- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02350725
Furosemide Pharmacodynamics and Pharmacokinetics After Subcutaneous or Oral Administration (FUROPHARM-HF)
June 25, 2018 updated by: scPharmaceuticals, Inc.
A Single Center, Randomized, Open-label, Cross-over Exploratory Study to Evaluate the Pharmacodynamic and Pharmacokinetic Response to a Subcutaneous Administration or Oral Administration of Furosemide in Subjects With Heart Failure Presenting With Chronic Fluid Overload
The purpose of this pilot study is to investigate the pharmacodynamic and pharmacokinetic parameters of a novel furosemide formulation administered subcutaneously as compared to oral furosemide.
Study Overview
Status
Completed
Conditions
Study Type
Interventional
Enrollment (Actual)
10
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
Groningen, Netherlands
- University Medical Center Groningen
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Written informed consent obtained before any assessment is performed
- Male and female subjects ≥18 years of age, with body weight <120 kg and body mass index (BMI) <30 kg/m2
- Female subjects must be at least 2 years post-menopausal
- Participant must have been on oral furosemide (40 mg oid or bid) or therapeutic equivalent (bumetanide 1 mg oid or bid) for a period 90 days before the first dose of study medication
- History of chronic heart failure according to 2012 ESC guidelines with presence of moderate symptoms of chronic fluid overload. Chronic fluid overload is defined as presence of stable signs and symptoms of heart failure and congestion, like dyspnea at mild exertion or minimal exertion, pulmonary congestion and/or peripheral edema at the time of presentation in combination with elevated levels on natriuretic peptides (NT-proBNP > 300 ng/L)
- In the opinion of the investigator, able to participate in the study
Exclusion Criteria:
- Acute Decompensated Heart Failure (ADHF) or recent history of ADHF or significant worsening in their HF symptoms (within prior 2 weeks)
- Contraindication to furosemide
- Systolic BP (SBP) < 90 mm Hg
- Temperature > 38°C (oral or equivalent) or sepsis or active infection requiring i.v. anti-microbial treatment
- Serum sodium < 130 mmol/L and Serum potassium < 3.0 mmol/L
- Current or planned (throughout the completion of study drug infusion) treatment with any i.v. therapies, including inotropic agents, vasopressors, levosimendan, nesiritide or analogues; or mechanical support (intra-aortic balloon pump, endotracheal intubation, mechanical ventilation, or any ventricular assist device)
- History of gastric or intestinal surgery that may affect absorption of oral medication
- Presence or need for urinary catheterization
- Current or planned ultrafiltration, hemofiltration, or dialysis
- Impaired renal function defined as an estimated glomerular filtration rate (eGFR) on admission < 30 mL/min/1.73 m2 will be calculated as per standard at local laboratory
- Administration of intravenous radiographic contrast agent within 72 hours prior to screening or acute contrast-induced nephropathy at the time of screening
- Major surgery within 30 days prior to screening
- Administration of an investigational drug or implantation of investigational device, or participation in another trial, within 30 days before screening
- Inability to follow instructions or comply with procedures
- Any surgical or medical condition which in the opinion of the investigator may interfere with participation in the study or which may affect the outcome of the study
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: CROSSOVER
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Group 1
Furosemide injection solution for subcutaneous administration (80 mg) over 5 hours followed by Oral Furosemide tablets (80 mg) in second period.
|
|
EXPERIMENTAL: Group 2
Oral Furosemide tablets (80 mg) followed by Furosemide injection solution for subcutaneous administration (80 mg) over 5 hours in second period.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Diuresis and natriuresis
Time Frame: 8 hours
|
Statistical summaries with a graphical presentation will show mean and individual diuresis and natriuresis time profiles such as time to first void, volume of first void, diuresis and natriuresis measured at 60 minute intervals up to 480 minutes following furosemide injection solution for subcutaneous administration or oral tablets.
The diuretic response will be compared between therapies using t-tests or Wilcoxon test.
|
8 hours
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Body Water Content
Time Frame: 8 hours
|
The correlation (Pearson coefficient) between bioimpedance (body water content) and diuresis will be investigated including bioimpedance measurement of fluid overload as a predictor diuretic response.
|
8 hours
|
Pharmacokinetic profiles
Time Frame: 8 hours
|
A graphical presentation showing mean and individual plasma furosemide concentration-time profiles for comparison between subcutaneous or oral administration.
Plasma furosemide concentration-time data will be analyzed using a non-compartmental method and population PK approach (non-linear mixed-effect model).
Furosemide concentrations will be summarized using descriptive statistics (including N, mean, standard deviation (SD), coefficient of variation (CV%), median, minimum and maximum) for each treatment.
|
8 hours
|
Cardiac Markers (NTpro-BNP, hs-Trop T, galectin-3)
Time Frame: 8 hours
|
Correlation methods to investigate interaction between cardiac makers (NTpro-BNP, hs-Trop T, galectin-3) and pharmacodynamic parameters (diuresis and natriuresis).
|
8 hours
|
Dypsnea Scores on Visual Analog Scale and Likert Scale
Time Frame: 8 hours
|
Dyspnea score (Dyspnea Visual Analog Scale and Likert Scale), the New York Heart Association (NYHA) Functional Classification and thirst distress and grading assessments by subjects in response to subcutaneous or oral administration.
|
8 hours
|
Injection site reaction on Draize Scale and Visual Analog Pain Scale
Time Frame: 8 hours
|
Visual inspection of injection site, 5-point Draize Scale and Visual Analog pain assessment recorded during subcutaneous administration.
|
8 hours
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Rudolf A. de Boer, MD, PhD, University Medical Center Groningen
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
December 1, 2014
Primary Completion (ACTUAL)
June 1, 2015
Study Completion (ACTUAL)
June 1, 2015
Study Registration Dates
First Submitted
December 9, 2014
First Submitted That Met QC Criteria
January 26, 2015
First Posted (ESTIMATE)
January 30, 2015
Study Record Updates
Last Update Posted (ACTUAL)
June 27, 2018
Last Update Submitted That Met QC Criteria
June 25, 2018
Last Verified
December 1, 2014
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- SCP-01-001
- 2014-002546-49 (EUDRACT_NUMBER)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Heart Failure
-
Tufts Medical CenterMetro West Medical CenterCompletedCongestive Heart Failure | Diastolic Heart Failure | Systolic Heart FailureUnited States
-
Abbott Medical DevicesCompletedHeart Failure | Heart Failure, Diastolic | Heart Failure, Systolic | Heart Failure NYHA Class II | Heart Failure NYHA Class III | Heart Failure With Reduced Ejection Fraction | Heart Failure NYHA Class IV | Heart Failure With Normal Ejection Fraction | Heart Failure; With Decompensation | Heart Failure...United States, Canada
-
Manipal UniversityUnknownHeart Failure | Decompensated Heart Failure | Acute Heart Failure | Diastolic Heart Failure | Systolic Heart FailureIndia
-
University Hospital, MontpellierCompletedHeart Failure | Diastolic Heart Failure | Systolic Heart Failure Stage CFrance
-
VA Eastern Colorado Health Care SystemNational Institute on Aging (NIA)CompletedHeart Failure | Heart Failure, Diastolic | Heart Failure, Systolic | Heart Failure With Reduced Ejection Fraction | Heart Failure With Preserved Ejection Fraction | Heart Failure; With Decompensation | Heart Failure,Congestive | Heart Failure AcuteUnited States
-
Lancaster General HospitalLouise von Hess Medical Research InstituteEnrolling by invitationDiastolic Heart FailureUnited States
-
Wake Forest UniversityCompletedHeart Failure, Congestive | Heart Failure With Preserved Ejection Fraction
-
Wake Forest UniversityNational Institute on Aging (NIA)CompletedHeart Failure, Congestive | Diastolic Heart FailureUnited States
-
Giresun UniversityIstanbul University - Cerrahpasa (IUC)RecruitingHeart Failure | Diastolic Heart Failure | Systolic Heart FailureTurkey
-
US Department of Veterans AffairsCompleted
Clinical Trials on Furosemide injection solution for subcutaneous administration (80 mg)
-
SQ Innovation, Inc.Accel Clinical ServicesCompleted
-
scPharmaceuticals, Inc.Completed
-
Geisinger ClinicTerminatedObesity | Diabetic Kidney Disease | Type 2 Diabetes Mellitus in Obese | CKD | Severe ObesityUnited States
-
University of AlbertaOctapharmaRecruitingPrimary Immune Deficiency Disorder | Secondary Immune DeficiencyCanada
-
Almirall, S.A.Completed
-
Fundación Instituto de Estudios de Ciencias de...Instituto de Investigación Biomédica de SalamancaCompletedLaparoscopic CholecystectomySpain
-
Biomedica Foscama S.p.A. Industria Chimico-FarmaceuticaNot yet recruiting
-
Vista KlinikNovartisTerminatedNeovascular Age-related Macular DegenerationSwitzerland
-
Leonardo ClavijoAmgenUnknownPeripheral Arterial DiseaseUnited States
-
Neupharma SrlSintesi Research Srl; Pari Pharma GmbH; AptuitCompleted