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Multicentre randomised placebo-controlled trial of oral anticoagulation with apixaban in systemic sclerosis-related pulmonary arterial hypertension: the SPHInX study protocol

Citation

Calderone, A and Stevens, W and Prior, D and Nandurkar, H and Gabbay, E and Proudman, SM and Williams, T and Celemajer, D and Sahhar, J and Wong, PKK and Thakkar, V and Dwyer, N and Wrobel, J and Chin, W and Liew, D and Staples, M and Buchbinder, R and Nikpour, M, Multicentre randomised placebo-controlled trial of oral anticoagulation with apixaban in systemic sclerosis-related pulmonary arterial hypertension: the SPHInX study protocol, BMJ Open, 6, (12) pp. 1-13. ISSN 2044-6055 (2016) [Refereed Article]


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Licensed under Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) https://creativecommons.org/licenses/by-nc/4.0/

DOI: doi:10.1136/bmjopen-2016-011028

Abstract

Introduction: Systemic sclerosis (SSc) is a severe and costly multiorgan autoimmune connective tissue disease characterised by vasculopathy and fibrosis. One of the major causes of SSc-related death is pulmonary arterial hypertension (PAH), which develops in 1215% of patients with SSc and accounts for 3040% of deaths. In situ thrombosis in the small calibre peripheral pulmonary vessels resulting from endothelial dysfunction and an imbalance of anticoagulant and prothrombotic mediators has been implicated in the complex pathophysiology of SSc-related PAH (SSc-PAH), with international clinical guidelines recommending the use of anticoagulants for some types of PAH, such as idiopathic PAH. However, anticoagulation has not become part of standard clinical care for patients with SSc-PAH as only observational evidence exists to support its use. Therefore, we present the rationale and methodology of a phase III randomised controlled trial (RCT) to evaluate the efficacy, safety and cost-effectiveness of anticoagulation in SSc-PAH.

Methods and analysis: This Australian multicentre RCT will compare 2.5 mg apixaban with placebo, in parallel treatment groups randomised in a 1:1 ratio, both administered twice daily for 3 years as adjunct therapy to stable oral PAH therapy. The composite primary outcome measure will be the time to death or clinical worsening of PAH. Secondary outcomes will include functional capacity, health-related quality of life measures and adverse events. A cost-effectiveness analysis of anticoagulation versus placebo will also be undertaken.

Ethics and dissemination: Ethical approval for this RCT has been granted by the Human Research Ethics Committees of all participating centres. An independent data safety monitoring board will review safety and tolerability data for the duration of the trial. The findings of this RCT are to be published in open access journals.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Cardiorespiratory Medicine and Haematology
Research Field:Cardiology (incl. Cardiovascular Diseases)
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Cardiovascular System and Diseases
Author:Dwyer, N (Dr Nathan Dwyer)
ID Code:118357
Year Published:2016
Deposited By:Medicine (Discipline)
Deposited On:2017-07-11
Last Modified:2017-11-08
Downloads:4 View Download Statistics

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