Brief Summary
This is a Phase 3, double-blind, randomized study of LJPC-501 (angiotensin II) in adult patients diagnosed with catecholamine-resistant hypotension (CRH) conducted in multiple centers globally.
Brief Title
A Phase 3 Study of LJPC-501 in Patients With Catecholamine-Resistant Hypotension
Detailed Description
Catecholamine-resistant hypotension (CRH) is an often fatal condition resulting from an underlying cause such as septic shock, inflammation due to trauma, or severe drug reactions. When these conditions occur, most patients will respond to either volume expansion or vasopressor treatment. However, some patients will require excessive doses of vasopressors and will be deemed to be resistant.
Angiotensin II is a peptide hormone naturally produced by the body that regulates blood pressure via vasoconstriction and sodium reabsorption. LJPC-501 (angiotensin II) is being developed for the treatment of patients with catecholamine-resistant hypotension (CRH).
This is a multi-site, randomized, double-blind, placebo-controlled study. Adult patients with CRH, who are hospitalized in an ICU setting, may be eligible to participate. Approximately 315 patients will be enrolled.
Angiotensin II is a peptide hormone naturally produced by the body that regulates blood pressure via vasoconstriction and sodium reabsorption. LJPC-501 (angiotensin II) is being developed for the treatment of patients with catecholamine-resistant hypotension (CRH).
This is a multi-site, randomized, double-blind, placebo-controlled study. Adult patients with CRH, who are hospitalized in an ICU setting, may be eligible to participate. Approximately 315 patients will be enrolled.
Completion Date
Completion Date Type
Actual
Conditions
Catecholamine-resistant Hypotension (CRH)
Distributive Shock
High Output Shock
Sepsis
Eligibility Criteria
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.
1. Central venous oxygen saturation (ScvO2) \> 70% (either by oximetry catheter or by central venous blood gas) and central venous pressure (CVP) \> 8 mmHg.
OR
2. 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.
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.
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.
1. Central venous oxygen saturation (ScvO2) \> 70% (either by oximetry catheter or by central venous blood gas) and central venous pressure (CVP) \> 8 mmHg.
OR
2. 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.
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.
Inclusion Criteria
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.
1. Central venous oxygen saturation (ScvO2) \> 70% (either by oximetry catheter or by central venous blood gas) and central venous pressure (CVP) \> 8 mmHg.
OR
2. 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.
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.
1. Central venous oxygen saturation (ScvO2) \> 70% (either by oximetry catheter or by central venous blood gas) and central venous pressure (CVP) \> 8 mmHg.
OR
2. 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.
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT02338843
Org Class
Industry
Org Full Name
La Jolla Pharmaceutical Company
Org Study Id
LJ501-CRH01
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase 3, Placebo-Controlled, Randomized, Double-Blind, Multi-Center Study of LJPC-501 in Patients With Catecholamine-Resistant Hypotension (CRH)
Primary Outcomes
Outcome Description
Response with respect to mean arterial pressure (MAP) at hour 3 after the start of infusion was defined as an increase from baseline of at least 10 mm Hg or an increase to at least 75 mm Hg, without an increase in the dose of background vasopressors.
Outcome Measure
An Increased MAP, Defined as Achievement of a Day 1 MAP at 3 Hours Following the Initiation of Study Drug, of ≥ 75 mmHg OR a 10 mmHg Increase in Baseline MAP
Outcome Time Frame
Hour 3
Start Date
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Michelle Gong
Investigator Email
mgong@montefiore.org
Investigator Phone
718-920-5464
Categories Mesh Debug
COVID-19 --- INFECTIONS
Infectious Disease --- INFECTIONS
Diabetes & Endocrine System --- INFLAMMATION
MeSH Terms
SEPSIS
INFECTIONS
SYSTEMIC INFLAMMATORY RESPONSE SYNDROME
INFLAMMATION
PATHOLOGIC PROCESSES
PATHOLOGICAL CONDITIONS, SIGNS AND SYMPTOMS
ANGIOTENSIN I
ANGIOTENSIN II
COUNTERFEIT DRUGS
ANGIOTENSINS
PEPTIDE HORMONES
HORMONES
HORMONES, HORMONE SUBSTITUTES, AND HORMONE ANTAGONISTS
NEUROPEPTIDES
PEPTIDES
AMINO ACIDS, PEPTIDES, AND PROTEINS
OLIGOPEPTIDES
NERVE TISSUE PROTEINS
PROTEINS
AUTACOIDS
INFLAMMATION MEDIATORS
BIOLOGICAL FACTORS
SUBSTANDARD DRUGS
PHARMACEUTICAL PREPARATIONS