E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Catecholamine-Resistant Hypotension |
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E.1.1.1 | Medical condition in easily understood language |
Low blood pressure that is resistant to correction by treatment with catecholamines. |
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E.1.1.2 | Therapeutic area | Body processes [G] - Circulatory and Respiratory Physiological Phenomena [G09] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10049705 |
E.1.2 | Term | Acute hypotension |
E.1.2 | System Organ Class | 10021097 - Hypotension |
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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 compare the effect of LJPC-501 infusion, versus placebo, on mean arterial pressure (MAP) in patients with catecholamine-resistant hypotension (CRH). |
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E.2.2 | Secondary objectives of the trial |
Secondary • To compare change in Sequential Organ Failure Assessment (SOFA) scores with LJPC-501 infusion, versus placebo • To establish the safety and tolerability of LJPC-501 and compare to placebo in patients with CRH Exploratory • To compare change in heart rate with LJPC-501 infusion, versus placebo • To compare change in catecholamine dosing with LJPC-501 infusion, versus placebo • To compare mortality with LJPC-501 infusion, versus placebo. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Adult patients ≥ 18 years of age with CRH, defined as those who require a total sum catecholamine dose of >0.2 mcg/kg/min for a minimum of 6 hours and a maximum of 48 hours, to maintain a MAP between 55-70 mmHg. 2. Patients are required to have central venous access and an arterial line present, and these are expected to remain present for at least the initial 48 hours of study. 3. Patients are required to have an indwelling urinary catheter present, and it is expected to remain present for at least the initial 48 hours of study. 4. Patients must have received at least 25 mL/kg of crystalloid or colloid equivalent over the previous 24-hour period, and be adequately volume resuscitated in the opinion of the treating investigator. 5. Patients must have clinical features of high-output shock by meeting one of the following criteria. a. Central venous oxygen saturation (ScvO2) > 70% (either by oximetry catheter or by central venous blood gas) and central venous pressure (CVP) > 8 mmHg. OR b. Cardiac Index (CI) > 2.3 L/min/1.73 m2. Patient must meet 5a or 5b to be eligible. 6. Patient or legal surrogate is willing and able to provide written informed consent and comply with all protocol requirements. |
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E.4 | Principal exclusion criteria |
1. Patients who are < 18 years of age. 2. Any patient with burns covering > 20% of total body surface area (TBSA). 3. Patients with a Cardiovascular (CV) SOFA score ≤ 3. 4. Patients diagnosed with acute occlusive coronary syndrome requiring intervention. 5. Patients on veno-arterial (VA) ECMO. 6. Patients who have been on ECMO for less than 12 hours. 7. Patients in liver failure with a Model for End-Stage Liver Disease (MELD) score of ≥ 30. 8. Patients with a history of asthma or who are currently experiencing bronchospasm requiring the use of inhaled bronchodilators, if not mechanically ventilated. 9. Patients with acute mesenteric ischemia or a history of mesenteric ischemic. 10. Patients with a history of, presence of, or highly-suspected of having an aortic dissection or abdominal aortic aneurysm. 11. Patients requiring more than 500 mg daily of hydrocortisone or equivalent glucocorticoid medication as a standing dose. 12. Patients with Raynaud’s phenomenon, systemic sclerosis or vasospastic disease. 13. Patients with an expected lifespan of < 12 hours. 14. Patients with active bleeding AND an anticipated need (within 48 hours of initiation of the study) for transfusion of > 4 units of packed red blood cells. 15. Patients with active bleeding AND hemoglobin < 7g/dL or any other condition that would contraindicate serial blood sampling. 16. Patients with an absolute neutrophil count (ANC) of < 1000 cells/mm3. 17. Patients with a known allergy to mannitol. 18. Patients who are current participating in another interventional clinical trial. 19. Patients who are known to be pregnant at the time of Screening |
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E.5 End points |
E.5.1 | Primary end point(s) |
To compare the effect of LJPC-501 infusion on mean arterial pressure (MAP) in patients with catecholamine- resistant hypotension (CRH). The primary efficacy endpoint is the proportion of patients with a MAP of 75 mmHg or greater or a 10 mmHg increase in baseline MAP at Hour 3. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Patients will be monitored for hemodynamic vital signs, i.e., Heart Rate (HR) and Mean Arterial Pressure (MAP) at Screening, -30, -15, and 0 minutes or just prior to initiation of study drug dosing, on Day 1 prior to every dose titration and minimally every 15 minutes during hours 0 – 3:15, and prior to any dose adjustments and minimally hourly thereafter beginning at Day 1 at hour 4 through Day 2 at 48 hours. During the first 3 hours of study drug dosing, MAP should be measured in triplicate, at least 1 minute apart and averaged to determine the current MAP for dose titrations. Evaluation of MAP will continue once daily on Days 3-7. |
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E.5.2 | Secondary end point(s) |
To compare change in Sequential Organ Failure Assessment (SOFA) scores.
To establish the safety and tolerability of LJPC-501 and compare to placebo in patients with CRH. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The change in total SOFA score between Baseline and hour 48 including a separate analysis of the CV SOFA score are secondary efficacy endpoints. The total SOFA is the sum of the 6 individual SOFA item scores including CV . The baseline SOFA will be the last measure reported for each of the SOFA items prior to initiating study drug. The hour 48 measures will be the outcome reported at the hour 48 assessment. |
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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 | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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) | 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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
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 | No |
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 |
Australia |
Belgium |
Canada |
Finland |
France |
Germany |
New Zealand |
Switzerland |
United Kingdom |
United States |
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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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End of study will be the last visit 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 | 0 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 31 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 7 |