Conventional versus automated measurement of blood pressure in primary care patients with systolic hypertension: randomised parallel design controlled trial

Objective To compare the quality and accuracy of manual office blood pressure and automated office blood pressure using the awake ambulatory blood pressure as a gold standard

Baseline characteristics and enrichment results from the SONAR trial

Aim: The SONAR trial uses an enrichment design based on the individual response to the selective endothelin receptor antagonist atrasentan on efficacy (the degree of the individual response in the urinary albumin‐to‐creatinine ratio [UACR]) and safety/tolerability (signs of sodium retention and acute increases in serum creatinine) to assess the effects of this agent on major renal outcomes. The patient population and enrichment results are described here. Methods: Patients with type 2 diabetes with an estimated glomerular filtration rate (eGFR) within 25 to 75 mL/min/1.73 m2 and UACR between 300 and 5000 mg/g were enrolled. After a run‐in period, eligible patients received 0.75 mg/d of atrasentan for 6 weeks. A total of 2648 responder patients in whom UACR decreased by ≥30% compared to baseline were enrolled, as were 1020 non‐responders with a UACR decrease of <30%. Patients who experienced a weight gain of >3 kg and in whom brain natriuretic peptide exceeded ≥300 pg/mL, or who experienced an increase in serum creatinine >20% (0.5 mg/dL), were not randomized. Results: Baseline characteristics were similar for atrasentan responders and non‐responders. Upon entry to the study, median UACR was 802 mg/g in responders and 920 mg/g in non‐responders. After 6 weeks of treatment with atrasentan, the UACR change in responders was −48.8% (95% CI, −49.8% to −47.9%) and in non‐responders was −1.2% (95% CI, −6.4% to 3.9%). Changes in other renal risk markers were similar between responders and non‐responders except for a marginally greater reduction in systolic blood pressure and eGFR in responders. Conclusions: The enrichment period has successfully identified a population with a profound UACR reduction without clinical signs of sodium retention in whom a large atrasentan effect on clinically important renal outcomes is possible. The SONAR trial aims to establish whether atrasentan confers renal protection

Hypertension in Canada: Past, Present, and Future

Canada has an extremely successful hypertension detection and treatment program. The aim of this review was to highlight the historic and current infrastructure and initiatives that have led to this success, and the outlook moving forward into the future. We discuss the evolution of hypertension awareness and control in Canada; contributions made by organizations such as the Canadian Hypertension Society, Blood Pressure Canada, and the Canadian Hypertension Education Program; the amalgamation of these organizations into Hypertension Canada; and the impact that Hypertension Canada has had on hypertension care in Canada. The important contribution that public policy and advocacy can have on prevention and control of blood pressure in Canada is described. We also highlight the importance of population-based strategies, health care access and organization, and accurate blood pressure measurement (including ambulatory, home, and automated office modalities) in optimizing hypertension prevention and management. We end by discussing how Hypertension Canada will move forward in the near and longer term to address the unmet residual risk attributable to hypertension and associated cardiovascular risk factors. Hypertension Canada will continue to strive to enhance hypertension prevention and control rates, thereby improving the quality of life and cardiovascular outcomes of Canadians, while at the same time creating a hypertension care model that can be emulated across the world

Heart and Stroke Foundation of Ontario (HSFO) high blood pressure strategy's hypertension management initiative study protocol

<p>Abstract</p> <p>Background</p> <p>Achieving control of hypertension prevents target organ damage at both the micro and macrovascular level and is a highly cost effective means of lowering the risk for heart attack and stroke particularly in people with diabetes. Clinical trials demonstrate that blood pressure control can be achieved in a large proportion of people. Translating this knowledge into widespread practice is the focus of the Hypertension Management Initiative, which began in 2004 with the goal of improving the management of this chronic health condition by primary care providers and patients in the community.</p> <p>Methods</p> <p>This study will test the effect of a systems change on the management of high blood pressure in real world practice in primary care in Ontario, Canada. The systems change intervention involves an interprofessional educational program bringing together physicians, nurses and pharmacists with tools for both providers and patients to facilitate blood pressure management. Each of two waves of subjects were enrolled over a 6 month period with the initial enrollment between waves separated by 9 months. Blood pressure will be measured with the BpTru ^®automated blood pressure device. To determine the effectiveness of the intervention, a before and after analysis within all subjects will compare blood pressure at baseline to annual measurements for the three year study. To assess whether the intervention has an impact on blood pressure control independent of community trends, a betwen group comparison of baseline blood pressures in the delayed wave will be made with the immediate wave during the same time period, so that the immediate wave has experienced the intervention for at least 9 months. The total enrollment goal is 5,000 subjects. The practice locations include 10 Family Health Teams (FHTs) and 1 Community Health Centre (CHC) and approximately 49 primary care physicians, 15 nurse practitioners, 37 registered nurses and over 150 community pharmacists across the 11 communities throughout the province of Ontario. The 11 primary care sites will be divided into immediate and delayed groups based on geography and the use of an electronic versus a traditional chart patient record.</p> <p>Discussion</p> <p>Initial consideration was given to randomizing the groups, however, for a number of reasons, this was deemed to not be possible. In order to ensure that the sites in the immediate intervention and delayed intervention groups are not different from each other, the sites will be assigned to the intervention groups manually to ensure a distribution of the variables as evenly as possible.</p> <p>Given that HSFO approached this particular group of health care providers to participate in a program relating to hypertension, this may have heightened their awareness of the issue and affected their management of patients with hypertension. Thus, data will be collected to allow an assessment of previous practice patterns and determine any impact of the Hawthorne Effect.</p> <p>Trial registration</p> <p>Clinicaltrials.gov NCT00425828</p

Individual atrasentan exposure is associated with long-term kidney and heart failure outcomes in patients with type 2 diabetes and chronic kidney disease

Atrasentan, an endothelin receptor antagonist, showed clinically significant albuminuria reduction with minimal signs of fluid retention in phase 2 trials. We evaluated whether plasma exposure was associated with long-term outcomes for kidney protection and heart failure in the phase 3 SONAR trial (n=3668) in type 2 diabetics with chronic kidney disease. A population pharmacokinetic model was used to estimate plasma exposure of atrasentan 0.75 mg/day. Parametric time-to-event models were used to quantify the association between plasma exposure and long-term outcomes. Mean atrasentan plasma exposure was 41.4 ng.h/mL (2.5th to 97.5th P: 14.2 to 139.9). Compared to placebo, a mean atrasentan exposure translated in a hazard ratio of 0.76 (95% CI: 0.28-0.85) for kidney events and 1.13 (95% CI: 1.03-2.20) for heart failure events. At the mean atrasentan exposure the kidney protective effect was larger than the increase in heart failure supporting the atrasentan 0.75 mg/day dose in this population

Renal Athersosclerotic reVascularization Evaluation (RAVE Study): Study protocol of a randomized trial [NCT00127738]

BACKGROUND: It is uncertain whether patients with renal vascular disease will have renal or mortality benefit from re-establishing renal blood flow with renal revascularization procedures. The RAVE study will compare renal revascularization to medical management for people with atherosclerotic renal vascular disease (ARVD) and the indication for revascularization. Patients will be assessed for the standard nephrology research outcomes of progression to doubling of creatinine, need for dialysis, and death, as well as other cardiovascular outcomes. We will also establish whether the use of a new inexpensive, simple and available ultrasound test, the renal resistance index (RRI), can identify patients with renal vascular disease who will not benefit from renal revascularization procedures[1]. METHODS/DESIGN: This single center randomized, parallel group, pilot study comparing renal revascularization with medical therapy alone will help establish an infrastructure and test the feasibility of answering this important question in clinical nephrology. The main outcome will be a composite of death, dialysis and doubling of creatinine. Knowledge from this study will be used to better understand the natural history of patients diagnosed with renal vascular disease in anticipation of a Canadian multicenter trial. Data collected from this study will also inform the Canadian Hypertension Education Program (CHEP) Clinical Practice Guidelines for the management of Renal and Renal Vascular Disease. The expectation is that this program for ARVD, will enable community based programs to implement a comprehensive guidelines based diagnostic and treatment program, help create an evidence based approach for the management of patients with this condition, and possibly reduce or halt the progression of kidney disease in these patients. DISCUSSION: Results from this study will determine the feasibility of a multicentered study for the management of renovascular disease

Rationale and protocol of the Study Of diabetic Nephropathy with AtRasentan (SONAR) trial:A clinical trial design novel to diabetic nephropathy

Aims Individuals with diabetes and chronic kidney disease (CKD) are at high risk for renal events. Recent trials of novel treatments have been negative, possibly because of variability in response to treatment of the target risk factor. Atrasentan is a selective endothelin A receptor antagonist that reduces urinary albumin‐to‐creatinine ratio (UACR), with a large variability between patients. We are assessing its effect on renal outcomes in the Study Of diabetic Nephropathy with AtRasentan (SONAR; NCT01858532) with an enrichment design (>30% lowering of albuminuria) to select patients most likely to benefit. Materials and Methods SONAR is a randomized, double‐blind, placebo‐controlled trial with approximately 3500 participants who have stage 2–4 CKD and macroalbuminuria and are receiving a maximum tolerated dose of a renin‐angiotensin system inhibitor. Results After 6 weeks of exposure to atrasentan 0.75 mg once daily (enrichment period), participants with ≥30% UACR decrease and no tolerability issues (responders) were randomly assigned to placebo or atrasentan 0.75 mg/day. The responder group will be used for primary efficacy and safety analyses. Approximately 1000 participants with <30% UACR reduction (non‐responders) were also randomized to placebo or atrasentan. The primary endpoint is a composite of a sustained doubling of serum creatinine or end‐stage renal disease. The original power calculation indicated that a total of 425 primary renal events in the responder group provides 90% power to detect a 27% reduction in relative risk (alpha level of .05). Conclusion SONAR aims to determine whether atrasentan added to guideline‐recommended therapies safely reduces the risk of CKD progression and delays the onset of end‐stage renal disease in patients with type 2 diabetes and nephropathy. SONAR also aims to establish whether the enrichment of patients based on their initial “surrogate” response to atrasentan will deliver a trial design in accord with personalized treatment of diabetic kidney disease

Blood pressure in chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

In September 2017, KDIGO (Kidney Disease: Improving Global Outcomes) convened a Controversies Conference titled Blood Pressure in Chronic Kidney Disease (CKD). The purpose of the meeting was to consider which recommendations from the 2012 KDIGO Clinical Practice Guideline for the Management of Blood Pressure in CKD should be reevaluated based on new evidence from clinical trials. Participants included a multidisciplinary panel of clinical and scientific experts. Discussions focused on the optimal means for measuring blood pressure (BP) as well as managing BP in CKD patients. Consistent with the 2012 Guideline, the conference did not address BP management in patients on maintenance dialysis

DreamTel; Diabetes risk evaluation and management tele-monitoring study protocol

<p>Abstract</p> <p>Background</p> <p>The rising prevalence of type 2 diabetes underlines the importance of secondary strategies for the prevention of target organ damage. While access to diabetes education centers and diabetes intensification management has been shown to improve blood glucose control, these services are not available to all that require them, particularly in rural and northern areas. The provision of these services through the Home Care team is an advance that can overcome these barriers. Transfer of blood glucose data electronically from the home to the health care provider may improve diabetes management.</p> <p>Methods and design</p> <p>The study population will consist of patients with type 2 diabetes with uncontrolled A1c levels living on reserve in the Battlefords region of Saskatchewan, Canada. This pilot study will take place over three phases. In the first phase over three months the impact of the introduction of the Bluetooth enabled glucose monitor will be assessed. In the second phase over three months, the development of guidelines based treatment algorithms for diabetes intensification will be completed. In the third phase lasting 18 months, study subjects will have diabetes intensification according to the algorithms developed.</p> <p>Discussion</p> <p>The first phase will determine if the use of the Bluetooth enabled blood glucose devices which can transmit results electronically will lead to changes in A1c levels. It will also determine the feasibility of recruiting subjects to use this technology. The rest of the Diabetes Risk Evaluation and Management Tele-monitoring (DreamTel) study will determine if the delivery of a diabetes intensification management program by the Home Care team supported by the Bluetooth enabled glucose meters leads to improvements in diabetes management.</p> <p>Trial Registration</p> <p>Protocol NCT00325624</p