Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
LOGIN
CREATE ACCOUNT
LOGIN
CREATE ACCOUNT
MY TRIALS
REGISTER TRIAL
FAQs
HINTS AND TIPS
DEFINITIONS
Trial Review
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this
information for consumers
Download to PDF
Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT04327024
Registration number
NCT04327024
Ethics application status
Date submitted
13/03/2020
Date registered
30/03/2020
Date last updated
29/06/2023
Titles & IDs
Public title
Study of Verinurad in Heart Failure With Preserved Ejection Fraction
Query!
Scientific title
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
Query!
Secondary ID [1]
0
0
2019-004862-16
Query!
Secondary ID [2]
0
0
D5496C00005
Query!
Universal Trial Number (UTN)
Query!
Trial acronym
AMETHYST
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
Heart Failure With Preserved Ejection Fraction (HFpEF)
0
0
Query!
Condition category
Condition code
Cardiovascular
0
0
0
0
Query!
Coronary heart disease
Query!
Cardiovascular
0
0
0
0
Query!
Other cardiovascular diseases
Query!
Intervention/exposure
Study type
Interventional
Query!
Description of intervention(s) / exposure
Treatment: Drugs - Verinurad
Treatment: Drugs - Allopurinol
Treatment: Drugs - Placebo for verinurad
Treatment: Drugs - Placebo for allopurinol
Experimental: Verinurad 12 + allopurinol - Dose [mg] verinurad/allopurinol:
Step 1 - titration_3/100 Step 2 - titration_7.5/200 Step 3 - target dose 12/300
Experimental: Allopurinol alone - Dose [mg] verinurad/allopurinol:
Step 1 - titration_0/100 Step 2 - titration_0/200 Step 3 - target dose 0/300
Placebo Comparator: Placebo - Placebo [mg] in 3 steps 0/0
Treatment: Drugs: Verinurad
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.
Treatment: Drugs: Allopurinol
Study treatments will be titrated in 3 steps: Low dose (100mg), intermediate (200mg) and high dose (300mg) of allopurinol
Treatment: Drugs: Placebo for verinurad
Matching Capsule
Treatment: Drugs: Placebo for allopurinol
Matching tablet
Query!
Intervention code [1]
0
0
Treatment: Drugs
Query!
Comparator / control treatment
Query!
Control group
Query!
Outcomes
Primary outcome [1]
0
0
Change From Baseline at Week 32 in Peak V02 Consumption in Verinurad + Allopurinol Compared to Placebo (ANCOVA Model)
Query!
Assessment method [1]
0
0
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.
Query!
Timepoint [1]
0
0
From baseline to Week 32
Query!
Secondary outcome [1]
0
0
Change From Baseline at Week 32 in Peak V02 Consumption in Verinurad+ Allopurinol Compared to Allopurinol Monotherapy (ANCOVA Model)
Query!
Assessment method [1]
0
0
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 allopurinol) = 0 Ha: Difference in mean change from baseline in peak VO2 (verinurad + allopurinol vs allopurinol) ? 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.
Query!
Timepoint [1]
0
0
From baseline to Week 32
Query!
Secondary outcome [2]
0
0
Change From Baseline at Week 32 in KCCQ-TSS in Verinurad+ Allopurinol Compared to Placebo (MMRM)
Query!
Assessment method [2]
0
0
The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a 23-item assessment that measures the patient's perception of their health status, which includes heart failure-related symptoms (frequency, burden, recent change), impact on physical and social function, self-efficacy and knowledge, and how the patient's heart failure affects their quality of life. The Total Symptom Score (TSS) averages the frequency domain and the symptom burden domain subscales, which each range from 0 to 100. The TSS ranges from 0-100 (higher scores = better health status).
Mean change from baseline in KCCQ-TSS at Week 32 between the treatment groups was compared using MMRM analysis, with change from baseline (i.e., week 32 value - baseline value) as the dependent variable, treatment as the independent variable and visit, visit by treatment, and baseline KCCQ-TSS included as covariates.
The number analyzed at each timepoint represents the number of subjects with data at each visit.
Query!
Timepoint [2]
0
0
From baseline to Week 22 and Week 32
Query!
Secondary outcome [3]
0
0
Change From Baseline at Week 32 in KCCQ-TSS in Verinurad+ Allopurinol Compared to Allopurinol Monotherapy (MMRM)
Query!
Assessment method [3]
0
0
The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a 23-item assessment that measures the patient's perception of their health status, which includes heart failure-related symptoms (frequency, burden, recent change), impact on physical and social function, self-efficacy and knowledge, and how the patient's heart failure affects their quality of life. The Total Symptom Score (TSS) averages the frequency domain and the symptom burden domain subscales, which each range from 0 to 100. The TSS ranges from 0-100 (higher scores = better health status).
Mean change from baseline in KCCQ-TSS at Week 32 between the treatment groups was compared using MMRM analysis, with change from baseline (i.e., week 32 value - baseline value) as the dependent variable, treatment as the independent variable and visit, visit by treatment, and baseline KCCQ-TSS included as covariates.
The number analyzed at each timepoint represents the number of subjects with data at each visit.
Query!
Timepoint [3]
0
0
From baseline to Week 22 and Week 32
Query!
Eligibility
Key inclusion criteria
- 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:
1. Have NYHA functional class II-III at enrolment
2. Have medical history of typical symptoms/signs of HF > 6 weeks before enrolment
3. LVEF = 45%
4. 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
Query!
Minimum age
40
Years
Query!
Query!
Maximum age
130
Years
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
Key exclusion criteria
- 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.
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Randomised controlled trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Blinded (masking used)
Query!
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people analysing the results/data
Query!
Query!
Query!
Query!
Intervention assignment
Parallel
Query!
Other design features
Query!
Phase
Phase 2
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Completed
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
19/05/2020
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
Query!
Actual
29/04/2022
Query!
Sample size
Target
Query!
Accrual to date
Query!
Final
159
Query!
Recruitment in Australia
Recruitment state(s)
Query!
Recruitment hospital [1]
0
0
Research Site - Bedford Park
Query!
Recruitment hospital [2]
0
0
Research Site - Chermside
Query!
Recruitment hospital [3]
0
0
Research Site - Geelong
Query!
Recruitment hospital [4]
0
0
Research Site - Milton
Query!
Recruitment postcode(s) [1]
0
0
5042 - Bedford Park
Query!
Recruitment postcode(s) [2]
0
0
4032 - Chermside
Query!
Recruitment postcode(s) [3]
0
0
3220 - Geelong
Query!
Recruitment postcode(s) [4]
0
0
4064 - Milton
Query!
Recruitment outside Australia
Country [1]
0
0
United States of America
Query!
State/province [1]
0
0
California
Query!
Country [2]
0
0
United States of America
Query!
State/province [2]
0
0
Florida
Query!
Country [3]
0
0
United States of America
Query!
State/province [3]
0
0
North Carolina
Query!
Country [4]
0
0
United States of America
Query!
State/province [4]
0
0
Virginia
Query!
Country [5]
0
0
Argentina
Query!
State/province [5]
0
0
Caba
Query!
Country [6]
0
0
Argentina
Query!
State/province [6]
0
0
Mar del Plata
Query!
Country [7]
0
0
Argentina
Query!
State/province [7]
0
0
Rosario
Query!
Country [8]
0
0
Austria
Query!
State/province [8]
0
0
Graz
Query!
Country [9]
0
0
Austria
Query!
State/province [9]
0
0
Wien
Query!
Country [10]
0
0
Bulgaria
Query!
State/province [10]
0
0
Plovdiv
Query!
Country [11]
0
0
Bulgaria
Query!
State/province [11]
0
0
Sofia
Query!
Country [12]
0
0
Canada
Query!
State/province [12]
0
0
Quebec
Query!
Country [13]
0
0
Germany
Query!
State/province [13]
0
0
Bad Oeynhausen
Query!
Country [14]
0
0
Germany
Query!
State/province [14]
0
0
Berlin
Query!
Country [15]
0
0
Germany
Query!
State/province [15]
0
0
Göttingen
Query!
Country [16]
0
0
Germany
Query!
State/province [16]
0
0
Regensburg
Query!
Country [17]
0
0
Germany
Query!
State/province [17]
0
0
Würzburg
Query!
Country [18]
0
0
Korea, Republic of
Query!
State/province [18]
0
0
Cheongju-si
Query!
Country [19]
0
0
Korea, Republic of
Query!
State/province [19]
0
0
Gangwon-do
Query!
Country [20]
0
0
Korea, Republic of
Query!
State/province [20]
0
0
Seoul
Query!
Country [21]
0
0
Mexico
Query!
State/province [21]
0
0
Querétaro
Query!
Country [22]
0
0
Poland
Query!
State/province [22]
0
0
Bydgoszcz
Query!
Country [23]
0
0
Poland
Query!
State/province [23]
0
0
Chojnice
Query!
Country [24]
0
0
Poland
Query!
State/province [24]
0
0
Chrzanów
Query!
Country [25]
0
0
Poland
Query!
State/province [25]
0
0
Lublin
Query!
Country [26]
0
0
Poland
Query!
State/province [26]
0
0
Tychy
Query!
Country [27]
0
0
Poland
Query!
State/province [27]
0
0
Warszawa
Query!
Country [28]
0
0
Russian Federation
Query!
State/province [28]
0
0
Aramil
Query!
Country [29]
0
0
Russian Federation
Query!
State/province [29]
0
0
Kemerovo
Query!
Country [30]
0
0
Russian Federation
Query!
State/province [30]
0
0
Novosibirsk
Query!
Country [31]
0
0
Russian Federation
Query!
State/province [31]
0
0
Saint-Petersburg
Query!
Country [32]
0
0
Russian Federation
Query!
State/province [32]
0
0
St Petersburg
Query!
Country [33]
0
0
Russian Federation
Query!
State/province [33]
0
0
Tomsk
Query!
Country [34]
0
0
Slovakia
Query!
State/province [34]
0
0
Brezno
Query!
Country [35]
0
0
Slovakia
Query!
State/province [35]
0
0
Lucenec
Query!
Country [36]
0
0
Slovakia
Query!
State/province [36]
0
0
Presov
Query!
Country [37]
0
0
Slovakia
Query!
State/province [37]
0
0
Svidnik
Query!
Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Query!
Name
AstraZeneca
Query!
Address
Query!
Country
Query!
Ethics approval
Ethics application status
Query!
Summary
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
Query!
Trial website
https://clinicaltrials.gov/ct2/show/NCT04327024
Query!
Trial related presentations / publications
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
Dalane Kitzman, MD
Query!
Address
0
0
1326 Riverview Road Ext Lexington, NC 27292-1764 USA
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT04327024
Download to PDF