A Method Validation Study for Evaluation of Novel Treatments Limiting Pulmonary Oedema in Cardiac Failure

This is an interventional basic science trial for Heart Failure, Congestive focused on measuring Acute decompensated heart failure, heart failure, MRI, trpV4 channel inhibitors, pulmonary oedema Read More

Inclusion Criteria:

• Male or females over 18 years of age at the time of signing the informed consent.
• Body weight >=50 kilogram (kg) and Body Mass Index (BMI) within the range 18.0-40.0 kilogram/square meter (kg/m^2) (inclusive).
• Able to understand and comply with protocol requirements, instructions and protocol stated restrictions and is willing to take part in the imaging sessions.
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

Inclusion Criteria for Heart Failure Group (group 2) - Established diagnosis of mild to moderate heart failure of any aetiology with symptoms defined as corresponding to the New York Heart Association (NYHA) class II or III.

Inclusion Criteria for Healthy Volunteer Group (group 1)

- Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, brief physical examination, clinical laboratory tests, and Electrocardiogram (ECG).

Inclusion Criteria for Subjects with ADHF (Group 3)

• Male subjects OR female subjects of non reproductive potential as defined as pre-menopausal females with a documented tubal ligation or hysterectomy, or post-menopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 million international units (MIU)/millilitre (mL) and oestradiol < 40picogram (pg)/mL (< 140 pmol/L) is confirmatory.
• 50 years of age or over at the time of signing the informed consent
• Hospitalized for the management of acute decompensated HF
• Presence of dyspnoea at rest or with minimal activity
• Presence of at least one of the following signs: Tachypnea with respiratory rate >=20 breaths/min or Rales or crackles audible on auscultation
• Chest x-ray with evidence of pulmonary congestion/oedema performed approximately within the last 48 hours (if not available - an additional research CXR may be requested)
• Have received at least one treatment with an intravenous diuretic prior to the first MRI scan
• Body weight >= 50kg and BMI within the range 18-40 kg/m^2 (inclusive)
• Able to understand and comply with protocol requirements, instructions and protocol-stated restrictions and is willing to take part in the imaging sessions
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form

Exclusion criteria:

Exclusion Criteria for Heart Failure Group

• History of known primary pulmonary disease requiring current medication or other therapy.
• Orthopnoea of sufficient severity to preclude supine scanning as determined at screening.
• Unstable angina within the past 3 months.
• Uncontrolled hypertension (resting systolic Blood Pressure (BP) >160 millimeters of mercury (mmHg) or resting diastolic BP >100 mmHg).
• Resting hypoxia while breathing room air (Saturation of Oxygen [SaO2] <88%). Exclusion Criteria for Healthy Volunteer Group and Heart Failure Groups
• Current smoker, defined as having smoked in the preceding 6 months.
• Contraindication for MRI scanning (as assessed by local MRI safety questionnaire) which includes but not limited to: Intracranial aneurysm clips or other metallic objects; Intra-orbital metal fragments that have not been removed ; Pacemakers or other implanted cardiac rhythm management devices and non-MRI compatible heart valves; Inner ear implants; and History of claustrophobia.
• Pregnant females as determined by positive urine human chorionic gonadotropin (HCG) test at screening or any scanning session.
• Positive test for drugs of abuse, not due to current prescription drugs as determined by the GSK Medical Monitor and principal investigator (PI), and alcohol screen.
• Estimated Creatinine Clearance (Cockcroft-Gault) <60 millilitre (mL)/minute.

Exclusion Criteria for Subjects with ADHF (Group 3)

• End-stage heart failure defined as requiring left ventricular assist devices, intra-aortic balloon pump or any type of mechanical support
• Chronic or intermittent renal support therapy (hemodialysis, ultrafiltration, or peritoneal dialysis)
• Ongoing or planned intravenous diuretic treatment within 1 hour of MRI scan appointment
• History of known primary pulmonary disease requiring current medication or other therapy
• Orthopnoea of sufficient severity to preclude supine scanning (as determined by a 15-minute test of lying supine with or without the use of oxygen)
• Contraindication for MRI scanning (as assessed by local MRI safety questionnaire), which includes but is not limited to: Intracranial aneurysm clips (except Sugita) or other metallic objects OR intra-orbital metal fragments that have not been removed OR pacemakers or other implanted cardiac rhythm management devices and non-MRI compatible heart valves OR inner ear implants OR history of claustrophobia
• Estimated creatinine clearance (Cockcroft-Gault) <40mL/minute
• Contraindication to MRI contrast agents
• Previous inclusion in a research and/or medical protocol involving nuclear medicine, PET or radiological investigations with significant radiation burden(a significant radiation burden being defined as 10 millisieverts (mSv) in addition to natural background radiation, in the previous 3 years including the dose from this study).