CRD-102 for Right Heart Failure in Patients With Left Ventricular Assist Devices

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.

Study Overview

• Status: Completed
• Conditions: Right Heart Failure; Left Ventricular Assist Device
• Intervention / Treatment: Drug: CRD-102

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.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CRD-102 Treatment; CRD102 Treatment	Drug: CRD-102; 14 mg CRD-102 capsules administered twice daily orally for 14 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety: Subject incidence of adverse events	Number of adverse events as a measure of safety and tolerability.	40 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory: Pulmonary artery pressures (mmHg).	Changes compared to baseline in Pulmonary artery pressures (mmHg)	40 days
Exploratory: Left ventricular ejection fraction (%)	Changes compared to baseline in left ventricular ejection fraction (%)	40 days
Exploratory: Quality of life (KCCQ questionnaire)	Changes compared to baseline in Quality of life (KCCQ questionnaire)	40 days

Collaborators and Investigators

• Sponsor: Cardiora Pty. Ltd.
• Investigators: Study Chair: David Kaye, MD PhD, Cardiora Pty. Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): March 6, 2018
• Primary Completion (Actual): October 10, 2018
• Study Completion (Actual): May 30, 2019

Study Registration Dates

• First Submitted: July 5, 2017
• First Submitted That Met QC Criteria: July 11, 2017
• First Posted (Actual): July 14, 2017

Study Record Updates

• Last Update Posted (Actual): June 25, 2019
• Last Update Submitted That Met QC Criteria: June 24, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: CARD-LV01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No