Investigation of whether a drug called azacitidine can be safely used to make patients with hypertrophic cardiomyopathy feel better
| ISRCTN | ISRCTN17069976 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN17069976 |
| Integrated Research Application System (IRAS) | 1009388 |
| Protocol serial number | 24078LD-UC |
| Sponsor | Belfast Health and Social Care Trust |
| Funders | British Heart Foundation, Innovate UK, Heart Trust Fund |
- Submission date
- 13/09/2025
- Registration date
- 15/12/2025
- Last edited
- 15/12/2025
- Recruitment status
- Not yet recruiting
- Overall study status
- Ongoing
- Condition category
- Circulatory System
Plain English summary of protocol
Background and study aims
Hypertrophic cardiomyopathy is an inherited condition that affects the heart's ability to pump blood around the body. It affects around 1 in 500 people in the UK and can lead to heart failure. For people with hypertrophic cardiomyopathy everyday tasks like walking upstairs or to the shops becomes impossible. New drugs are needed to improve the lives of people with hypertrophic cardiomyopathy to stop the disease getting worse.
In support of this, we have discovered that a process called DNA methylation, which affects how your genetic code is expressed, can change in people with heart failure and other forms of heart disease. Pre-clinical studies have shown that changes in DNA methylation in diseased hearts are reversible using low doses of a drug called azacitidine, which also improves how the heart functions.
This drug is used in other types of patients with certain cancers but has not been used before to treat hypertrophic cardiomyopathy. The aim of this project is to test the drug in hypertrophic cardiomyopathy patients for the first time, through testing a range of low doses and to select a dose to study in more detail to provide evidence on how well it works to improve patient and heart health. The long-term benefits of this research could lead to the development of a new drug type for hypertrophic cardiomyopathy.
Who can participate?
Patients aged 18 to 75 years with non-obstructive hypertrophic cardiomyopathy (nHCM)
What does the study involve?
The study will involve receiving injections of the drug twice weekly for 16 weeks, blood samples will be taken as well as some physical exams including an echocardiogram and cardiac MRI. It will take 3 years to complete, although each participant will only be involved for the 16 weeks of treatment with a 4-week follow-up.
What are the possible benefits and risks of participating?
Although this study drug is already in common use for other conditions, it is possible participants will experience unwanted or unexpected side effects related to the medication. Any side effect is recorded at each visit and will be tracked throughout the study. The doses administered in this trial will be much less than those given currently to cancer patients and therefore it is expected there will be less side effects at this dose. Nonetheless, intensive monitoring during the treatment period has been planned to minimise risk.
Some individuals may present with an allergy to the drug, these patients will be immediately taken off the drug and any symptoms will be treated accordingly. Participants will be monitored for at least 30 minutes after receiving each dose of the drug to check for any reactions such as allergy. The drug can also cause nausea and vomiting, as such anti-sickness drugs will be available for prescription to any participant who experiences this side effect. There can also be slight local reactions in the skin around the injection site such as inflammation or a rash. Injection sites will be reviewed at each site visit which will be twice-weekly and any required treatments such as antihistamines will be prescribed as required.
The greatest risk with this medication is a fall in blood counts which is why so many blood samples are required. Patients will have bloods checked before receiving any dose of the medication to make sure they are safe to begin treatment. Once treatment has started blood samples will be taken weekly and reviewed before the next week's treatment can be given to ensure it is safe for participants to continue taking the medication. As well as checking for blood counts, the blood samples will be used to monitor the health of the participants kidneys to ensure the drug is not effecting kidney function.
There are no adequate data on the use of the drug in pregnant women, therefore the potential risk for humans is unknown. Because of this, patients who are pregnant or breastfeeding will be excluded from the study and any participants are asked to use contraception throughout the study. Female participants of reproductive age will also have regular urine pregnancy tests to monitor them, if they become pregnant they will not receive anymore medication.
There is a significant time requirement from the participants in terms of having to attend the clinic twice-weekly for treatment for 16 weeks and also requiring an additional follow-up visit. Participants will be made aware of the commitment at the time of recruitment and will be reimbursed for travel and food expenses to help compensate for the efforts made by the participants.
All these risks are clearly outlined in the participant information sheet and during recruitment potential participants will have all risks clearly explained to them and be given time to discuss any concerns with the research team.
Where is the study run from?
Belfast City Hospital (UK)
When is the study starting and how long is it expected to run for?
September 2025 to January 2028
Who is funding the study?
1. British Heart Foundation (BHF)
2. Innovate UK
3. Heart Trust Fund
Who is the main contact?
1. Lana Dixon, lana.dixon@qub.ac.uk
2. Chris Watson, chris.watson@qub.ac.uk
Contact information
Scientific, Principal investigator
274 Grosvenor Road
Belfast
BT12 6BA
United Kingdom
| Phone | +44 (0)7710740876 |
|---|---|
| lana.dixon@belfasttrust.hscni.net |
Scientific
Wellcome-Wolfson Institute for Experimental Medicine
Queen's University Belfast
97 Lisburn Road
Belfast
BT9 7BL
United Kingdom
 ORCID ID |
0000-0001-8749-0732 |
|---|---|
| Phone | +44 (0)2890 976478 |
| chris.watson@qub.ac.uk |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Open randomized controlled trial |
| Secondary study design | Randomised controlled trial |
| Study type | Participant information sheet |
| Scientific title | A trial to evaluate the safety and efficacy of treatment with azacitadine in patients with symptomatic non-obstructive hypertrophic cardiomyopathy |
| Study acronym | AZTEC |
| Study objectives | The aim of this study is to conduct an exploratory Phase II clinical trial to evaluate the safety and efficacy of azacitidine in patients with symptomatic non-obstructive hypertrophic cardiomyopathy (nHCM). To explore the efficacy of 16 weeks treatment with azacitidine in HCM. |
| Ethics approval(s) |
Not yet submitted |
| Health condition(s) or problem(s) studied | Hypertrophic cardiomyopathy (HCM) |
| Intervention | Phase 2a participants will all receive azacitidine treatment, with the dose being escalated/deescalated based on the TITE-CRM DLT model. During Phase 2b participants will be randomly assigned by 1:1 allocation to either azacitidine treatment arm or usual care/best available treatment (BAT). Treatment arm: Treatment arm refers to any participants receiving the study intervention, azacitidine. This includes all participants in Phase 2a but only those allocated to the study intervention in Phase 2b. During Phase 2a participants will be allocated to receive either 5, 10, 15, 20, 25 or 30 mg/m2 dose of azacitidine, dependent on the dose escalation/de-escalation plan and recommendations from the DMEC based on the previous dose cohort. Treatment with azacitidine will be administered on a bi-weekly basis for 16 weeks. During Phase 2b participants allocated to treatment arm will receive the DMEC recommended and TMG approved dose of azacitidine as established during Phase 2a of the study. Treatment with azacitidine will be administered on a bi-weekly basis for 16 weeks. To promote patient retention and follow-up visits will be consolidated where possible and adequate compensation sought to reimburse costs for travel expenses. Usual care/best available treatment (BAT): Usual care/BAT in symptomatic nHCM is the empirical management of patient’s symptoms and complications they may develop over time. In the absence of randomised clinical trials pharmacological therapy is administered on an empirical basis to improve functional capacity and symptoms. As a comparative group for this study participants allocated to usual care/BAT arm will be reviewed on a monthly basis. Visits will be consolidated where possible and use of “remote” consultations where in person visits or data are not required will be used in order to promote participant retention and follow-up. |
| Intervention type | Drug |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Azacitidine |
| Primary outcome measure(s) |
Phase 2a: |
| Key secondary outcome measure(s) |
All measured at baseline (day 0) and at 16 weeks (day 113): |
| Completion date | 31/01/2028 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Lower age limit | 18 Years |
| Upper age limit | 75 Years |
| Sex | All |
| Target sample size at registration | 72 |
| Key inclusion criteria | 1. Age 18 to 75 years who have a diagnosis of phenotype positive nHCM consistent with current American and European guidelines; Left ventricle (LV) wall thickness ≥15 mm (or ≥13 mm with a family history of HCM). 2. Symptomatic of nHCM at screening (defined as being NYHA functional class II/III). 3. Elevated N-terminal pro-hormone of Brain Natriuretic Peptide (NT pro-BNP) level >125 pg/ml as measured within 6 months of screening. 4. Left ventricular ejection fraction (LVEF) ≥55%. 5. Left Ventricular Outflow Tract (LVOT) peak gradient at rest and during Valsalva <50mmHg as determined by the echocardiography laboratory. 6. Men who are sexually active, must agree to acceptable birth control methods whilst receiving the the study drug and until 3 months after the last dose of study drug. 7. Women of childbearing potential, must agree to acceptable birth control methods during the study and until 6 months after the last dose of study drug. |
| Key exclusion criteria | 1. Presence of any active malignancy that required treatment within the last year 2. Patient is known to be pregnant or lactating 3. Consent to participate is declined 4. Absolute contraindication to study drug 5. NYHA functional class IV 6. Patients with reduced baseline blood counts (i.e. WBC <3.0 × 109/L or ANC <1.5 × 109/L or platelets <75.0 × 109/L) prior to the first treatment 7. Patient is enrolled in another investigational drug study within the past 6 months 8. Patient is incapable of completing exercise stress test |
| Date of first enrolment | 01/02/2026 |
| Date of final enrolment | 01/12/2026 |
Locations
Countries of recruitment
- United Kingdom
- Northern Ireland
Study participating centre
Belfast
BT9 7AB
Northern Ireland
Results and Publications
| Individual participant data (IPD) Intention to share | Yes |
|---|---|
| IPD sharing plan summary | Available on request |
| IPD sharing plan | The datasets generated and/or analysed during the current study will be available upon request following the publication of the primary and secondary outcomes. Formal requests for data should be made in writing to Dr Lana Dixon (Chief Investigator) via the Northern Ireland Clinical Trials Unit (the trial co-ordinating centre) at AZTEC@nictu.hscni.net Requests will be reviewed on a case-by-case basis in collaboration with the Sponsor. The study will comply with the good practice principles for sharing individual participant data from publicly funded clinical trials and data sharing will be undertaken in accordance with the required regulatory requirements. Following the publication of the primary and secondary outcomes, any requests for data will need to be made in writing to the Chief investigator via the CTU, who will liaise with the Sponsor and obtain approval for the release of the data. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
Editorial Notes
13/12/2025: ISRCTN received notification of combined HRA/MHRA approval for this trial on 13/12/2025.
15/09/2025: Study's existence confirmed by the HRA.
