Precision Medicine With Zibotentan in Microvascular Angina

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. 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).

Conditions

• Microvascular Angina

Interventions

DRUG

Zibotentan

10mg OD Zibotentan

DRUG

Placebo oral tablet

Placebo

Sponsors & Collaborators

• University of Glasgow

  collaborator OTHER

• King's College London

  collaborator OTHER

• University of Oxford

  collaborator OTHER

• Oxford University Hospitals NHS Trust

  collaborator OTHER

• University of Cambridge

  collaborator OTHER

• Papworth Hospital NHS Foundation Trust

  collaborator OTHER_GOV

• Blackpool Teaching Hospitals NHS Foundation Trust

  collaborator OTHER

• Royal Free Hospital NHS Foundation Trust

  collaborator OTHER

• AstraZeneca

  collaborator INDUSTRY

• Siemens Healthcare Ltd

  collaborator UNKNOWN

• NHS Greater Glasgow and Clyde

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-10-18

Primary Completion

2023-06-08

Completion

2023-06-08

Countries

• United Kingdom

Study Locations