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Microvascular AnginaPhase 2PRIZENCT04097314

Precision Medicine With Zibotentan in Microvascular Angina

A Phase 2 study testing Zibotentan in people with Microvascular Angina, run by NHS Greater Glasgow and Clyde at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Microvascular angina (MVA) is caused by abnormalities of the small vessels in the heart. Endothelin is a small chemical that circulates and accumulates in the blood vessel walls, causing them to narrow or go into spasm and thicken in the longer term especially as levels of endothelin increase. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Microvascular Angina
What is being tested?
Zibotentan
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
225 participants
Where
1 siteUnited Kingdom
Study dates
18 Oct 2019to 8 Jun 2023
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age >18 years.
  • Microvascular angina - as defined by COVADIS diagnostic criteria for microvascular angina.
  • Able to comply with study procedures.
  • Written informed consent.

Who cannot join

  • Exercise tolerance >540 seconds in men and >430 seconds in women (i.e. actual exercise duration (s) achieved on the Bruce protocol commensurate with predicted), or, lack of anginal symptoms and/or ST-segment depression (0.1 mV) limiting exercise.
  • Non-cardiovascular exercise-limiting problem e.g. morbid (or severe) obesity (BMI ≥40.0 kg/m2)
  • Genotype not available
  • Women who are pregnant, breast-feeding or of child-bearing potential (WoCBP) without a negative pregnancy test and who are unwilling or unable to follow the reproductive restrictions and use highly effective contraception as defined in Appendix 3 of the protocol for the duration of the study treatment and 30 days after last dose of study drug.
  • Men who are sexually active with a WoCBP who are unwilling to use condoms or other highly effective methods of contraception for the duration of study treatment and for 14 weeks after last dose of study drug.
  • Heart failure (New York Heart Association Grade ≥II i.e. mild symptoms and slight limitation during ordinary activity)
Show all 11Show fewer
  • Recent (<3 months) myocardial infarction
  • A history of epilepsy, other CNS adverse events, neurologic symptoms or signs consistent with spinal cord compression or CNS metastases.
  • Moderate or more severe renal impairment (GFR < 45 mL/min)
  • Liver disease with a Child-Pugh score of A (5-6 points) or higher
  • Participation in another intervention study involving a drug within the past 90 days or 5 half-lives whichever is longer (co-enrolment in observational studies is permitted).

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

  • NHS Greater Glasgow and Clyde

    Glasgow

Other trials in United Kingdom

About this study

Official title: A Randomised, Double-blind, Placebo-controlled, Cross-over Trial of Zibotentan in Microvascular Angina

Microvascular angina (MVA) is caused by abnormalities of the small vessels in the heart. Endothelin is a small chemical that circulates and accumulates in the blood vessel walls, causing them to narrow or go into spasm and thicken in the longer term especially as levels of endothelin increase. As a result, patients experience pain, psychological burden and an inability to carry out daily activities.

Originally developed by AstraZeneca for cancer treatment, prior research has confirmed that Zibotentan relaxes the small blood vessels of patients with MVA which lends support to the idea that Zibotentan may bring some benefits to patients with MVA. This trial therefore proposes to look into re-purposing zibotentan as a new treatment for patients with MVA. The primary objective is to assess the effect of add-on treatment with Zibotentan to treadmill exercise times in adult patients with MVA and impaired exercise intolerance. Zibotentan could provide a new treatment pathway for patients, as well as be made available to the NHS at substantially lower cost than the currently used medications.

The trial aims to initially invite approx. 356 participants for genetic testing. A minimum of 100 participants will go forward into the main study, receiving either 10mg zibotentan or a dummy matched tablet (placebo) daily over two 12 weeks periods of each, completing their final visit at week 34. The study assessments will involve a health check at each visit, including information on the patient's wellbeing, blood tests, some quality of life questionnaires, and an exercise test. Participants will also have the option to consent to additional sub-study cardiovascular MRI scanning. Finally, participants will be invited to provide consent for long-term follow-up (maximum 20 years) of their electronic medical records (no additional patient contact).

Read the detailed description

The study design publication is available at https://pubmed.ncbi.nlm.nih.gov/32942043/

Being tested
Zibotentan, Placebo oral tablet
Keywords
Microvascular Angina, Angina, Endothelin, MVA, Impaired Exercise Intolerance
Medical subject headings
Microvascular Angina, Angina Pectoris

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ZibotentanDrug

    10mg OD Zibotentan

  • Placebo oral tabletDrug

    Placebo

Study groups in NCT04097314
Study groupRoleWhat they receive
ZibotentanExperimentalNot described
Receives: Drug: Zibotentan
PlaceboPlacebo comparatorNot described
Receives: Drug: Placebo oral tablet

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. EFFICACY - Exercise Testing (treadmill exercise time, seconds)

    The primary outcome is the treadmill exercise time (TET) measured in seconds using the Full Bruce protocol, a measure of aerobic capacity that reflects disease severity. A within-subject improvement in exercise time (tested at week 10 (baseline), week 22 (crossover) and week 34 (final visit)) of 30 seconds is considered clinically relevant.

    Measured: 34 weeks

Secondary outcomes (12)

  1. EFFICACY - Health Status QLQ (Seattle Angina Questionnaire)

    Seattle Angina Questionnaire (SAQ) Summary Score and component scores (Angina Limitation, Angina Stability, Angina Frequency, Treatment Satisfaction and Quality of Life) will be recorded at all study visits.

    Measured: 34 weeks

  2. EFFICACY - Health Status QLQ (Illness Perception - Brief IPQ)

    Brief Illness Perception Questionnaire (Brief IPQ), a nine-item scale designed to rapidly assess the cognitive and emotional representations of illness taken at all study visits.

    Measured: 34 weeks

  3. EFFICACY - Health Status QLQ (Anxiety/depression - PHQ4)

    The Four-Item Patient Health Questionnaire (PHQ-4) for Anxiety and Depression is a validated tool for detecting both anxiety and depressive disorders and will administered at all study visits

    Measured: 34 weeks

  4. EFFICACY - Health Status QLQ (Treatment satisfaction - TSQM)

    The 14-item Treatment Satisfaction Questionnaire for Medication (TSQM) is a reliable and valid instrument to assess patients' satisfaction with medication, providing scores on four scales - side effects, effectiveness, convenience and global satisfaction and will administered at all study visits

    Measured: 34 weeks

  5. EFFICACY - Health Status QLQ (EQ5D-5L)

    The 5-item EuroQol Group EQ5D-5L is a validated questionnaire comprising mobility, self-care, usual activities, pain/discomfort and anxiety/depression to quantitatively assess patient's self-reported health status and will be administered at each study visit.

    Measured: 34 weeks

  6. FEASIBILITY - Withdrawal Rate

    Participant withdrawal rate from study will be measured throughout.

    Measured: 34 weeks

  7. SAFETY - SAEs

    Number of Participants With Treatment-Related Adverse Events as Assessed and reported by local study teams throughout trial.

    Measured: 34 weeks

  8. EFFICACY - Exercise Testing (time,sec to 1mm ST-depression)

    Within-subject improvements in time (seconds) to 1 mm ST-depression during exercise tolerance testing will be assessed using the Full Bruce protocol. Assessments will be during screening, week 10 (baseline), week 22 (crossover) and week 34 (final visit).

    Measured: 34 weeks

  9. EFFICACY - Exercise Testing (maximum ST-segment deviation, mV)

    Within-subject improvements in maximum ST-segment deviation (mV) during exercise tolerance testing will be assessed using the Full Bruce protocol. Assessments will be during screening, week 10 (baseline), week 22 (crossover) and week 34 (final visit).

    Measured: 34 weeks

  10. EFFICACY - Exercise Testing (Time (s) to 75% of max age-related heart rate during exercise)

    Within-subject improvements in time (seconds) to 75% of max age-related heart rate during exercise tolerance testing will be assessed using the Full Bruce protocol. Assessments will be during screening, week 10 (baseline), week 22 (crossover) and week 34 (final visit).

    Measured: 34 weeks

  11. EFFICACY - Exercise Testing (Metabolic equivalent (METs)

    Within-subject improvements in metabolic equivalent (METs) during exercise tolerance testing will be assessed using the Full Bruce protocol. Assessments will be during screening, week 10 (baseline), week 22 (crossover) and week 34 (final visit). The resting metabolic rate is defined as 3.5 ml O2/kg/min (METs).

    Measured: 34 weeks

  12. EFFICACY - Exercise Testing (DUKE Score)

    Within-subject improvements in Duke treadmill score (DTS) during exercise tolerance testing will be assessed using the Full Bruce protocol. Assessments will be during screening, week 10 (baseline), week 22 (crossover) and week 34 (final visit). Duke treadmill score is defined as maximum exercise time in minutes - (5 × the maximal net ST-segment deviation in mm during or after exercise) - (4 × the treadmill angina index (where 0 = no angina, 1 = non-limiting angina, 2 = exercise limiting angina).

    Measured: 34 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Sep 2019
  2. Study start18 Oct 2019
  3. Primary completion8 Jun 2023
  4. Study completion8 Jun 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
225 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04097314
Sponsor's protocol ID
GN18CA068
Acronym
PRIZE
Status last verified
Apr 2023
First submitted
5 Jul 2019
Last updated
4 Aug 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Morrow A, Young R, Abraham GR, Hoole S, Oliveira JMG, Greenwood JP, Arnold JR, Ferreira V, Rakhit R, Galasko G, Sinha A, Perera D, Al-Lamee R, Spyridopoulos I, Kotecha A, Clesham G, Ford TJ, Davenport A, Padmanabhan S, Kaski JC, Weir RA, Sattar N, Ambery P, Welsh P, McConnachie A, Berry C; PRIZE Study Group. Exercise treadmill testing for efficacy evaluation in randomized, controlled trials. Am Heart J. 2026 Jul;297:107379. doi: 10.1016/j.ahj.2026.107379. Epub 2026 Feb 11.

    PubMed 41687797

  • Morrow A, Young R, Abraham GR, Hoole S, Greenwood JP, Arnold JR, El Shibly M, Shanmuganathan M, Ferreira V, Rakhit R, Galasko G, Sinha A, Perera D, Al-Lamee R, Spyridopoulos I, Kotecha A, Clesham G, Ford TJ, Davenport A, Padmanabhan S, Jolly L, Kellman P, Kaski JC, Weir RA, Sattar N, Kennedy J, Macfarlane PW, Welsh P, McConnachie A, Berry C; PRIZE Study Group. Zibotentan in Microvascular Angina: A Randomized, Placebo-Controlled, Crossover Trial. Circulation. 2024 Nov 19;150(21):1671-1683. doi: 10.1161/CIRCULATIONAHA.124.069901. Epub 2024 Sep 1.

    PubMed 39217504

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Zibotentan in people with Microvascular Angina, run by NHS Greater Glasgow and Clyde at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

EFFICACY - Exercise Testing (treadmill exercise time, seconds) (time frame: 34 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04097314, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Aug 2023; AzTrials last refreshed its copy on 6 Nov 2026.

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