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

Study Overview
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Brief Summary
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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.

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

Conditions
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Heart Failure

Intervention / Treatment
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* Drug: Milrinone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MIlrinone<br>ER milrinone | Drug: Milrinone<br>* Administration of study medications, PK sampling and safety profile- add on haemodynamic invasive measurements if patient consents to.<br>|

What is the study measuring?
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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 |