Dataset Information

Rivaroxaban for stroke patients with antiphospholipid syndrome (RISAPS): protocol for a randomized controlled, phase IIb proof-of-principle trial.

ABSTRACT:

Background

Optimal secondary prevention antithrombotic therapy for patients with antiphospholipid syndrome (APS)-associated ischemic stroke, transient ischemic attack, or other ischemic brain injury is undefined. The standard of care, warfarin or other vitamin K antagonists at standard or high intensity (international normalized ratio (INR) target range 2.0-3.0/3.0-4.0, respectively), has well-recognized limitations. Direct oral anticoagulants have several advantages over warfarin, and the potential role of high-dose direct oral anticoagulants vs high-intensity warfarin in this setting merits investigation.

Objectives

The Rivaroxaban for Stroke patients with APS trial (RISAPS) seeks to determine whether high-dose rivaroxaban could represent a safe and effective alternative to high-intensity warfarin in adult patients with APS and previous ischemic stroke, transient ischemic attack, or other ischemic brain manifestations.

Methods

This phase IIb prospective, randomized, controlled, noninferiority, open-label, proof-of-principle trial compares rivaroxaban 15 mg twice daily vs warfarin, target INR range 3.0-4.0. The sample size target is 40 participants. Triple antiphospholipid antibody-positive patients are excluded. The primary efficacy outcome is the rate of change in brain white matter hyperintensity volume on magnetic resonance imaging, a surrogate marker of presumed ischemic damage, between baseline and 24 months follow-up. Secondary outcomes include additional neuroradiological and clinical measures of efficacy and safety. Exploratory outcomes include high-dose rivaroxaban pharmacokinetic modeling.

Conclusion

Should RISAPS demonstrate noninferior efficacy and safety of high-dose rivaroxaban in this APS subgroup, it could justify larger prospective randomized controlled trials.

SUBMITTER: Mittal P

PROVIDER: S-EPMC11321294 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature

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Publications

Rivaroxaban for stroke patients with antiphospholipid syndrome (RISAPS): protocol for a randomized controlled, phase IIb proof-of-principle trial.

Mittal Prabal P Gafoor Rafael R Sayar Zara Z Efthymiou Maria M Tohidi-Esfahani Ibrahim I Appiah-Cubi Stella S Arachchillage Deepa J DJ Atkinson David D Bordea Ekaterina E Cardoso M Jorge MJ Caverly Emilia E Chandratheva Arvind A Chau Marisa M Freemantle Nick N Gates Carolyn C Ja Ger H Rolf HR Kaul Arvind A Mitchell Chris C Nguyen Hanh H Packham Bunis B Paskell Jaye J Patel Jignesh P JP Round Chris C Sanna Giovanni G Zaidi Abbas A Werring David J DJ Isenberg David D Cohen Hannah H

Research and practice in thrombosis and haemostasis 20240605 5

<h4>Background</h4>Optimal secondary prevention antithrombotic therapy for patients with antiphospholipid syndrome (APS)-associated ischemic stroke, transient ischemic attack, or other ischemic brain injury is undefined. The standard of care, warfarin or other vitamin K antagonists at standard or high intensity (international normalized ratio (INR) target range 2.0-3.0/3.0-4.0, respectively), has well-recognized limitations. Direct oral anticoagulants have several advantages over warfarin, and t ...[more]

PMID: 39139554

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Project description:IntroductionDehydroepiandrosterone (DHEA) has been proposed to improve pregnancy rates in women with diminished ovarian reserve undergoing in vitro fertilisation (IVF) treatment. However, evidence regarding its efficacy is supported by a limited number of randomised controlled trials (RCTs). This double-blinded RCT aims to measure the effect of DHEA supplementation prior to and during controlled ovarian hyperstimulation on ovarian response prior to IVF treatment in women predicted to have poor ovarian reserve.Methods and analysisSixty women with ovarian antral follicle count ≤10 and serum anti-Mullerian hormone ≤5 pmol/L undergoing IVF/intracytoplasmic sperm injection (ICSI) treatment at the Nurture fertility clinic, Nottingham will be recruited. They will be randomised to either receive DHEA capsule 75 mg/day or placebo for at least 12 weeks before egg collection. All participants will undergo standard long down regulation protocol using human menopausal gonadotropin 300 IU/day. Serum samples and follicular fluids at the time of egg collection will be collected for hormonal immunoassays. For ICSI participants, cumulus cells stripped from oocyte will be collected for cumulus gene expression analyses regarding oocyte competence. Microdrops of oocyte culture media before the time of ICSI will be assessed for glucose, pyruvate and lactate utilisation. Embryo transfer will be performed on day 2, 3 or 5 based on the number and quality of the embryos available. Pregnancy will be defined as urine pregnancy test positive (biochemical pregnancy) and 6-8 weeks ultrasound scan with fetal heart beat (clinical pregnancy) and live birth. It is planned to perform the molecular and nutritional fingerprint analyses in batches after finishing the clinical phase of the study.Ethics and disseminationThe approval of the study was granted by the NHS Research Ethics Committee (Ref number NRES 12/EM/0002), the Medicines and Healthcare products Regulatory Agency (MHRA), and the Nottingham University Hospitals Trust Research and Development department. All participants shall provide written informed consent before being randomised into allocated treatment groups.Trial registration numberProtocol V.2.0; EudraCT number: 2011-002425-21; http://www.clinicaltrials.gov; NCT01572025; CTA reference: 03057/0053/001-0002.

Project description:BackgroundLabile blood pressure after acute ischaemic stroke requiring mechanical thrombectomy is independently associated with poor patient outcomes.ObjectivesThis study protocol describes is designed to determine whether transauricular nerve stimulation, improves baroreflex sensitivity, reduces blood pressure variability in the first 24 hours after acute ischaemic stroke requiring mechanical thrombectomy.Design: phase 2a, proof-of-concept, sham-controlled randomised trialMethods and Analysis: 36 individuals undergoing mechanical thrombectomy for acute ischaemic stroke with established hypertension aged >18 years will be randomly allocated to receive bilateral active or sham transauricular nerve stimulation for the duration of the mechanical thrombectomy procedure (AffeX-CT/001 investigational device). The intervention will be repeated for 1h the morning following the mechanical thrombectomy. Non-invasive blood pressure will be measured ≥2h for 24h after mechanical thrombectomy. Holter electrocardiographic monitoring will be recorded during transauricular nerve stimulation. Participants, clinicians and investigators will be masked to treatment allocations. The primary outcome will be the coefficient of variation of systolic blood pressure. Secondary outcomes include additional estimates of blood pressure variability and time/frequency-domain measures of autonomic cardiac modulation An adjusted sample size of 36 patients is required to have a 90% chance of detecting, as significant at the 5% level, a difference in the coefficient of variation in systolic blood pressure of 5±4mmHg between sham and active stimulation [assuming 5% non-compliance rate in each group]. Ethics: confirmed on 16 March 2023 by HRA and Health and Care Research Wales ethics committee (reference 23/WA/0013).DiscussionThis study will provide proof-of-concept data that examines whether non-invasive autonomic neuromodulation can be used to favourably modify blood pressure and autonomic control after acute ischaemic stroke requiring mechanical thrombectomy.Trial registrationTrial registration number: NCT05417009.

Dataset Information

Rivaroxaban for stroke patients with antiphospholipid syndrome (RISAPS): protocol for a randomized controlled, phase IIb proof-of-principle trial.

Background

Objectives

Methods

Conclusion

Publications

Rivaroxaban for stroke patients with antiphospholipid syndrome (RISAPS): protocol for a randomized controlled, phase IIb proof-of-principle trial.

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