We will also interview patients and healthcare professionals to explore their thoughts on the implementation, practicality and efficiency of IP3-PROSPECT.ConclusionThe IP3-PROSPECT study will evaluate the cmRCT design in prostate cancer. Initially we will pilot the design, assessing for acceptability and feasibility. The cmRCT is an innovative design that offers potential for building a modern comparative evidence base for prostate cancer.
Lyon A, Babalis D, Morley-Smith AC, et al., 2020, Investigation of the safety and feasibility of AAV1/SERCA2a gene transfer in patients with chronic heart failure supported with a left ventricular assist device – the SERCA-LVAD TRIAL, Gene Therapy, Vol: 27, Pages: 579-590, ISSN: 0969-7128
The SERCA-LVAD trial was a phase 2a trial assessing the safety and feasibility of delivering an adeno-associated vector 1 carrying the cardiac isoform of the sarcoplasmic reticulum calcium ATPase (AAV1/SERCA2a) to adult chronic heart failure patients implanted with a left ventricular assist device. Enrolled subjects were randomised to receive a single intracoronary infusion of 1x1013 DNase-resistant AAV1/SERCA2a particles or a placebo solution in a double-blinded design, stratified by presence of neutralising antibodies to AAV. Elective endomyocardial biopsy was performed at 6 months unless the subject had undergone cardiac transplantation, with myocardial samples assessed for the presence of exogenous viral DNA from the treatment vector. Safety assessments including ELISPOT were serially performed. Although designed as a 24 subject trial, recruitment was stopped after five subjects had been randomised and received infusion due to the neutral result from the CUPID 2 trial. Here we describe the results from the 5 patients, which confirmed that viral DNA was delivered to the failing human heart in 2 patients receiving gene therapy with vector detectable at follow up endomyocardial biopsy or cardiac transplantation. Absolute levels of detectable transgene DNA were low, and no functional benefit was observed. There were no safety concerns in this small cohort. This trial identified some of the challenges of performing gene therapy trials in this LVAD patient cohort, which may help guide future trial design.
Sasikaran T, Johnson N, 2020, Daycase Cryo-balloon Ablation Without Pulmonary Vein Mapping Versus A Conventional Cryo-balloon Approach: Quality Of Life Results From The Prospective, Randomised, Multi-Center AVATAR-AF Trial, 2020 Heart Rhythm Society Scientific Session
Johnson NA, Sasikaran T, 2019, AVATAR-AF: Getting to the heart of data management for analysis (5 simple rules to follow to ensure data integrity), 5th International Clinical Trials Methodology Conference, Publisher: BMC
Mann I, Sasikaran T, Sandler B, et al., 2019, Ablation versus anti-arrhythmic therapy for reducing all hospital episodes from recurrent atrial fibrillation (AVATAR-AF): design and rationale, American Heart Journal, Vol: 214, Pages: 36-45, ISSN: 0002-8703
Atrial Fibrillation (AF) ablation using the cryoballoon is effective at reducing symptomatic AF episodes. The prevalence of AF is increasing with the aging population and access to such treatment would be enhanced by reducing the resource requirements. Relinquishing electrical mapping of the pulmonary veins (PV) removes the need for PV catheters, electrical recording equipment and staff trained in using this equipment. Moreover, the majority of complications are peri-procedural so overnight hospitalization maybe unnecessary. We tested this streamlined approach to AF ablation against medical therapy using the endpoint of time to all hospital episodes. METHODS: The AVATAR-AF study is a prospective, multicenter, randomized controlled trial testing the primary hypothesis that AF ablation done without PV mapping or overnight hospitalization is more effective than anti-arrhythmic drugs at reducing all hospital episodes related to recurrent atrial arrhythmias. We included a third arm to test a secondary hypothesis that confirming PV entrance block as per consensus guidelines can improve outcomes. Three hundred twenty-one patients with documented paroxysmal AF will be randomized in a 1:1:1 manner to one of three investigation arms: (1) AVATAR protocol cryoballoon ablation without assessment of acute PV isolation or overnight hospitalization; (2) medical therapy with anti-arrhythmic drugs; or (3) conventional cryoballoon ablation with assessment of acute PV isolation. The primary endpoint is defined as the time to all hospital episodes (including outpatient consultation) related to treatment for atrial arrhythmia. CONCLUSION: The AVATAR-AF study will determine whether the resource utilization for AF ablation can be reduced whilst maintaining superiority over medical therapy.
Khan JN, Nazir SA, Greenwood JP, et al., 2016, Infarct size following complete revascularization in patients presenting with STEMI: a comparison of immediate and staged in-hospital non-infarct related artery PCI subgroups in the CvLPRIT study, Journal of Cardiovascular Magnetic Resonance, Vol: 18, Pages: 1-9, ISSN: 1097-6647
BackgroundThe CvLPRIT study showed a trend for improved clinical outcomes in the complete revascularisation (CR) group in those treated with an immediate, as opposed to staged in-hospital approach in patients with multivessel coronary disease undergoing primary percutaneous intervention (PPCI). We aimed to assess infarct size and left ventricular function in patients undergoing immediate compared with staged CR for multivessel disease at PPCI.MethodsThe Cardiovascular Magnetic Resonance (CMR) substudy of CvLPRIT was a multicentre, prospective, randomized, open label, blinded endpoint trial in PPCI patients with multivessel disease. These data refer to a post-hoc analysis in 93 patients randomized to the CR arm (63 immediate, 30 staged) who completed a pre-discharge CMR scan (median 2 and 4 days respectively) after PPCI. The decision to stage non-IRA revascularization was at the discretion of the treating interventional cardiologist.ResultsPatients treated with a staged approach had more visible thrombus (26/30 vs. 31/62, p = 0.001), higher SYNTAX score in the IRA (9.5, 8–16 vs. 8.0, 5.5–11, p = 0.04) and a greater incidence of no-reflow (23.3 % vs. 1.6 % p < 0.001) than those treated with immediate CR. After adjustment for confounders, staged patients had larger infarct size (19.7 % [11.7–37.6] vs. 11.6 % [6.8–18.2] of LV Mass, p = 0.012) and lower ejection fraction (42.2 ± 10 % vs. 47.4 ± 9 %, p = 0.019) compared with immediate CR.ConclusionsOf patients randomized to CR in the CMR substudy of CvLPRIT, those in whom the operator chose to stage revascularization had larger infarct size and lower ejection fraction, which persisted after adjusting for important covariates than those who underwent immediate CR. Prospective randomized trials are needed to assess whether immediate CR results in better clinical outcomes than staged CR.T
McCann GP, Khan JN, Greenwood JP, et al., 2015, Complete Versus Lesion-Only Primary PCI The Randomized Cardiovascular MR CvLPRIT Substudy, JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, Vol: 66, Pages: 2713-2724, ISSN: 0735-1097
Gershlick AH, Khan JN, Kelly DJ, et al., 2015, REPLY: Complete Revascularization in Patients Undergoing Primary Percutaneous Coronary Intervention for STEMI Is It Really What We Should Be Doing?, JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, Vol: 66, Pages: 332-333, ISSN: 0735-1097
Gershlick AH, Khan JN, Kelly DJ, et al., 2015, Randomized Trial of Complete Versus Lesion-Only Revascularization in Patients Undergoing Primary Percutaneous Coronary Intervention for STEMI and Multivessel Disease, JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, Vol: 65, Pages: 963-972, ISSN: 0735-1097
Rodgers A, Patel A, Berwanger O, et al., 2011, An International Randomised Placebo-Controlled Trial of a Four-Component Combination Pill ("Polypill") in People with Raised Cardiovascular Risk, PLOS One, Vol: 6, ISSN: 1932-6203
Background: There has been widespread interest in the potential of combination cardiovascular medications containingaspirin and agents to lower blood pressure and cholesterol (‘polypills’) to reduce cardiovascular disease. However, noreliable placebo-controlled data are available on both efficacy and tolerability.Methods: We conducted a randomised, double-blind placebo-controlled trial of a polypill (containing aspirin 75 mg,lisinopril 10 mg, hydrochlorothiazide 12.5 mg and simvastatin 20 mg) in 378 individuals without an indication for anycomponent of the polypill, but who had an estimated 5-year cardiovascular disease risk over 7.5%. The primary outcomeswere systolic blood pressure (SBP), LDL-cholesterol and tolerability (proportion discontinued randomised therapy) at 12weeks follow-up.Findings: At baseline, mean BP was 134/81 mmHg and mean LDL-cholesterol was 3.7 mmol/L. Over 12 weeks, polypilltreatment reduced SBP by 9.9 (95% CI: 7.7 to 12.1) mmHg and LDL-cholesterol by 0.8 (95% CI 0.6 to 0.9) mmol/L. Thediscontinuation rates in the polypill group compared to placebo were 23% vs 18% (RR 1.33, 95% CI 0.89 to 2.00, p = 0.2).There was an excess of side effects known to the component medicines (58% vs 42%, p = 0.001), which was mostly apparentwithin a few weeks, and usually did not warrant cessation of trial treatment.Conclusions: This polypill achieved sizeable reductions in SBP and LDL-cholesterol but caused side effects in about 1 in 6people. The halving in predicted cardiovascular risk is moderately lower than previous estimates and the side effect rate ismoderately higher. Nonetheless, substantial net benefits would be expected among patients at high risk.
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.