Study of Verinurad in Heart Failure With Preserved Ejection Fraction
Condition: Heart Failure With Preserved Ejection Fraction (HFpEF)
MeSH terms: Heart Failure
Study type: Interventional
Phase: Phase 2

Summary: 
      International, Multicenter, Double-Blind, Placebo and Active Control Efficacy and Safety
      Study to Evaluate Verinurad combined with Allopurinol in Heart Failure with Preserved
      Ejection Fraction
    

Detailed description: 
      Evidence shows independent associations between hyperuricaemia and the risk of cardio-renal
      conditions, including heart failure (HF). Serum uric acid (sUA) is also a strong prognostic
      factor and correlates with other markers of poor prognosis in HF patients with preserved
      ejection fraction (HFpEF), and an estimated 1/2-2/3 of HFpEF patients have hyperuricaemia.
      HFpEF is a microvascular disease likely partly driven by endothelial dysfunction and
      inflammation in coronary vessel walls. Uric acid crystals have been identified in coronary
      vessel walls in some hyperuricaemic patients.

      Uric acid transporter 1 (URAT1) is responsible for reabsorption of uric acid (UA) in the
      proximal tubule. Inhibition of URAT1 results in increased urinary excretion of UA and
      lowering of uric acid in the blood. Verinurad is a novel URAT1 inhibitor in Phase 2
      development for chronic kidney disease (CKD) and HF. Verinurad combined with the xanthine
      oxidase (XO) inhibitors (XOI) febuxostat or allopurinol has been shown to lower sUA in
      patients with recurrent gout in Phase 2 studies by up to approximately 80%.

      The primary objective of this Phase 2 study is to assess the effect of a combination of
      verinurad and allopurinol on exercise capacity in patients with HFpEF.

      The secondary objectives are to assess effect of combination of verinurad and allopurinol in
      comparison to allopurinol monotheraphy on excercise capacity dwhich will be measured in peak
      VO2 as well as effect of verinurad and allopurinol compared to placebo and to allopurinol
      monotheraphy on Kansas City cardiomyopathy questionnaire (KCCQ)-total symptom score (TSS). A
      sub-study aims to investigate the relationship between UA crystals and inflammation.
    

Intervention name(s): Verinurad; Allopurinol; Placebo for verinurad; Placebo for allopurinol
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): The treatment will be titrated in 3 steps for target low dose (3 mg), intermediate dose (7.5 mg) and high dose (12mg) of verinurad.
Drug: Allopurinol The treatment will be titrated in 3 steps. Low dose (100mg), intermediate (200mg) and high dose (300mg) of allopurinol.; Study treatments will be titrated in 3 steps: Low dose (100mg), intermediate (200mg) and high dose (300mg) of allopurinol; Matching Capsule; Matching tablet
Other intervention name(s): verinurad titration 3 - 7.5 - 12mg; allopurinol titration 100 - 200 - 300 mg; allopurinol titration 100 - 200 - 300 mg; Placebo; Placebo
Intervention MeSH terms: Allopurinol; Verinurad
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Phase 2,; Double-Blind,; Placebo and Active Control,; Verinurad,; Allopurinol,; HFpEF,; Heart Failure