None listed
Conditions
Brief summary
Heart failure is a condition where the heart’s pumping cycle does not function as it should. There are two types of heart failure, with about half of patients with the condition falling into each group. One where the pump/contraction function of the heart is reduced. That is called systolic heart failure. In the other type, the heart does not fully relax, so it does not fill properly with blood. This is called diastolic heart failure or “heart failure with normal pump function”. The official medical term is “heart failure with preserved ejection fraction”, and is abbreviated as HFPEF. At the moment, there are no established medical therapies for HFPEF. Our research has shown that people with HFPEF develop breathlessness very quickly during physical activity because the heart muscle cannot relax normally. In this study we want to test the effect of a medicine, CRD-102, on the pressure in the heart during exercise in HFPEF patients. The use of CRD-102 tablets in this study is considered experimental. CRD-102 tablets have not been approved for marketing by the Therapeutics Goods Administration (TGA) in Australia. Because of its actions on the heart we hope that it may be helpful in patients with diastolic heart failure.
Interventions
Administration of CRD-102 vs placebo, with a two week placebo run in period.
Day one - all participants will commence oral administration of one placebo capsule, identical in appearance to CRD-102, twice daily for 14 day duration, at which point 1:1 randomisation will occur, 50% of participants will continue to take the placebo capsule twice daily while the other 50% will take one 14mg oral capsule of CRD-102 twice daily (12 hourly) days 15 - 42. The study will run for 43 days (+/-3 days). All
Administration of CRD-102 vs placebo, with a two week placebo run in period. Day one - all participants will commence oral administration of one placebo capsule, identical in appearance to CRD-102, twice daily for 14 day duration, at which point 1:1 randomisation will occur, 50% of participants will continue to take the placebo capsule twice daily while the other 50% will take one 14mg oral capsule of CRD-102 twice daily (12 hourly) days 15 - 42. The study will run for 43 days (+/-3 days). All empty medication containers will be collected and returned to pharmacy for accountability and to monitor adherence, as well as a participant diary, which will be given to participants to record any missed dosed etc.
Sponsors
Cardiora pty Ltd
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subject is willing and able to provide informed consent 2. Subject is willing and able to comply to all protocol requirements and procedures, including visits 3. Males and Females 18 years of age or older 4. Patients with symptoms of heart failure (NYHA III) 5. LVEF>40% at screening 6. HF Hospitalisation within 12 months or NT-BNP>400pg/mL (in SR) or NT-BNP>600pg/mL (in AF) 7. Septal E/e’>12 and <20 8. Left atrial volume index >28ml/m2 9. Stable medical therapy including diuretics for 2 weeks If subject is female of childbearing potential, the subject agrees to use an accepted form of contraception throughout the study, including follow-up. (Women who are post-menopausal for at least 2 years or are surgically sterile are not considered to be of childbearing potential.)
Exclusion criteria
1. Subject has had a myocardial infarct (MI) within 90 days before Screening 2. Subject is listed for heart transplant or a LVAD 3. Subject has a systolic blood pressure less than 90 mm Hg at time of screening 4. Subject has undergone cardiac surgery within the 60 days before screening 5. Subject is suspected of having symptoms primarily related to pericardial disease as suggested by relevant imaging or hemodynamic features 6. Subject has a moderate or greater degree of cardiac valvular stenosis or regurgitation 7. Subject has, at screening, clinically significant hepatic disease (serum total bilirubin equal to 3.0 mg/dL [= 51.3 micromol/L]), renal disease (eGFR less than 30 mL/min), or hematologic, gastrointestinal, immunologic, endocrine, metabolic, or central nervous system disease 8. Subject is symptomatically too unwell to be considered for trial, as evidenced by 6MWT less than 150m 9. Symptomatic ventricular arrhythmia or ICD firing within 90 days before screening 10. Poorly controlled atrial fibrillation (resting heart rate greater than 100 bpm) 11. Subjects who are receiving flecainide, encainide, propafenone, dofetilide, or disopyramide up to 2 weeks prior to screening 12. Subjects who have received within 7 days before the Screening or dosing visits: a. An IV positive inotropic agent b. A human B-type natriuretic peptide, including nesiritide c. An oral or IV phosphodiesterase III inhibitor (PDEI III), including levosimendan and cilostazol 13. Subjects who have the following laboratory results at screening a. Serum potassium concentration less than 4.0 or greater than 5.5 mEq/L b. Serum magnesium concentration less than 1.0 mEq/L c. Serum digoxin concentration less than 1.2 ng/mL 14. Female subjects who are pregnant and/or lactating
Outcome results
None listed