Study of Verinurad in Heart Failure With Preserved Ejection Fraction
AMETHYST
A Phase 2, Multicentre, Double-Blind, Placebo and Active Control Efficacy and Safety Study to Evaluate Verinurad Combined With Allopurinol in Heart Failure With Preserved Ejection Fraction
2 other identifiers
interventional
159
11 countries
56
Brief 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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started May 2020
56 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 13, 2020
CompletedFirst Posted
Study publicly available on registry
March 30, 2020
CompletedStudy Start
First participant enrolled
May 19, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 29, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
April 29, 2022
CompletedResults Posted
Study results publicly available
June 29, 2023
CompletedJune 29, 2023
June 1, 2023
1.9 years
March 13, 2020
April 26, 2023
June 12, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Change From Baseline at Week 32 in Peak V02 Consumption in Verinurad + Allopurinol Compared to Placebo (ANCOVA Model)
Mean change from baseline in peak VO2 at Week 32 between the treatment groups was compared using change from baseline (i.e., week 32 value - baseline value) as the dependent variable, treatment as the independent variable and baseline peak VO2 included as covariate. H0: Difference in mean change from baseline in peak VO2 (verinurad + allopurinol vs placebo) = 0 Ha: Difference in mean change from baseline in peak VO2 (verinurad + allopurinol vs placebo) ≠ 0 A hierarchical test sequence was used for the confirmatory analysis of the primary and secondary objectives in order to address the issue of multiple testing and control the Type I error rate at an overall two-sided 0.05 level. Since this was the first test in the hierarchical test sequence and endpoint was not rejected at a two-sided 0.05 level, the testing sequence did not continue.
From baseline to Week 32
Secondary Outcomes (3)
Change From Baseline at Week 32 in Peak V02 Consumption in Verinurad+ Allopurinol Compared to Allopurinol Monotherapy (ANCOVA Model)
From baseline to Week 32
Change From Baseline at Week 32 in KCCQ-TSS in Verinurad+ Allopurinol Compared to Placebo (MMRM)
From baseline to Week 22 and Week 32
Change From Baseline at Week 32 in KCCQ-TSS in Verinurad+ Allopurinol Compared to Allopurinol Monotherapy (MMRM)
From baseline to Week 22 and Week 32
Study Arms (3)
Verinurad 12 + allopurinol
EXPERIMENTALDose \[mg\] verinurad/allopurinol: Step 1 - titration\_3/100 Step 2 - titration\_7.5/200 Step 3 - target dose 12/300
Allopurinol alone
EXPERIMENTALDose \[mg\] verinurad/allopurinol: Step 1 - titration\_0/100 Step 2 - titration\_0/200 Step 3 - target dose 0/300
Placebo
PLACEBO COMPARATORPlacebo \[mg\] in 3 steps 0/0
Interventions
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
Eligibility Criteria
You may qualify if:
- Patient must be ≥ 40 years of age at the time of signing the ICF
- Patients with hyperuricaemia defined as sUA level of \> 6 mg/dL.
- Patients with documented diagnosis of symptomatic HFpEF according to all of the following criteria:
- Have NYHA functional class II-III at enrolment
- Have medical history of typical symptoms/signs of HF \> 6 weeks before enrolment
- LVEF ≥ 45%
- NT-proBNP ≥ 125 pg/mL (≥ 14.75 pmol/L) at Visit 1 for patients without ongoing atrial fibrillation/flutter.
- Patients able to exercise to near exhaustion during a CPET as exhibited by RER
- ≥ 1.05 during CPET conducted during screening. If patient does not achieve RER ≥ 1.05 the CPET may be repeated once, at least 48 hours but less than 2 weeks (but before randomisation) after the initial test; in such cases the second test will serve as baseline.
- Male or female
You may not qualify if:
- eGFR \< 30ml/min/1.73m2 (based on CKD-EPI formula)
- Presence of any condition that precludes exercise testing
- Known history of a documented LVEF \< 40%
- Probable alternative or concomitant diagnoses which in the opinion of the Investigator could account for the patient's HF symptoms and signs (eg, anaemia, hypothyroidism)
- Known carrier of the Human Leukocyte Antigen-B (HLA-B) \*58:01 allele: HLA-B
- \*58:01 genotyping is mandatory prior to randomization for all patients.
- Patients diagnosed with tumor lysis syndrome or Lesch-Nyhan syndrome
- Patients who are severely physically or mentally incapacitated and who in the opinion of investigator are unable to perform the patients' tasks associated with the protocol
- Presence of any condition which, in the opinion of the investigator, places the patient at undue risk or potentially jeopardises the quality of the data to be generated
- Current acute decompensated HF or hospitalisation due to decompensated HF \< 4 weeks prior to enrolment
- Myocardial infarction, unstable angina, coronary revascularisation (percutaneous coronary intervention or coronary artery bypass grafting), ablation of atrial flutter/fibrillation, valve repair/replacement, implantation of a cardiac resynchronisation therapy device, stroke or transient ischemic attack within 6 months prior to enrolment.
- Planned coronary revascularisation, ablation of atrial flutter/fibrillation and/or valve repair/replacement
- Atrial fibrillation with persistent resting heart rate \> 110 beats per minute.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
Study Sites (58)
Research Site
Granada Hills, California, 91344, United States
Research Site
Northridge, California, 91324, United States
Research Site
Torrance, California, 90502, United States
Research Site
Miami, Florida, 33135, United States
Research Site
Pembroke Pines, Florida, 33024, United States
Research Site
Port Orange, Florida, 32127, United States
Research Site
Winston-Salem, North Carolina, 27157, United States
Research Site
Norfolk, Virginia, 23510, United States
Research Site
CABA, C1006ACC, Argentina
Research Site
CABA, C1119ACN, Argentina
Research Site
CABA, C1425AGC, Argentina
Research Site
Mar del Plata, 7600, Argentina
Research Site
Mar del Plata, B7600GNY, Argentina
Research Site
Rosario, 2000, Argentina
Research Site
Bedford Park, 5042, Australia
Research Site
Chermside, 4032, Australia
Research Site
Geelong, 3220, Australia
Research Site
Milton, 4064, Australia
Research Site
Graz, 8036, Austria
Research Site
Vienna, 1090, Austria
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Plovdiv, 4004, Bulgaria
Research Site
Sofia, 1000, Bulgaria
Research Site
Sofia, 1431, Bulgaria
Research Site
Québec, Quebec, G1G 3Y8, Canada
Research Site
Québec, Quebec, G1V 4G5, Canada
Research Site
Québec, Quebec, G2J 0C4, Canada
Research Site
Québec, Quebec, G3K 2P8, Canada
Research Site
Bad Oeynhausen, 32545, Germany
Research Site
Berlin, 10789, Germany
Research Site
Berlin, 13353, Germany
Research Site
Göttingen, 37075, Germany
Research Site
Regensburg, 93053, Germany
Research Site
Würzburg, 97078, Germany
Research Site
Querétaro, 76000, Mexico
Research Site
Bydgoszcz, 85-079, Poland
Research Site
Chojnice, 89-600, Poland
Research Site
Chrzanów, 32-500, Poland
Research Site
Lublin, 20-362, Poland
Research Site
Tychy, 43-100, Poland
Research Site
Warsaw, 02-097, Poland
Research Site
Warsaw, 02-637, Poland
Research Site
Warsaw, 04-628, Poland
Research Site
Aramil, 624002, Russia
Research Site
Kemerovo, 650002, Russia
Research Site
Novosibirsk, 630055, Russia
Research Site
Saint Petersburg, 195067, Russia
Research Site
Saint Petersburg, 199226, Russia
Research Site
Tomsk, 634012, Russia
Research Site
Brezno, 97742, Slovakia
Research Site
Lučenec, 984 01, Slovakia
Research Site
Prešov, 080 01, Slovakia
Research Site
Svidník, 08901, Slovakia
Research Site
Cheongju-si, 28644, South Korea
Research Site
Gangwon-do, 26426, South Korea
Research Site
Seoul, 03080, South Korea
Research Site
Seoul, 03722, South Korea
Research Site
Seoul, 05505, South Korea
Research Site
Seoul, 08308, South Korea
Related Publications (1)
Kitzman DW, Voors AA, Mentz RJ, Lewis GD, Perl S, Myte R, Kaguthi G, Sjostrom CD, Kallgren C, Shah SJ. Verinurad Plus Allopurinol for Heart Failure With Preserved Ejection Fraction: The AMETHYST Randomized Clinical Trial. JAMA Cardiol. 2024 Oct 1;9(10):892-900. doi: 10.1001/jamacardio.2024.2435.
PMID: 39141378DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Global Clinical Lead
- Organization
- AstraZeneca Clinical Study Information Center
Study Officials
- PRINCIPAL INVESTIGATOR
Dalane Kitzman, MD
1326 Riverview Road Ext Lexington, NC 27292-1764 USA
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 13, 2020
First Posted
March 30, 2020
Study Start
May 19, 2020
Primary Completion
April 29, 2022
Study Completion
April 29, 2022
Last Updated
June 29, 2023
Results First Posted
June 29, 2023
Record last verified: 2023-06
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
- Access Criteria
- When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared