RecruitingPhase 4ACTRN12614000461695

Assessment of the Effects of Cardiopulmonary Phenotype on Oral and intravenous (IV) Frusemide Pharmacokinetics

An investigation of the change in concentration time profile for the diuretic drug frusemide when administered orally and intravenously to individuals with oedema associated with pulmonary hypertension or compensated and decompensated congestive heart failure.

Sponsor

Flinders University

Enrollment

20 participants

Start Date

May 5, 2014

Study Type

Interventional

Conditions

Congestive Heart Failure Pulmonary Hypertension

Summary

While there is currently a paucity of evidence to guide this practice, frusemide is routinely administered IV to patients presenting to Flinders Medical Centre (FMC) with either decompensated heart failure or pulmonary hypertension on the basis that expert opinion considers oral frusemide ineffective for managing these conditions. This study will assess the impact of congestive cardiac failure (acutely decompensated and compensated) and pulmonary hypertension on the oral and intravenous (IV) pharmacokinetics of frusemide, and determine whether altered pharmacokinetics may explain the variability and perceived lack of efficacy of oral frusemide in managing these conditions. It is hypothesised that these conditions will differentially affect the rate of oral frusemide absorption (i.e. the time to maximal concentration / response will be delayed), but that neither will affect the extent of absorption (i.e. bioavailability will remain unchanged). By improving the understanding of the impact of these conditions on frusemide pharmacokinetics, this study will form a framework to facilitate future research here at FMC to deliver more personalised and optimised dosing of frusemide that may combine oral and IV routes of administration, which will provide more effective management of symptoms, while reducing the time to hospital discharge.

Eligibility

Sex: Both males and femalesMin Age: 18 Yearss

Inclusion Criteria12

Adult males and females over the age of 18 years being treated for either acutely decompensated congestive heart failure or pulmonary hypertension by the appropriate physician specialists.
Potential study participants will be enrolled into the respective arms of the study (acutely decompensated congestive heart failure or pulmonary hypertension) on the basis of clinician assessment of the following variables:
Acutely decompensated congestive heart failure referred from the cardiology clinic:
Documented reduced ejection fraction (<45%).
Presence of at least one symptom (dyspnoea, orthopnoea, fatigue or oedema) and
Presence of at least one sign (rales, peripheral oedema, ascites, or pulmonary vascular congestion on chest radiography) of heart failure.
Pulmonary hypertension referred from the pulmonary hypertension clinic and requiring frusemide to alleviate the congestion caused by right heart failure:
Documented elevation of pulmonary arterial pressures (either noninvasively by echocardiogram or invasively by right heart catheterization) >25 mmHg
Documented normal ejection fraction (>50%), and
Presence of at least one sign (lower limb oedema or ascites) of pulmonary hypertension.
Compensated heart failure will be recognised by:
The assessment of the treating clinical team but should include: improvement of the principal symptom and improvement in signs of decompensated CHF

Exclusion Criteria1

Clinical symptoms: systolic blood pressure of less than 90mmHg, serum creatinine level >300microg/L, co-administered intravenous vasodilators or inotropic agents (other than digoxin). Documented ischaemic heart disease or systemic hypertension (pulmonary hypertension group only).

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Interventions

On Day 1, in patients that are clinically considered be suffering from oedema secondary to acutely decompensated congestive heart failure or pulmonary hypertension, following the administration of an

On Day 1, in patients that are clinically considered be suffering from oedema secondary to acutely decompensated congestive heart failure or pulmonary hypertension, following the administration of an IV bolus dose of frusemide (typically 40mg), a series of blood (5mL) and urine samples will be collected at t= 0, 1, 2, 3, 4, 5 and 6hrs for analysis of frusemide concentrations. On Day 2 (acutely decompensated phase) following the administration of an oral bolus dose of frusemide (double the Day 1 IV dose; typically 80mg), a series of blood (5mL) and urine samples will be collected at t= 0, 1, 2, 3, 4, 5 and 6hrs for analysis of frusemide concentrations. In patients presenting with oedema secondary to acutely decompensated heart failure, five to seven days later, on Day E-1 when the patient is clinically considered to no longer be acutely decompensated (i.e. they have returned to compensated heart failure) following the administration of an IV bolus dose of frusemide (typically 40mg), a series of blood (5mL) and urine samples will be collected at t= 0, 1, 2, 3, 4, 5 and 6hrs for analysis of frusemide concentrations. On Day E (compensated phase) following the administration of an oral bolus dose of frusemide (double the Day E-1 IV dose; typically 80mg), a series of blood (5mL) and urine samples will be collected at t= 0, 1, 2, 3, 4, 5 and 6hrs for analysis of frusemide concentrations.