Angiotensin receptor blockers for the treatment of covid-19: pragmatic, adaptive, multicentre, phase 3, randomised controlled trial.

OBJECTIVE: To determine whether disrupting the renin angiotensin system with angiotensin receptor blockers will improve clinical outcomes in people with covid-19. DESIGN: CLARITY was a pragmatic, adaptive, multicentre, phase 3, randomised controlled trial. SETTING: 17 hospital sites in India and Australia. PARTICIPANTS: Participants were at least 18 years old, previously untreated with angiotensin receptor blockers, with a laboratory confirmed diagnosis of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection who had been admitted to hospital for management of covid-19. INTERVENTION: Oral angiotensin receptor blockers (telmisartan in India) or placebo (1:1) for 28 days. MAIN OUTCOME MEASURES: The primary endpoint was covid-19 disease severity using a modified World Health Organization Clinical Progression Scale (WHO scale) at day 14. Secondary outcomes were WHO scale scores at day 28, mortality, intensive care unit admission, and respiratory failure. Analyses were evaluated on an ordinal scale in the intention-to-treat population. RESULTS: Between 3 May 2020 and 13 November 2021, 2930 people were screened for eligibility, with 393 randomly assigned to angiotensin receptor blockers (of which 388 (98.7%) to telmisartan 40 mg/day) and 394 to the control group. 787 participants were randomised: 778 (98.9%) from India and nine (1.1%) from Australia. The median WHO scale score at day 14 was 1 (interquartile range 1-1) in 384 participants assigned angiotensin receptor blockers and 1 (1-1) in 382 participants assigned placebo (adjusted odds ratio 1.51 (95% credible interval 1.02 to 2.23), probability of an odds ratio of >1 (Pr(OR>1)=0.98). WHO scale scores at day 28 showed little evidence of difference between groups (1.02 (0.55 to 1.87), Pr(OR>1)=0.53). The trial was stopped when a prespecified futility rule was met. CONCLUSIONS: In patients admitted to hospital for covid-19, mostly with mild disease, not requiring oxygen, no evidence of benefit, based on disease severity score, was found for treatment with angiotensin receptor blockers, using predominantly 40 mg/day of telmisartan. TRIAL REGISTRATION: ClinicalTrials.gov NCT04394117.

Impact of supplemental private health insurance on dialysis and outcomes.

BACKGROUND: The influence of health insurance systems on the treatment of end-stage kidney disease (ESKD) patients ispoorly understood. AIM: We investigated how supplemental private health insurance (PHI) coverage impacted ESKD treatment modalitiesand patient outcomes. The influence of health insurance systems on the treatment of end-stage kidney disease (ESKD) patients is poorly understood. We investigated how supplemental private health insurance (PHI) coverage impacted ESKD treatment modalities and patient outcomes. METHODS: All adult patients commencing ESKD treatment in New South Wales, Australia from 2000 to 2010 were identified using the Australia and New Zealand Dialysis and Transplant Registry. Data were linked to the state hospitalisation dataset to obtain insurance status, allowing the comparisons of mortality, ESKD treatment modality and health service utilisation between privately insured and public patients. RESULTS: The cohort of 5737 patients included 38% (n = 2152) with PHI. At 1 year after ESKD treatment initiation, PHI patients had lower mortality (hazard ratio 0.84, 95% confidence interval (CI) 0.74-0.95, P = 0.01), were more likely to be receiving home haemodialysis (HD) (odds ratio (OR) 1.38, 95% CI 1.01-1.89, P = 0.04), to have been transplanted (OR 1.75, 95% CI 1.25-2.46, P = 0.001) and used fewer hospital days (incidence rate ratio 0.85, 95% CI 0.74-0.96, P = 0.01). After adjustment, PHI patients were more likely to initiate ESKD treatment with facility-based HD (OR 1.22, 95% CI 1.01-1.46, P = 0.03) but were less likely to be started on peritoneal dialysis (OR 0.81, 95% CI 0.67-0.98, P = 0.03). CONCLUSION: Our findings suggest that supplemental PHI in Australia is associated with lower-risk ESKD treatment attributes and improved health outcomes. A greater understanding of the treatment pathways that deliver these outcomes may inform treatment for the broader ESKD treatment population.

Buttonhole cannulation and clinical outcomes in a home hemodialysis cohort and systematic review.

BACKGROUND AND OBJECTIVES: The relative merits of buttonhole (or blunt needle) versus rope ladder (or sharp needle) cannulation for hemodialysis vascular access are unclear. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Clinical outcomes by cannulation method were reviewed in 90 consecutive home hemodialysis patients. Initially, patients were trained in rope ladder cannulation. From 2004 on, all incident patients were started on buttonhole cannulation, and prevalent patients were converted to this cannulation method. Coprimary outcomes were arteriovenous fistula-attributable systemic infections and a composite of arteriovenous fistula loss or requirement for surgical intervention. Secondary outcomes were total arteriovenous fistula-related infections and staff time requirements. Additionally, a systematic review evaluating infections by cannulation method was performed. RESULTS: Seventeen systemic arteriovenous fistula-attributable infections were documented in 90 patients who were followed for 3765 arteriovenous fistula-months. Compared with rope ladder, buttonhole was not associated with a significantly higher rate of systemic arteriovenous fistula-attributable infections (incidence rate ratio, 2.71; 95% confidence interval, 0.66 to 11.09; P=0.17). However, use of buttonhole was associated with a significantly higher rate of total arteriovenous fistula infections (incidence rate ratio, 3.85; 95% confidence interval, 1.66 to 12.77; P=0.03). Initial and ongoing staff time requirements were significantly higher with buttonhole cannulation. Arteriovenous fistula loss or requirement for surgical intervention was not different between cannulation methods. A systematic review found increased arteriovenous fistula-related infections with buttonhole compared with rope ladder in four randomized trials (relative risk, 3.34; 95% confidence interval, 0.91 to 12.20), seven observational studies comparing before with after changes (relative risk, 3.15; 95% confidence interval, 1.90 to 5.21), and three observational studies comparing units with different cannulation methods (relative risk, 3.27; 95% confidence interval, 1.44 to 7.43). CONCLUSION: Buttonhole cannulation was associated with higher rates of infectious events, increased staff support requirements, and no reduction in surgical arteriovenous fistula interventions compared with rope ladder in home hemodialysis patients. A systematic review of the published literature found that buttonhole is associated with higher risk of arteriovenous fistula-related infections.

Comparative efficacy of a team-led treatment protocol for the management of renal anaemia.

AIM: To evaluate the efficacy of a team-led anaemia management protocol based on current guidelines. METHODS: The effect of a treatment protocol in implementing an anaemia guideline was evaluated in a large teaching hospital, encompassing three (two in-hospital and one satellite) dialysis facilities. Quarterly data were collected, over a 6-year period, on all patients dialysing in these facilities, before and after implementation of an anaemia management treatment protocol. This protocol was developed by a physician-led team and implemented by an anaemia coordinator assisted by the unit staff. The primary outcome measure was the proportion of patients receiving erythropoietin with ferritin levels within the national guidelines target range calculated using data on haemoglobin (Hb), iron studies, dry weight and erythropoietin dose. RESULTS: Data was collected on >150 patients every quarter between 2005 and 2010 (inclusive). The proportion of patients within the primary outcome target range increased from a nadir of 17% to 51% with evidence of true systematic change. The proportion of patients with Hb values within the unit target range also increased from 46% to 56% (P = 0.25) between the first and last years of the project. These changes were also associated with reduced erythropoietin drug use down to 0.44 µg/kg per week. CONCLUSION: Implementation of a treatment protocol for anaemia management in haemodialysis patients was associated with greater consistency with guideline evidence and lower drug use. Achieving such guideline recommendations for ferritin targets in more than 50% of patients appears feasible.