scholarly journals An evaluation of the effect of an angiotensin-converting enzyme inhibitor on the growth rate of small abdominal aortic aneurysms: a randomised placebo-controlled trial (AARDVARK)

2016 ◽  
Vol 20 (59) ◽  
pp. 1-180 ◽  
Author(s):  
Gaia Kiru ◽  
Colin Bicknell ◽  
Emanuela Falaschetti ◽  
Janet Powell ◽  
Neil Poulter ◽  
...  
Keyword(s):  
Growth Rate ◽  
Adverse Events ◽  
Angiotensin Converting Enzyme ◽  
Technology Assessment ◽  
Growth Rates ◽  
Controlled Trial ◽  
Health Technology ◽  
Diameter Growth ◽  
Converting Enzyme ◽  
Abdominal Aortic

BackgroundAlthough data are inconsistent, angiotensin-converting enzyme inhibitors (ACE-Is) have been associated with a reduced incidence of abdominal aortic aneurysm (AAA) rupture in analysis of administrative databases.Objectives(1) To investigate whether or not the ACE-I perindopril (Coversyl arginine, Servier) reduces small AAA growth rate and (2) to evaluate blood pressure (BP)-independent effects of perindopril on small AAA growth and to compare the repeatability of measurement of internal and external aneurysm diameters.DesignA three-arm, multicentre, single-blind, randomised placebo-controlled trial.SettingFourteen hospitals in England.ParticipantsMen or women aged ≥ 55 years with an AAA of 3.0–5.4 cm in diameter by internal or external measurement according to ultrasonography and who met the trial eligibility criteria.InterventionsPatients were randomised to receive 10 mg of perindopril arginine daily, 5 mg of the calcium channel blocker amlodipine daily or placebo daily.Main outcome measuresThe primary outcome was AAA diameter growth using external measurements in the longitudinal plane, which in-trial studies suggested was the preferred measure. Secondary outcome measures included AAA rupture, AAA repair, modelling of the time taken for the AAA to reach the threshold for intervention (5.5 cm) or referral for surgery, tolerance of study medication (measured by compliance, adverse events and quality of life) and a comparison of the repeatability of measures of internal and external AAA diameter. Patients were followed up every 3–6 months over 2 years.ResultsIn total, 227 patients were recruited and randomised into the three groups, which were generally well matched at baseline. Multilevel modelling was used to determine the maximum likelihood estimates for AAA diameter growth. No significant differences in the estimates of annual growth were apparent [1.68 (standard error 0.02) mm, 1.77 (0.02) mm and 1.81 (0.02) mm in the placebo, perindopril and amlodipine groups, respectively]. Similarly, no significant differences in the slopes of modelled growth over time were apparent between perindopril and placebo (p = 0.78) or between perindopril and amlodipine (p = 0.89). The results were essentially unaffected by adjustment for potential confounders. Compliance, measured by pill counts, was good throughout (> 80% at all visit time points). There were no significant in-trial safety concerns. Six patients withdrew because of adverse events attributed to the study medications (n = 2 perindopril,n = 4 amlodipine). No patients ruptured their AAA and 27 underwent elective surgery during the trial (n = 9 placebo,n = 10 perindopril,n = 8 amlodipine).ConclusionsWe were unable to demonstrate a significant impact of perindopril compared with placebo or amlodipine on small AAA growth over a 2-year period. Furthermore, there were no differences in the times to reach a diameter of 5.5 cm or undergo surgery among the three groups. Perindopril and amlodipine were well tolerated by this population. External AAA measurements were found to be more repeatable than internal measurements. The observed AAA growth measurement variability was greater than that expected pre trial. This, combined with slower than expected mean growth rates, resulted in our having limited power to detect small differences between growth rates and hence this adds uncertainty to the interpretation of the results. Several further analyses are planned including a multivariate analysis of determinants of AAA growth, an evaluation of the possible differential effect of perindopril on fast AAA growth and an investigation into the roles of central BP and BP variability on AAA growth.Trial registrationCurrent Controlled Trials ISRCTN51383267.FundingThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 20, No. 59. See the NIHR Journals Library website for further project information. The NIHR Biomedical Research Centre based at Imperial College NHS Trust supported the trial. Servier provided perindopril at no charge.

scholarly journals Saline in Acute Bronchiolitis RCT and Economic evaluation: hypertonic saline in acute bronchiolitis – randomised controlled trial and systematic review

2015 ◽  
Vol 19 (66) ◽  
pp. 1-130 ◽  
Author(s):  
Mark L Everard ◽  
Daniel Hind ◽  
Kelechi Ugonna ◽  
Jennifer Freeman ◽  
Mike Bradburn ◽  
...  
Keyword(s):  
Systematic Review ◽  
Randomised Controlled Trial ◽  
Adverse Events ◽  
Supportive Care ◽  
Technology Assessment ◽  
Controlled Trial ◽  
Health Technology ◽  
Controlled Trials ◽  
Acute Bronchiolitis ◽  
Randomised Controlled

BackgroundAcute bronchiolitis is the most common cause of hospitalisation in infancy. Supportive care and oxygen are the cornerstones of management. A Cochrane review concluded that the use of nebulised 3% hypertonic saline (HS) may significantly reduce the duration of hospitalisation.ObjectiveTo test the hypothesis that HS reduces the time to when infants were assessed as being fit for discharge, defined as in air with saturations of > 92% for 6 hours, by 25%.DesignParallel-group, pragmatic randomised controlled trial, cost–utility analysis and systematic review.SettingTen UK hospitals.ParticipantsInfants with acute bronchiolitis requiring oxygen therapy were allocated within 4 hours of admission.InterventionsSupportive care with oxygen as required, minimal handling and fluid administration as appropriate to the severity of the disease, 3% nebulised HS every ± 6 hours.Main outcome measuresThe trial primary outcome was time until the infant met objective discharge criteria. Secondary end points included time to discharge and adverse events. The costs analysed related to length of stay (LoS), readmissions, nebulised saline and other NHS resource use. Quality-adjusted life-years (QALYs) were estimated using an existing utility decrement derived for hospitalisation in children, together with the time spent in hospital in the trial.Data sourcesWe searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and other databases from inception or from 2010 onwards, searched ClinicalTrials.gov and other registries and hand-searchedChest,PaediatricsandJournal of Paediatricsto January 2015.Review methodsWe included randomised/quasi-randomised trials which compared HS versus saline (± adjunct treatment) or no treatment. We used a fixed-effects model to combine mean differences for LoS and assessed statistical heterogeneity using theI2statistic.ResultsThe trial randomised 158 infants to HS (n = 141 analysed) and 159 to standard care (n = 149 analysed). There was no difference between the two arms in the time to being declared fit for discharge [median 76.6 vs. 75.9 hours, hazard ratio (HR) 0.95, 95% confidence interval (CI) 0.75 to 1.20] or to actual discharge (median 88.5 vs. 88.7 hours, HR 0.97, 95% CI 0.76 to 1.23). There was no difference in adverse events. One infant developed bradycardia with desaturation associated with HS. Mean hospital costs were £2595 and £2727 for the control and intervention groups, respectively (p = 0.657). Incremental QALYs were 0.0000175 (p = 0.757). An incremental cost-effectiveness ratio of £7.6M per QALY gained was not appreciably altered by sensitivity analyses. The systematic review comprised 15 trials (n = 1922) including our own. HS reduced the mean LoS by –0.36 days (95% CI –0.50 to –0.22 days). High levels of heterogeneity (I2 = 78%) indicate that the result should be treated cautiously.ConclusionsIn this trial, HS had no clinical benefit on LoS or readiness for discharge and was not a cost-effective treatment for acute bronchiolitis. Claims that HS achieves small reductions in LoS must be treated with scepticism.Future workWell-powered randomised controlled trials of high-flow oxygen are needed.Study registrationThis study is registered as NCT01469845 and CRD42014007569.Funding detailsThis project was funded by the NIHR Health Technology Assessment (HTA) programme and will be published in full inHealth Technology Assessment; Vol. 19, No. 66. See the HTA programme website for further project information.

Abstract 13513: Serial CT Surveillance of Abdominal Aortic Aneurysm Diameter Demonstrates Predominantly Linear Growth (N-TA 3 CT)

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Sydney Olson ◽  
Marniker Wijesinha ◽  
Annalise Panthofer ◽  
William Blackwelder ◽  
Gilbert R Upchurch ◽  
...  
Keyword(s):  
Growth Rate ◽  
Growth Rates ◽  
Linear Growth ◽  
Growth Patterns ◽  
Aortic Aneurysms ◽  
Transverse Diameter ◽  
Invasive Treatment ◽  
Abdominal Aortic ◽  
Risk Of Rupture ◽  
Serial Ct

Objective: Small abdominal aortic aneurysms (AAAs) have a low risk of rupture. Intervention is indicated when diameters exceed established thresholds. This study assessed the growth rates and patterns of AAAs over 2 years as documented on serial CT scans from the Non-Invasive Treatment of AAA Clinical Trial. Methods: 254 patients, 35 females with baseline AAA maximum transverse diameter (MTD) between 3.5-4.5 cm and 219 males with baseline MTD 3.5-5.0 cm, were included in this study. Linear regressions and segmental growth rates were used to model growth rates and patterns. Results: The yearly growth rates of AAA MTDs had a median of 0.17 cm/yr and mean of 0.19 cm/yr ± 0.14 (Figure 1). 10% of AAA displayed minimal to no growth (< 0.05 cm/yr), 62% low growth (0.05-0.25 cm/yr), 28% high growth (> 0.25 cm/yr). Baseline AAA diameter accounted for only 5.4% of growth rate variance (P<0.001, R 2 0.05). Most AAAs displayed linear growth (70%); large variations in interval growth rates occurred infrequently (3% staccato growth, 4% exponential growth); a minority of subjects’ growth patterns were not clearly classifiable (11% indeterminate-not growing, 12% indeterminate-growing) (Figure 2). No patients with baseline MTD < 4.25 cm exceeded sex-specific repair thresholds (males 0 / 92, [95% CI, 0.00-0.06]; females 0 / 25 [95% CI, 0.00-0.25]) in the course of follow-up for as long as two years. Conclusions: The majority of small AAAs exhibit linear growth; large intra-patient growth rate variations were infrequently observed over 2 years. AAA < 4.25 cm can be followed with a CT scan in 2 years with little chance of exceeding interventional MTD thresholds of 5.5 cm for men.

The Alberta hip and knee replacement project: A model for health technology assessment based on comparative effectiveness of clinical pathways

2009 ◽  
Vol 25 (02) ◽  
pp. 113-123 ◽  
Author(s):  
Katherine L. Gooch ◽  
Douglas Smith ◽  
Tracy Wasylak ◽  
Peter D. Faris ◽  
Deborah A. Marshall ◽  
...  
Keyword(s):  
Health Technology Assessment ◽  
Knee Replacement ◽  
Study Design ◽  
Technology Assessment ◽  
Comparative Effectiveness ◽  
Clinical Pathways ◽  
Controlled Trial ◽  
Health Technology ◽  
Randomized Controlled

Background:The Alberta Hip and Knee Replacement Project developed a new evidence-based clinical pathway (NCP) for total hip (THR) and knee (TKR) replacement. The aim was to facilitate the delivery of services in a timely and cost-effective manner while achieving the highest quality of care for the patient across the full continuum of care from patient referral to an orthopedic surgeon through surgery, recovery, and rehabilitation. The purpose of this article is to provide an overview of the study design, rationale, and execution of this project as a model for health technology assessment based on comparative effectiveness of alternative clinical pathways.Methods:A pragmatic randomized controlled trial study design was used to evaluate the NCP compared with the standard of care (SOC) for these procedures. The pragmatic study design was selected as a rigorous approach to produce high quality evidence suitable for informing decisions between relevant interventions in real clinical practice. The NCP was evaluated in three of the nine regional health authorities (RHAs) in Alberta with dedicated central intake clinics offering multidisciplinary care teams, constituting 80 percent of THR and TKR surgeries performed annually in Alberta. Patients were identified in the offices of twenty orthopedic surgeons who routinely performed THR or TKR surgeries. Evaluation outcome measures were based on the six dimensions of the Alberta Quality Matrix for Health (AQMH): acceptability, accessibility, appropriateness, effectiveness, efficiency and safety. Data were collected prospectively through patient self-completed questionnaires at baseline and 3 and 12 months after surgery, ambulatory and inpatient chart reviews, and electronic administrative data.Results:The trial design was successful in establishing similar groups for rigorous evaluation. Of the 4,985 patients invited to participate, 69 percent of patients consented. A total of 3,434 patients were randomized: 1,712 to SOC and 1,722 to the NCP. The baseline characteristics of patients in the two study arms, including demographics, comorbidity as measured by CDS and exposure to pain medications, and health-related quality of life, as measured by Western Ontario and McMaster Universities Osteoarthritis Index and Short Form-36, were similar.Conclusions:The Alberta Hip and Knee Replacement Project demonstrates the feasibility and advantages of applying a pragmatic randomized controlled trial to ascertain comparative effectiveness. This is a model for health technology assessment that incorporates how clinical pathways can be effectively evaluated.

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