Pilot Study of Slow Release Oral Milrinone in Patients With Advanced Heart Failure

Advanced heart failure (HF), ineffective pumping of the heart, is a common, life-threatening cardiovascular disorder, characterised by marked symptomatic limitation and frequent hospitalization. It is particularly prevalent in older individuals (up to 10% of the population) and it has become the most common cause for hospitalization in people >65yrs. As such it is also one of the leading consumers of healthcare spending. Recurrent hospitalization is frequently due in significant part to the lack of viable therapeutic options for severe HF. During hospital admission, medications through a drip to give through a vein (intravenous therapy), is required to improve heart pumping capacity (such as milrinone).They are frequently used and in many cases prolonged treatment periods of intravenous therapy are required. In a growing number of cases, there is a need to continue this treatment at home, however this is particularly costly and often complicated by intravenous line infection. As such there is an expanding need for therapeutic options in patients with advanced HF. Over 20 years ago, studies of the potential utility of a rapid release form of oral milrinone were examined, however these studies demonstrated adverse effects due to its quick release.

This study aims to determine the safety and tolerability of slow release oral milrinone in advanced HF patients with no further clinical option and to evaluate its effects on HF status.

Study Overview

• Status: Completed
• Conditions: Heart Failure
• Intervention / Treatment: Drug: Milrinone

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Alfred Hospital

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:

• Advanced HF (current inpatients) with no further clinical options as defined by treating cardiologist.
• NYHA III-IV
• LVEF<35%
• Recurrent hospitalization (>/=3 admissions in the preceding 12 months) for HF
• On optimal tolerated medical/device therapy. Stable therapy for 48hrs.
• Age 18-85 yrs
• Provide written informed consent prior to any study procedure and agree to adhere to all protocol requirements

Exclusion Criteria:

• Hypotension (BPsys<85)
• Unstable rhythm including frequent non-sustained ventricular tachycardia or poorly controlled atrial fibrillation (ventricular rate >100).
• Severe renal impairment Cr>250umol/L or dialysis.
• Other life-threatening eg neoplastic, haematological, hepatic or pulmonary disease.
• Pregnancy or female with childbearing potential and inability to use contraception

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: MIlrinone; ER milrinone	Drug: Milrinone; Administration of study medications, PK sampling and safety profile- add on haemodynamic invasive measurements if patient consents to.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability	Number of MACE events change from basline safety profile bloods (Full Blood Count, urea and creatine, Liver function counts) Change in haemodynamic measurements ECG and Blood pressure and HR Monitoring Swan Ganz insertion for haemodynamic measurements (RA volume , RVSP, CO, PA, PAWP)	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NYHA Class	Change in Heart Failure Status	3 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
6 minute walk test	Change in exercise capacity	3 month
BNP		3 month
Number of Heart Failure Hospitalisation		3 months

Collaborators and Investigators

• Sponsor: The Alfred

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2013
• Primary Completion (Actual): May 10, 2017
• Study Completion (Actual): May 10, 2018

Study Registration Dates

• First Submitted: September 25, 2013
• First Submitted That Met QC Criteria: October 1, 2013
• First Posted (Estimate): October 8, 2013

Study Record Updates

• Last Update Posted (Actual): January 11, 2019
• Last Update Submitted That Met QC Criteria: January 9, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Protective Agents; Cardiotonic Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 3 Inhibitors; Milrinone
• Other Study ID Numbers: DK-MIL-2

Plan for Individual participant data (IPD)

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