Dataset Information

Topiroxostat versus allopurinol in patients with chronic heart failure complicated by hyperuricemia: A prospective, randomized, open-label, blinded-end-point clinical trial.

ABSTRACT:

Background

The benefits of xanthine oxidase inhibitors to chronic heart failure (CHF) patients is controversial. We investigated the beneficial effects of a novel xanthine oxidoreductase inhibitor, topiroxostat, in patients with CHF and hyperuricemia (HU), in comparison to allopurinol.

Methods and results

The prospective, randomized open-label, blinded-end-point study was performed in 141 patients with CHF and HU at 4 centers. Patients were randomly assigned to either topiroxostat or allopurinol group to achieve target uric acid level ≤6.0 mg/dL. According to the protocol, 140 patients were followed up for 24 weeks. Percent change in ln (N-terminal-proB-type natriuretic peptide) at week 24 (primary endpoint) was comparable between topiroxostat and allopurinol groups (1.6±8.2 versus -0.4±8.0%; P = 0.17). In the limited number of patients with heart failure with reduced ejection fraction (HFrEF) (left ventricle ejection fraction <45%), ratio of peak early diastolic flow velocity at mitral valve leaflet to early diastolic mitral annular motion velocity (E/e') decreased in topiroxostat group, but not in allopurinol group. Urinary 8-hydroxy-2'-deoxyguanosine and L-type fatty acid-binding protein levels increased and osmolality decreased significantly in allopurinol group, while these changes were less or absent in topiroxostat group. In allopurinol group HFrEF patients, additional to the increases in these urinary marker levels, urinary creatinine levels decreased, with no change in clearance, but not in topiroxostat group.

Conclusions

Compared with allopurinol, topiroxostat did not show great benefits in patients with CHF and HU. However, topiroxostat might have potential advantages of reducing left ventricular end-diastolic pressure, not worsening oxidative stress in proximal renal tubule, and renoprotection over allopurinol in HFrEF patients.

SUBMITTER: Sakuma M

PROVIDER: S-EPMC8789120 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:IntroductionPeople suffering from leg muscle weakness caused by neuromuscular disorders (NMDs) are often provided with leg orthoses to reduce walking problems such as increased walking effort, diminished walking speed, reduced balance and falls. However, evidence for the effectiveness of leg orthoses to improve walking in this patient group is limited and there is an absence of standardised practice in orthotic prescription. In 2012 a Dutch multidisciplinary guideline was developed aimed to standardise the orthotic treatment process in NMD. Although application of the guideline in expert centres (specialised orthotic care) seems beneficial regarding clinical effectiveness, larger studies are necessary to confirm results and investigate cost-effectiveness. Therefore, this study aims to examine the effectiveness and cost-effectiveness of specialised orthotic care compared with usual orthotic care in adults with slowly progressive NMD.Methods and analysisA prospective randomised open-label blinded end-point study will be performed, in which 70 adults with slowly progressive NMD are randomly assigned to specialised orthotic care (intervention) or usual orthotic care (control). Outcome measures are assessed at baseline and at 3 and 6 months follow-up. The primary endpoints are gross walking energy cost (J/kg/m) assessed during a 6 min walk test and achievement of personal goals, measured with the Goal Attainment Scale. Secondary endpoints include walking speed, gait biomechanics, stability, physical functioning, falls and fear of falling, perceived fatigue and satisfaction. For the economic evaluation, societal costs and health-related quality of life will be assessed using cost questionnaires and the 5-Level version of EuroQol 5 Dimension, retrospectively.Ethics and disseminationThe study is registered in the Dutch trial register (NL 7511) and the protocol has been approved by the Medical Ethics Committee of the Academic Medical Center in Amsterdam. Results will be presented at national and international scientific conferences and disseminated through peer-reviewed journals and media aimed at a broad audience including patients.

Project description:IntroductionSleep-time blood pressure correlates more strongly with adverse cardiovascular events than does daytime blood pressure. The BedMed trial evaluates whether bedtime antihypertensive administration, as compared with conventional morning use, reduces major adverse cardiovascular events. METHODS AND ANALYSIS: DesignProspective randomised, open-label, blinded end-point trial.ParticipantsHypertensive primary care patients using blood pressure lowering medication and free from glaucoma.SettingCommunity primary care providers in 5 Canadian provinces (British Columbia, Alberta, Saskatchewan, Manitoba and Ontario) are mailing invitations to their eligible patients. Social media campaigns (Google, Facebook) are additionally running in the same provinces.InterventionConsenting participants are allocated via central randomisation to bedtime vs morning use of all antihypertensives.Follow-up(1) Telephone or email questionnaire at 1 week, 6 weeks, 6 months and every 6 months thereafter, and (2) accessing linked governmental healthcare databases tracking hospital and community medical services.Primary outcomeComposite of all-cause death, or hospitalisation for myocardial infarction/acute-coronary syndrome, stroke or congestive heart failure.Secondary outcomesEach primary outcome element on its own, all-cause hospitalisation or emergency department visit, long-term care admission, non-vertebral fracture, new glaucoma diagnosis, 18-month cognitive decline from baseline (via Short Blessed Test).Select other outcomesSelf-reported nocturia burden at 6 weeks and 6 months (no, minor or major burden), 1-year self-reported overall health score (EQ-5D-5L), self-reported falls, total cost of care (acute and community over study duration) and mean sleep-time systolic blood pressure after 6 months (via 24-hour monitor in a subset of 302 sequential participants).Primary outcome analysisCox proportional hazards survival analysis.Sample sizeThe trial will continue until a projected 254 primary outcome events have occurred.Current statusEnrolment ongoing (3227 randomised to date).Ethics and disseminationBedMed has ethics approval from six research ethics review boards and will publish results in a peer-reviewed journal.Trial registration numberNCT02990663.

Project description:IntroductionDual antiplatelet therapy and high-intensity statins are the mainstay treatment in patients with acute stage, symptomatic intracranial atherosclerotic stenosis (ICAS). Alirocumab is a monoclonal antibody that can inhibit proprotein convertase subtilisin-kexin type 9 and effectively lower low-density lipoprotein cholesterol levels with less side effects than statins. We hypothesise that alirocumab treatment in addition to statin therapy could stabilise intracranial plaque and reduce arterial stenosis.Methods and analysisIn this prospective, randomised, open-label, blinded end-point study, we will use high-resolution vessel-wall MRI to evaluate the efficacy and safety of alirocumab in patients who had an acute ischaemic stroke from ICAS. We will recruit 66 patients who had an acute ischaemic stroke within 7 days of symptom onset, who had symptomatic intracranial artery stenosis (>30%) at the middle cerebral artery, basilar artery or intracranial internal carotid artery. Among them, 22 patients will be randomised to the intervention group to receive treatment with 75 mg alirocumab subcutaneously every 2 weeks for a total of 26 weeks, while those in the control group will not. All patients in both groups will receive antiplatelet agents and high-intensity statins, including 20 mg rosuvastatin or 40-80 mg atorvastatin or at the maximum tolerated dose. All of them will undergo MRI at recruitment and after 26 weeks. The primary outcomes are changes in intracranial atherosclerotic plaques in the MRI before and after 6 months treatment. This trial is being conducted at Chang Gung Memorial Hospital at Chiayi, Taiwan.Ethics and disseminationThis trial has been approved by the Institutional Review Board of Chang Gung Memorial Hospital (approval no. 202 002 482A3). Written informed consent will be obtained from all research participants. Study results will be published as peer-reviewed articles.Trial registration numberClinicalTrials.gov, Identifier: NCT05001984; Pre-results.

Project description:BackgroundMinorities have an increased incidence of early-onset, obesity-related cerebrovascular disease. Unfortunately, effective weight management in this vulnerable population has significant barriers.ObjectiveOur objective was to determine the feasibility and preliminary treatment effects of a smartphone-based weight loss intervention versus food journals to monitor dietary patterns in minority stroke patients.MethodsSwipe out Stroke was a pilot prospective randomized controlled trial with open blinded end point. Minority stroke patients and their caregivers were screened for participation using cluster enrollment. We used adaptive randomization for assignment to a behavior intervention with (1) smartphone-based self-monitoring or (2) food journal self-monitoring. The smartphone group used Lose it! to record meals and communicate with us. Reminder messages (first 30 days), weekly summaries plus reminder messages on missed days (days 31-90), and weekly summaries only (days 91-180) were sent via push notifications. The food journal group used paper diaries. Both groups received 4 in-person visits (baseline and 30, 90, and 180 days), culturally competent counseling, and educational materials. The primary outcome was reduced total body weight.ResultsWe enrolled 36 stroke patients (n=23, 64% African American; n=13, 36% Hispanic), 17 in the smartphone group, and 19 in the food journal group. Mean age was 54 (SD 9) years; mean body mass index was 35.7 (SD 5.7) kg/m2; education, employment status, and family history of stroke or obesity did not differ between the groups. Baseline rates of depression (Patient Health Questionnaire-9 [PHQ-9] score median 5.5, IQR 3.0-9.5), cognitive impairment (Montreal Cognitive Assessment score median 23.5, IQR 21-26), and inability to ambulate (5/36, 14% with modified Rankin Scale score 3) were similar. In total, 25 (69%) stroke survivors completed Swipe out Stroke (13/17 in the smartphone group, 12/19 in the food journal group); 1 participant in the smartphone group died. Median weight change at 180 days was 5.7 lb (IQR -2.4 to 8.0) in the smartphone group versus 6.4 lb (IQR -2.2 to 12.5; P=.77) in the food journal group. Depression was significantly lower at 30 days in the smartphone group than in the food journal group (PHQ-9 score 2 vs 8; P=.03). Clinically relevant depression rates remained in the zero to minimal range for the smartphone group compared with mild to moderate range in the food journal group at day 90 (PHQ-9 score 3.5 vs 4.5; P=.39) and day 180 (PHQ-9 score 3 vs 6; P=.12).ConclusionsIn a population of obese minority stroke survivors, the use of a smartphone did not lead to a significant difference in weight change compared with keeping a food journal. The presence of baseline depression (19/36, 53%) was a confounding variable, which improved with app engagement. Future studies that include treatment of poststroke depression may positively influence intervention efficacy.Trial registrationClinicalTrials.gov NCT02531074; https://www.clinicaltrials.gov/ct2/show/NCT02531074.