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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04327024




Registration number
NCT04327024
Ethics application status
Date submitted
13/03/2020
Date registered
30/03/2020

Titles & IDs
Public title
Study of Verinurad in Heart Failure With Preserved Ejection Fraction
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
Secondary ID [1] 0 0
2019-004862-16
Secondary ID [2] 0 0
D5496C00005
Universal Trial Number (UTN)
Trial acronym
AMETHYST
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Heart Failure With Preserved Ejection Fraction (HFpEF) 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Coronary heart disease
Cardiovascular 0 0 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
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
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline at Week 32 in Peak V02 Consumption in Verinurad + Allopurinol Compared to Placebo (ANCOVA Model)
Timepoint [1] 0 0
From baseline to Week 32
Secondary outcome [1] 0 0
Change From Baseline at Week 32 in Peak V02 Consumption in Verinurad+ Allopurinol Compared to Allopurinol Monotherapy (ANCOVA Model)
Timepoint [1] 0 0
From baseline to Week 32
Secondary outcome [2] 0 0
Change From Baseline at Week 32 in KCCQ-TSS in Verinurad+ Allopurinol Compared to Placebo (MMRM)
Timepoint [2] 0 0
From baseline to Week 22 and Week 32
Secondary outcome [3] 0 0
Change From Baseline at Week 32 in KCCQ-TSS in Verinurad+ Allopurinol Compared to Allopurinol Monotherapy (MMRM)
Timepoint [3] 0 0
From baseline to Week 22 and Week 32

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
Minimum age
40 Years
Maximum age
130 Years
Sex
Both males and females
Can healthy volunteers participate?
No
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
19/05/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
29/04/2022
Sample size
Target
Accrual to date
Final
159
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Bedford Park
Recruitment hospital [2] 0 0
Research Site - Chermside
Recruitment hospital [3] 0 0
Research Site - Geelong
Recruitment hospital [4] 0 0
Research Site - Milton
Recruitment postcode(s) [1] 0 0
5042 - Bedford Park
Recruitment postcode(s) [2] 0 0
4032 - Chermside
Recruitment postcode(s) [3] 0 0
3220 - Geelong
Recruitment postcode(s) [4] 0 0
4064 - Milton
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
North Carolina
Country [4] 0 0
United States of America
State/province [4] 0 0
Virginia
Country [5] 0 0
Argentina
State/province [5] 0 0
Caba
Country [6] 0 0
Argentina
State/province [6] 0 0
Mar del Plata
Country [7] 0 0
Argentina
State/province [7] 0 0
Rosario
Country [8] 0 0
Austria
State/province [8] 0 0
Graz
Country [9] 0 0
Austria
State/province [9] 0 0
Wien
Country [10] 0 0
Bulgaria
State/province [10] 0 0
Plovdiv
Country [11] 0 0
Bulgaria
State/province [11] 0 0
Sofia
Country [12] 0 0
Canada
State/province [12] 0 0
Quebec
Country [13] 0 0
Germany
State/province [13] 0 0
Bad Oeynhausen
Country [14] 0 0
Germany
State/province [14] 0 0
Berlin
Country [15] 0 0
Germany
State/province [15] 0 0
Göttingen
Country [16] 0 0
Germany
State/province [16] 0 0
Regensburg
Country [17] 0 0
Germany
State/province [17] 0 0
Würzburg
Country [18] 0 0
Korea, Republic of
State/province [18] 0 0
Cheongju-si
Country [19] 0 0
Korea, Republic of
State/province [19] 0 0
Gangwon-do
Country [20] 0 0
Korea, Republic of
State/province [20] 0 0
Seoul
Country [21] 0 0
Mexico
State/province [21] 0 0
Querétaro
Country [22] 0 0
Poland
State/province [22] 0 0
Bydgoszcz
Country [23] 0 0
Poland
State/province [23] 0 0
Chojnice
Country [24] 0 0
Poland
State/province [24] 0 0
Chrzanów
Country [25] 0 0
Poland
State/province [25] 0 0
Lublin
Country [26] 0 0
Poland
State/province [26] 0 0
Tychy
Country [27] 0 0
Poland
State/province [27] 0 0
Warszawa
Country [28] 0 0
Russian Federation
State/province [28] 0 0
Aramil
Country [29] 0 0
Russian Federation
State/province [29] 0 0
Kemerovo
Country [30] 0 0
Russian Federation
State/province [30] 0 0
Novosibirsk
Country [31] 0 0
Russian Federation
State/province [31] 0 0
Saint-Petersburg
Country [32] 0 0
Russian Federation
State/province [32] 0 0
St Petersburg
Country [33] 0 0
Russian Federation
State/province [33] 0 0
Tomsk
Country [34] 0 0
Slovakia
State/province [34] 0 0
Brezno
Country [35] 0 0
Slovakia
State/province [35] 0 0
Lucenec
Country [36] 0 0
Slovakia
State/province [36] 0 0
Presov
Country [37] 0 0
Slovakia
State/province [37] 0 0
Svidnik

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AstraZeneca
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Dalane Kitzman, MD
Address 0 0
1326 Riverview Road Ext Lexington, NC 27292-1764 USA
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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

Supporting document/s available: Study protocol, Statistical analysis plan (SAP)
When will data be available (start and end dates)?
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.
Available to whom?
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.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://astrazenecagroup-dt.pharmacm.com/DT/Home


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04327024