Left Ventricular Assist Device, Right Heart Failure
Conditions
Brief summary
This is a Phase 1b/IIa, single centre, non-randomised open-label uncontrolled study to assess safety, effect and PK of oral CRD-102 in patients with RHF associated with the presence of an LVAD.
Detailed description
The study will be conducted over a 40 day time period inclusive of screening and follow up time periods. Eligible subjects will receive oral CRD-102 for 14 days.
Interventions
DRUGCRD-102
14 mg CRD-102 capsules administered twice daily orally for 14 days.
Sponsors
Cardiora Pty. Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
Patients are enrolled only if they met the following criteria. 1. Males and females aged 18-85 years inclusive 2. Have received a LVAD (HeartWare HVAD, HeartMate II) at least 30 days prior to screening. 3. Stable LVAD patients with evidence of ongoing right heart failure as evidenced by raised right atrial pressure indicated by JVP \>6cm OR measured right atrial pressure ≥12mmHg within the 3 months prior to or at Baseline OR dilated IVC on echocardiography PLUS all of the following; 1. ongoing diuretic therapy; 2. echocardiography in the 3 months prior to or at Baseline showing at least mild impairment in overall RV systolic function by visual assessment together with a TAPSE \< 14mm. 4. Able to give written informed consent and agree to adhere to all protocol requirements. 5. All patients will be required to have an implanted cardiaoverter defibrillator. (ICD)
Exclusion criteria
1. Hemodynamically unstable patients. 2. Hypotension (MAP\<60 or systolic BP \<90 mmHg) at Screening or Baseline 3. Hypertension (MAP\>95 or systolic BP \>130 mmHg) at Screening or Baseline 4. Ventricular tachycardia or ventricular fibrillation in the past 30 days or poorly controlled atrial fibrillation (ventricular rate \>120 bpm) 5. Concurrent participation in another investigational device study or prior participation in which a device was implanted and remains in place 6. Receipt of any investigational research agent within 30 days or 5 half-lives (whichever is longer) prior to Baseline. 7. Current treatment with intravenous inotropes or levosimendan, or treatment within the 2 weeks prior to Screening 8. Significant renal (eGFR\<25 ml/min/1.73 sq m) or hepatic (bilirubin \>3mg/dL) impairment or anemia (Hb \<90g/dL) at Screening or Baseline. 9. Expected heart transplantation within the study period. 10. Pregnancy 11. History of allergic reaction to milrinone or any excipients in the study drug.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety: Subject incidence of adverse events | 40 days | Number of adverse events as a measure of safety and tolerability. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory: Pulmonary artery pressures (mmHg). | 40 days | Changes compared to baseline in Pulmonary artery pressures (mmHg) |
| Exploratory: Left ventricular ejection fraction (%) | 40 days | Changes compared to baseline in left ventricular ejection fraction (%) |
| Exploratory: Quality of life (KCCQ questionnaire) | 40 days | Changes compared to baseline in Quality of life (KCCQ questionnaire) |
Countries
United States
Outcome results
None listed