Precision Medicine With Zibotentan in Microvascular Angina

  • STATUS
    Recruiting
  • End date
    Nov 30, 2022
  • participants needed
    356
  • sponsor
    NHS Greater Glasgow and Clyde
Updated on 26 January 2021

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).

Description

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

Details
Condition Angina Pectoris, Angina, Cardiac syndrome X, Angina
Treatment Placebo Oral Tablet, Zibotentan
Clinical Study IdentifierNCT04097314
SponsorNHS Greater Glasgow and Clyde
Last Modified on26 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

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

Exclusion Criteria

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)
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)
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If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

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