None listed
Conditions
Brief 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.
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 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
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.
Sponsors
Flinders University
Study design
Allocation
Non-randomised trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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 criteria
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).
Outcome results
None listed