Intensive Urate Lowering Therapy of Febuxostat Compared to Allopurinol on Cardiovascular Risk in Patients With Gout — FORWARD  

Gout Clinical Trial

Official title: The Effect of Intensive Urate Lowering Therapy (ULT) With Febuxostat in Comparison With Allopurinol on Cardiovascular Risk in Patients With Gout Using Surrogate Markers: a Randomized, Controlled Trial

Status Completed

Clinical Trial Summary

There is a mounting and clear association between hyperuricaemia, gout and the presence of traditional cardiovascular (CV) risk factors and CV event-equivalent conditions such as chronic kidney disease, metabolic syndrome, and diabetes. Gout is associated with increased risk of CV events such as myocardial infarction and CV death. Furthermore hyperuricaemia is clearly associated with an increased arterial stiffness, a marker of pre-clinical atherosclerosis. Carotid-femoral pulse wave velocity (PWV) is the "gold standard" measurement of arterial stiffness and it is considered, in this trial, as a valid surrogate endpoint with clearly established relevance to predict cardiovascular disease (CVD) clinical outcome In this randomised trial conducted on adult subjects with a history of gout, we use surrogate endpoints to investigate the efficacy of febuxostat compared with allopurinol to predict (CVD) clinical outcome.

Eligible subjects were randomised in a 1:1 ratio to the following treatment groups:

• Test product: febuxostat 80 mg or 120 mg once daily (120 mg daily, if serum urate was >6 mg/dL after 2 weeks of treatment at 80 mg daily).

• Active comparator: allopurinol 100 mg once daily (up to a maximum dose of 600 mg daily escalated in 100 mg increments every 2 weeks, if serum urate acid (sUA) was >6 mg/dL after 2 weeks of treatment at the previous dose).

The study duration was 39 weeks, which included the:

• Run-in/screening period: 1 week (extendable up to a maximum of 30 days according to variability of sUA levels);

• Treatment period: 36 weeks;

• Safety follow-up period: 2 weeks.

Clinical Trial Description

The study physician, responsible for randomization and drug supply handling, is unblinded to study medications and therefore will not be involved in the main efficacy evaluations of each patient randomized in the study.

Conversely, the study physician/s responsible for the main efficacy evaluation (Pulse Wave Velocity) will be blind to study treatments.

Key efficacy variables will be performed by an independent centralized laboratory.

Trial was conducted in a detailed and orderly manner in accordance with established research principles, International Conference on Harmonization (ICH), Good Clinical Practice (GCP) Guidelines and with Clinical Research Organization (CRO) Standard Operating Procedures (SOPs). As part of a concerted effort to fulfill these obligations, the authorised CRO study monitor visited investigative sites prior to and during the trial in addition to maintaining telephone and written communication. Data from each subject were reviewed and source verified as the study progressed.

In accordance with audit plans, this trial may have been selected for audits. The investigators committed to permit independent audits by auditors assigned by the Sponsor at a reasonable notice. Audits included, but were not limited to, drug supply, presence of required documents, the informed consent process, protection of rights and well-being of subjects and verification of Electronic case report form (eCRF) entries against source documents.

Regulatory authorities worldwide had the right to inspect the investigative sites during or after the trial. In such cases, the investigators were required to contact the Sponsor immediately and to fully cooperate with the inspectors.

Copies of written correspondence between the investigators, CRO, Sponsor, Competent Authorities, Institutional Review Board (IRB) and Independent Ethic Committee (IEC) are on file with the Sponsor and investigators.

Adverse events were according to the Medical Dictionary for Regulatory Activities (MedDRA, version 18.0) thesaurus.

Statistical analysis were conducted according the Statistical Analysis Plan (SAP) describing the analytical principles and statistical techniques employed in order to address the objectives specified in the Protocol.

A Data Management Plan was present for missing data, to address situations where variables are reported as missing, unavailable, non-reported, uninterpretable, or considered missing because of data inconsistency or out-of-range results. ;

Related Conditions & MeSH terms

• Gout

• NCT number: NCT02500641
• Study type: Interventional
• Source: Menarini International Operations Luxembourg SA
• Status: Completed
• Phase: Phase 4
• Start date: August 17, 2015
• Completion date: May 10, 2017