None listed
Conditions
Brief summary
The coronary slow flow phenomenon (CSFP) is a coronary microvascular disorder that was first clinically characterised by University of Adelaide researchers. It is defined using a coronary angiography, a x- ray like procedure where a dye is injected into the heart arteries to investigate the patency of arteries, by delayed dye opacification of the large heart arteries, reflecting the underlying increased microvascular (small arteries) resistance. Studies conducted both at the University and at other sites, have implicated Endothelin-1 (a potent microvascular vasoconstrictor) could explain the CSFP. Basing on the existing evidence, present study investigates, Zibotentan, a potent endothelin-1 receptor blocker, benefits the CSFP patients by reducing angina frequency using a randomized, double-blind, placebo-controlled, cross-over trial design.
Interventions
Zibotentan (ZD4054) (Manufacturer: AstraZeneca)
- Dose - 10mg once daily
- Duration - 8 weeks (4 weeks drug intervention and 4 weeks placebo)
- The mode of administration - oral tablet
Each subject will undergo treatment with Zibotentan and matched placebo for 4 weeks in a computer-generated random order (double-blind, crossover design) giving a total dosing period of 8 weeks. There will be a 2-week washout interval between the two treatment periods.
Patient will report the angina frequency th
Zibotentan (ZD4054) (Manufacturer: AstraZeneca) - Dose - 10mg once daily - Duration - 8 weeks (4 weeks drug intervention and 4 weeks placebo) - The mode of administration - oral tablet Each subject will undergo treatment with Zibotentan and matched placebo for 4 weeks in a computer-generated random order (double-blind, crossover design) giving a total dosing period of 8 weeks. There will be a 2-week washout interval between the two treatment periods. Patient will report the angina frequency through and angina diary. The drug compliance will be assessed through drug tablet return.
Sponsors
The University of Adelaide
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
For inclusion in the study subjects should fulfil the following criteria: I. Provision of informed consent prior to any study specific procedures II. Female or male patients aged greater than or equal to 18 years III. Documented angiographic features of coronary slow flow. as de ned by TIMI-2 flow (i.e. requiring more than 3 beats to opacify a major epicardial vessel) in the absence of obstructive coronary artery disease (i.e. no epicardial lesion greater than 50%). IV. Chest pain occurring more than or equal to 3 times/week in the preceding two weeks.
Exclusion criteria
i. Acute coronary syndrome admission within the preceding month; i.e. hospital admission for prolonged angina pain at rest associated with new ischaemic ECG changes and/or a rise in cardiac troponin level. ii. Secondary causes of the CSFP including - the no-reflow phenomenon and myocarditis. iii. Secondary causes of angina including - clinically significant anaemia (haemoglobin lesser than 100g/dL), uncontrolled atrial fibrillation (i.e. ventricular response rate greater than 108 bpm), haemodynamically significant aortic stenosis (estimated mean aortic valve gradient greater than or equal to 40mmHg). iv. Patients with known concomitant disease with life expectance of less than 1 year. v. Previous use of endothelin receptor antagonist within 3 months of the study start vi. Abnormalities in liver function tests (ALT and/or AST greater than or equal to 2 x upper limit of normal (ULN) or ALP greater than or equal to 2 x ULN or Bilirubin greater than or equal to 1.5 x ULN) vii. Patients with body weight lesser than 40Kg viii. Contraindication to any of the study treatments or known or suspected hypersensitivity to the investigational product, compounds of the same class, other study treatments or any excipients ix. Previous history of epilepsy or the other CNS AEs, neurological symptoms or signs consistent with acute or evolving spinal cord compression or CNS metastases. x. Patients with baseline EF lesser than 40% and/or New York Heart Association class III or IV heart failure xi. Patients with moderate to severe hepatic impairment xii. Patients with moderate and severe renal failure (defined as a CLCR of lesser than 50 mL/minute determined using the Cockcroft-Gaul equation or by 24-hour CLCR), including patients undergoing renal dialysis xiii. QT interval corrected for heart rate (eg, by Bazett’s correction) greater than 450msec for men and greater than 470 msec for women. xiv. Women of child-bearing potential xv. Patients with known pregnancy or who are breast-feeding. xvi. Male study participants who have a female partner of child-bearing potential and who are not willing to comply with requirements for use of contraception for the duration of the study and the specified period after the last dose of study drug. xvii. Patients with pregnant partners xviii. Patients with cancer or malignancy. xix. Current evidence of drug abuse or significant history of drug abuse, as judged by the investigator. xx. Current evidence of alcohol abuse or a significant history of alcohol abuse, as judged by the investigator. xxi. Unwilling, or unable, to give informed consent. xxii. Concomitant participation in another clinical trial or research study
Outcome results
None listed