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Trial registered on ANZCTR


Registration number
ACTRN12614000461695
Ethics application status
Approved
Date submitted
30/04/2014
Date registered
2/05/2014
Date last updated
22/10/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
Assessment of the Effects of Cardiopulmonary Phenotype on Oral and intravenous (IV) Frusemide Pharmacokinetics
Scientific title
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.
Secondary ID [1] 284510 0
Nil
Universal Trial Number (UTN)
Trial acronym
iCOFD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Congestive Heart Failure 291769 0
Pulmonary Hypertension 291784 0
Condition category
Condition code
Cardiovascular 292127 292127 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 289268 0
Treatment: Drugs
Comparator / control treatment
Nil
Control group
Uncontrolled

Outcomes
Primary outcome [1] 292006 0
The change in blood and urine concentrations-time profiles for frusemide following oral administration in patients during decompensated- and compensated- congestive heart failure.
Timepoint [1] 292006 0
Sampling will occur hourly 6 hours following oral frusemide administration.
Primary outcome [2] 292007 0
The change in blood and urine concentrations-time profiles for frusemide following intravenous administration in patients during decompensated- and compensated- congestive heart failure.
Timepoint [2] 292007 0
Sampling will occur hourly for 6 hours following intravenous frusemide administration.
Secondary outcome [1] 307986 0
The impact on blood and urine concentrations-time profiles for frusemide following oral administration in patients with oedema secondary to pulmonary hypertension.
Timepoint [1] 307986 0
Sampling will occur hourly for 6 hours following oral frusemide administration
Secondary outcome [2] 307987 0
The impact on blood and urine concentrations-time profiles for frusemide following intravenous administration in patients with oedema secondary to pulmonary hypertension.
Timepoint [2] 307987 0
Sampling will occur hourly for 6 hours following intravenous frusemide administration

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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).

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
5/05/2014
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 2371 0
Flinders Medical Centre - Bedford Park
Recruitment postcode(s) [1] 8036 0
5042 - Bedford Park

Funding & Sponsors
Funding source category [1] 289150 0
University
Name [1] 289150 0
Flinders University
Country [1] 289150 0
Australia
Primary sponsor type
University
Name
Flinders University
Address
Flinders Drive
Bedford Park
South Australia 5042
Country
Australia
Secondary sponsor category [1] 287816 0
None
Name [1] 287816 0
Address [1] 287816 0
Country [1] 287816 0
Other collaborator category [1] 277926 0
Hospital
Name [1] 277926 0
Flinders Medical Centre
Address [1] 277926 0
Flinders Drive
Bedford Park
South Australia 5042
Country [1] 277926 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290923 0
Southern Adelaide Clinical Human Research Ethics Committee
Ethics committee address [1] 290923 0
Flinders Medical Center
Flinders Drive
Bedford Park
South Australia 5042
Ethics committee country [1] 290923 0
Australia
Date submitted for ethics approval [1] 290923 0
Approval date [1] 290923 0
24/03/2014
Ethics approval number [1] 290923 0
HREC/14/SAC/28

Summary
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.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 48010 0
Dr Andrew Rowland
Address 48010 0
Department of Clinical Pharmacology Flinders Medical Centre Flinders Drive Bedford Park South Australia 5042
Country 48010 0
Australia
Phone 48010 0
+61 8 8204 7546
Fax 48010 0
Email 48010 0
[email protected]
Contact person for public queries
Name 48011 0
Dr Maneesha Dedigama
Address 48011 0
Department of Clinical Pharmacology Flinders Medical Centre Flinders Drive Bedford Park South Australia 5042
Country 48011 0
Australia
Phone 48011 0
+61 8 8204 5202
Fax 48011 0
Email 48011 0
[email protected]
Contact person for scientific queries
Name 48012 0
Dr Patrick Russell
Address 48012 0
Department of General Medicine Flinders Medical Centre Flinders Drive Bedford Park South Australia 5042
Country 48012 0
Australia
Phone 48012 0
+61 8 8204 5511
Fax 48012 0
Email 48012 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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