Rationale and design of CONTINUITY: a Phase 4 randomized controlled trial of continued post-discharge sodium zirconium cyclosilicate treatment versus standard of care for hyperkalemia in chronic kidney disease.

Background: Individuals with chronic kidney disease (CKD) hospitalized with hyperkalemia are at risk of hyperkalemia recurrence and re-hospitalization. We present the rationale and design of CONTINUITY, a study to examine the efficacy of continuing sodium zirconium cyclosilicate (SZC)-an oral, highly selective potassium (K+) binder-compared with standard of care (SoC) on maintaining normokalemia and reducing re-hospitalization and resource utilization among participants with CKD hospitalized with hyperkalemia. Methods: This Phase 4, randomized, open-label, multicenter study will enroll adults with Stage 3b-5 CKD and/or estimated glomerular filtration rate <45 mL/min/1.73 m2, within 3 months of eligibility screening, hospitalized with a serum potassium (sK+) level of >5.0-≤6.5 mmol/L, without ongoing K+ binder treatment. The study will include an in-hospital phase, where participants receive SZC for 2-21 days, and an outpatient (post-discharge) phase. At discharge, participants with sK+ 3.5-5.0 mmol/L will be randomized (1:1) to SZC or SoC and monitored for 180 days. The primary endpoint is the occurrence of normokalemia at 180 days. Secondary outcomes include incidence and number of hospital admissions or emergency department visits both with hyperkalemia as a contributing factor, and renin-angiotensin-aldosterone system inhibitor down-titration. The safety and tolerability of SZC will be evaluated.Ethics approval has been received from all relevant ethics committees. Enrollment started March 2022 and the estimated study end date is December 2023. Conclusions: This study will assess the potential of SZC versus SoC in managing people with CKD and hyperkalemia post-discharge. Trial registration: ClinicalTrials.gov identifier: NCT05347693; EudraCT: 2021-003527-14, registered on 19 October 2021.

Use of a Digital Chronic Obstructive Pulmonary Disease Respiratory Tracker in a Primary Care Setting: A Feasibility Study.

INTRODUCTION: Telemonitoring is a promising self-management strategy to improve health care outcomes. This study evaluated real-world adoption of the chronic obstructive pulmonary disease (COPD) Co-Pilot daily symptom monitoring tool by patients and primary care providers (PCPs). METHODS: An open-label, 6-month, single-arm, multicenter, noninterventional feasibility study enrolled 97 patients aged ≥ 40 years with symptomatic or poorly controlled COPD and ≥ 10 pack-year smoking history. Patients received smartphones and training to use the COPD Co-Pilot application. During the study, patients tracked symptoms daily; an increase in symptom score of ≥ 1.0 point from baseline (symptom alert) prompted patients to contact their PCP via toll-free number. The primary endpoint was time to clinical recommendation (TTCR) from a symptom alert; adherence to completing daily symptom reports through the COPD Co-Pilot application and patient satisfaction were also measured. RESULTS: Overall, 87 of 96 patients (90.6%) received 2142 symptom alerts; 42 alerts (equivalent to 2% of all symptom alerts) resulted in 23 patients contacting their PCP. Median TTCR was 7.1 h (interquartile range [IQR]: 4.0-29.9). Among 15 patients using the toll-free number, median TTCR was 2.1 h (IQR 0.0-7.2) versus 19.6 h (IQR 4.5-45.2) for eight patients using other contact methods. Average COPD Co-Pilot adherence overall was 75.2% (95% CI 74.6-75.9). Patients responded favorably regarding the application's ease of use, functionality, and information provided. CONCLUSIONS: The COPD Co-Pilot tool was associated with relatively high levels of adherence, suggesting patients' willingness to monitor symptoms daily. Although a limited number of patients initiated PCP contact, patients who used the study-provided toll-free number had substantially shorter median TTCR, suggesting that this tool could help empower patients to better manage their COPD.

Copayment Reduction Voucher Utilization and Associations With Medication Persistence and Clinical Outcomes: Findings From the ARTEMIS Trial.

BACKGROUND: Cost is frequently cited as a barrier to optimal medication use, but the extent to which copayment assistance interventions are used when available, and their impact on evidence-based medication persistence and major adverse cardiovascular events is unknown. METHODS AND RESULTS: The ARTEMIS trial (Affordability and Real-World Antiplatelet Treatment Effectiveness After Myocardial Infarction Study) randomized 301 hospitals to usual care versus the ability to provide patients with vouchers that offset copayment costs when filling P2Y12 inhibitors in the 1 year post-myocardial infarction. In the intervention group, we used multivariable logistic regression to identify patient and medication cost characteristics associated with voucher use. We then used this model to stratify both intervention and usual care patients by likelihood of voucher use, and examined the impact of the voucher intervention on 1-year P2Y12 inhibitor persistence (no gap in pharmacy supply >30 days) and major adverse cardiovascular events (all-cause death, myocardial infarction, or stroke). Among 10 102 enrolled patients, 6135 patients were treated at hospitals randomized to the copayment intervention. Of these, 1742 (28.4%) never used the voucher, although 1729 (99.2%) voucher never-users filled at least one P2Y12 inhibitor prescription in the 1 year post-myocardial infarction. Characteristics most associated with voucher use included: discharge on ticagrelor, planned 1-year course of P2Y12 inhibitor treatment, white race, commercial insurance, and higher out-of-pocket medication costs (c-statistic 0.74). Applying this propensity model to stratify all enrolled patients by likelihood of voucher use, the intervention improved medication persistence the most in patients with high likelihood of voucher use (adjusted interaction P=0.03, odds ratio, 1.86 [95% CI, 1.48-2.33]). The intervention did not significantly reduce major adverse cardiovascular events in any voucher use likelihood group, although the odds ratio was lowest (0.86 [95% CI, 0.56-1.16]) among patients with high likelihood of voucher use (adjusted interaction P=0.04). CONCLUSIONS: Among patients discharged after myocardial infarction, those with higher copayments and greater out-of-pocket medication costs were more likely to use a copayment assistance voucher, but some classes of patients were less likely to use a copayment assistance voucher. Patients at low likelihood of voucher use benefitted least from copayment assistance, and other interventions may be needed to improve medication-taking behaviors and clinical outcomes in these patients. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02406677.

Impact of a Copayment Reduction Intervention on Medication Persistence and Cardiovascular Events in Hospitals With and Without Prior Medication Financial Assistance Programs.

Background Hospitals commonly provide a short-term supply of free P2Y12 inhibitors at discharge after myocardial infarction, but it is unclear if these programs improve medication persistence and outcomes. The ARTEMIS (Affordability and Real-World Antiplatelet Treatment Effectiveness After Myocardial Infarction Study) trial randomized hospitals to usual care versus waived P2Y12 inhibitor copayment costs for 1-year post-myocardial infarction. Whether the impact of this intervention differed between hospitals with and without pre-existing medication assistance programs is unknown. Methods and Results In this post hoc analysis of the ARTEMIS trial, we examined the associations of pre-study free medication programs and the randomized copayment voucher intervention with P2Y12 inhibitor persistence (measured by pharmacy fills and patient report) and major adverse cardiovascular events using logistic regression models including a propensity score. Among 262 hospitals, 129 (49%) offered pre-study free medication assistance. One-year P2Y12 inhibitor persistence and major adverse cardiovascular events risks were similar between patients treated at hospitals with and without free medication programs (adjusted odds ratio 0.93, 95% CI, 0.82-1.05 and hazard ratio 0.92, 95% CI, 0.80-1.07, respectively). The randomized copayment voucher intervention improved persistence, assessed by pharmacy fills, in both hospitals with (53.6% versus 44.0%, adjusted odds ratio 1.45, 95% CI, 1.20-1.75) and without (59.0% versus 48.3%, adjusted odds ratio 1.46, 95% CI, 1.25-1.70) free medication programs (Pinteraction=0.71). Differences in patient-reported persistence were not significant after adjustment. Conclusions While hospitals commonly report the ability to provide free short-term P2Y12 inhibitors, we did not find association of this with medication persistence or major adverse cardiovascular events among patients with insurance coverage for prescription medication enrolled in the ARTEMIS trial. An intervention that provided copayment assistance vouchers for 1 year was successful in improving medication persistence in hospitals with and without pre-existing short-term medication programs. Registration URL: https://www.clini​caltr​ials.gov/. Unique identifier: NCT02406677.