E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Fluid overload in heart failure |
Overvulling in hartfalen |
|
E.1.1.1 | Medical condition in easily understood language |
Fluid overload in heart failure |
Overvulling in hartfalen |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the effects of 80mg of furosemide delivered by subcutaneous delivery in the abdominal area over 5 hours when compared to oral administration in patients with heart failure with chronic fluid overload. |
|
E.2.2 | Secondary objectives of the trial |
To assess the effects of the furosemide regimen on natriuresis
To assess the effects on signs and symptoms of heart failure (e.g. dyspnea)
To investigate if furosemide induced diuresis correlates with changes in bioimpedance parameters
To investigate if pretreatment bioimpedance measurements predict diuretic response to furosemide
To investigate injection site reactions and discomfort during sc administration
To obtain plasma samples for pharmacokinetic analyses |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Written informed consent must be 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
Participant must have been on oral furosemide 40 mg qd or bid for a period 90 days
History of chronic heart failure with presence of moderate symptoms of decompensation. DHF is defined as presence of signs and symptoms of heart failure, like dyspnea at rest 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 pg/mL)
In the opinion of the investigator, able to participate in the study |
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E.4 | Principal exclusion criteria |
Contraindication to furosemide
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant
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 mEq/L and Serum potassium < 3.0 mEq/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
Diagnosed with diabetes mellitus requiring pharmacotherapy
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 < 15mL/min/1.73 m2, calculated using the simplified Modification of Diet in Renal Disease (sMDRD) equation
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
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E.5 End points |
E.5.1 | Primary end point(s) |
Diuresis - time to first void, volume of first void, 6-hour diuresis, 8-hour diuresis |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
6 hour following start of administration
8 hour following start of administration |
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E.5.2 | Secondary end point(s) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
6 hour following start of administration
8 hour following start of administration |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
Last observation in last subject. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |