E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
acute heart failure and elevated BP (systolic blood pressure [SBP] ≥160 mm Hg) requiring parenteral IV antihypertensive therapy |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000803 |
E.1.2 | Term | Acute heart failure |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020772 |
E.1.2 | Term | Hypertension |
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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 evaluate the efficacy and safety of an intravenous (IV) infusion of clevidipine as compared with standard of care (SOC) IV antihypertensive for blood pressure (BP) lowering in patients with acute heart failure (AHF) and elevated BP. |
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E.2.2 | Secondary objectives of the trial |
Exploratory objectives are to evaluate the effects on fluid balance, diuretic use and renal function and the evaluation of health economic parameters and resource utilization with clevidipine as compared to SOC IV antihypertensive treatment. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
An additional sub study will explore the relationship between inflammatory markers (myeloperoxidase [MPO] and tryptase) and clinical outcomes. This will be completed in the US only. |
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E.3 | Principal inclusion criteria |
1. Age 18 years or older 2. Presentation consistent with AHF and pulmonary congestion on physical examination as evidenced by rales. 3. Baseline SBP (immediately prior to initiation of study drug) of ≥160 mm Hg 4. Dyspnea score (sitting) of at least 5 on a 10 cm visual analog scale (VAS) 5. Requires IV antihypertensive therapy to lower BP 6. Written informed consent before initiation of any study related procedures
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E.4 | Principal exclusion criteria |
1. Administration of an agent (IV or oral) for the treatment of elevated BP within the previous 2 hours of randomization. (Previous short acting non- IV nitrates, CPAP and BiPAP are permitted) 2. Chest pain and/or electrocardiogram (ECG) with ST segment changes consistent with acute coronary syndrom. 3. Known or suspected aortic dissection 4. Acute Myocardial Infarction (AMI) within the prior 14 days 5. Dialysis dependant renal failure 6. Requirement for immediate endotracheal intubation 7. Positive pregnancy test, known pregnancy or breast feeding female 8. Intolerance or allergy to calcium channel blockers 9. Allergy to soybean oil or egg lecithin 10. Known liver failure, cirrhosis or pancreatitis 11. Prior directives against advanced life support (no code status) 12. Participation in other clinical research studies involving the evaluation of other investigational drugs or devices within 30 days of enrollment
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E.5 End points |
E.5.1 | Primary end point(s) |
Median time and percent of patients that attain the initial prespecified systolic blood pressure (SBP) target range (minimum of 20 mm Hg and a maximum of 40 mm Hg apart) and a 15% reduction in SBP from baseline within the first 30 minutes |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Yes |
E.8.1.6 | Cross over | No |
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.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
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
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The end of the trial is defined by the last visit of the last subject, which occurs 30 days following randomization of the 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 | |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 11 |