Clinical trial NCT03217331: CRD-102 for Right Heart Failure in Patients With Left Ventricular Assist Devices
Official title: CRD-102 for Right Heart Failure in Patients With Left Ventricular Assist Devices
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Right Heart Failure
Left Ventricular Assist Device
Lead sponsor: Cardiora Pty. Ltd.
Sponsor class: INDUSTRY
First posted: 2017-07-14
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Safety: Subject incidence of adverse events
timeFrame: 40 days
Secondary outcomes:
Other outcomes:
measure: Exploratory: Pulmonary artery pressures (mmHg).
timeFrame: 40 days
measure: Exploratory: Left ventricular ejection fraction (%)
timeFrame: 40 days
measure: Exploratory: Quality of life (KCCQ questionnaire)
timeFrame: 40 days
Locations:
city: Chicago
country: United States
facility: The University of Chicago Medical Center
state: Illinois
Study officials:
affiliation: Cardiora Pty. Ltd.
name: David Kaye, MD PhD
role: STUDY_CHAIR
References: