A Phase 3 Study of LJPC-501 in Patients With Catecholamine-Resistant Hypotension
- Conditions
- Distributive ShockHigh Output ShockSepsisCatecholamine-resistant Hypotension (CRH)
- Interventions
- Drug: Placebo
- Registration Number
- NCT02338843
- Lead Sponsor
- La Jolla Pharmaceutical Company
- 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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 344
-
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.
-
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.
-
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.
-
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.
-
Patients must have clinical features of high-output shock by meeting one of the following criteria.
-
Central venous oxygen saturation (ScvO2) > 70% (either by oximetry catheter or by central venous blood gas) and central venous pressure (CVP) > 8 mmHg.
OR
-
Cardiac Index (CI) > 2.3 L/min/1.73 m2. Patient must meet 5a or 5b to be eligible.
-
-
Patient or legal surrogate is willing and able to provide written informed consent and comply with all protocol requirements.
- Patients who are < 18 years of age.
- Any patient with burns covering > 20% of total body surface area (TBSA).
- Patients with a Cardiovascular (CV) SOFA score ≤ 3.
- Patients diagnosed with acute occlusive coronary syndrome requiring intervention.
- Patients on veno-arterial (VA) ECMO.
- Patients who have been on ECMO for less than 12 hours.
- Patients in liver failure with a Model for End-Stage Liver Disease (MELD) score of ≥ 30.
- Patients with a history of asthma or who are currently experiencing bronchospasm requiring the use of inhaled bronchodilators, if not mechanically ventilated.
- Patients with acute mesenteric ischemia or a history of mesenteric ischemic.
- Patients with a history of, presence of, or highly-suspected of having an aortic dissection or abdominal aortic aneurysm.
- Patients requiring more than 500 mg daily of hydrocortisone or equivalent glucocorticoid medication as a standing dose.
- Patients with Raynaud's phenomenon, systemic sclerosis or vasospastic disease.
- Patients with an expected lifespan of < 12 hours.
- 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.
- Patients with active bleeding AND hemoglobin < 7g/dL or any other condition that would contraindicate serial blood sampling.
- Patients with an absolute neutrophil count (ANC) of < 1000 cells/mm3.
- Patients with a known allergy to mannitol.
- Patients who are current participating in another interventional clinical trial.
- Patients who are known to be pregnant at the time of Screening.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description LJPC-501 (angiotensin II) LJPC-501 Treatment arm Placebo (0.9% sodium chloride solution) Placebo Placebo arm
- Primary Outcome Measures
Name Time Method 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 Hour 3 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.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (115)
Joseph M. Still Research Foundation, Inc.
🇺🇸Augusta, Georgia, United States
Eastern Idaho Regional Medical Center
🇺🇸Idaho Falls, Idaho, United States
Pulmonary Associates of Mobile, PC
🇺🇸Mobile, Alabama, United States
Loma Linda University Medical Center
🇺🇸Loma Linda, California, United States
Memorial Hospital
🇺🇸Chattanooga, Tennessee, United States
University of Maryland Medical Center
🇺🇸Baltimore, Maryland, United States
Penn Presbyterian Medical Center
🇺🇸Philadelphia, Pennsylvania, United States
University of California, Los Angeles
🇺🇸Los Angeles, California, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Methodist Hospital, Indiana University Health Physicians
🇺🇸Indianapolis, Indiana, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Cleveland Clinic - Fairview Hospital
🇺🇸Cleveland, Ohio, United States
The Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
University of Florida
🇺🇸Gainesville, Florida, United States
UZ Antwerpen
🇧🇪Antwerp, Belgium
Emory University
🇺🇸Atlanta, Georgia, United States
UZ Gent
🇧🇪Gent, Belgium
University Hospital Münster
🇩🇪Münster, Germany
Brugmann University Hospital
🇧🇪Brussels, Belgium
Erasme University Hospital
🇧🇪Bruxelles, Belgium
Royal Jubilee Hospital
🇨🇦Victoria, British Columbia, Canada
Helsinki University Central Hospital
🇫🇮Helsinki, Finland
UZ Brussel
🇧🇪Brussel, Belgium
Bordeaux Hospital University Center
🇫🇷Pessac, France
South Health Campus & Rockyview General Hospital
🇨🇦Calgary, Alberta, Canada
Wellington Hospital
🇳🇿Newtown, Wellington, New Zealand
St. Paul's Hospital
🇨🇦Vancouver, British Columbia, Canada
Hospital Roger Salengro, CHRU de Lille
🇫🇷Lille Cedex, France
CHU Nice
🇫🇷Nice, France
Jean Minjoz Hospital
🇫🇷Besancon, France
Kuopio University Hospital
🇫🇮Kuopio, Finland
Auckland City Hospital
🇳🇿Grafton, Auckland, New Zealand
University Medical Center, Berlin
🇩🇪Berlin, Germany
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Hennepin County Medical Center
🇺🇸Minneapolis, Minnesota, United States
Sunrise Hospital/eStudySite
🇺🇸Las Vegas, Nevada, United States
Duke Regional Hospital
🇺🇸Durham, North Carolina, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
University of Oklahoma Medical Center
🇺🇸Oklahoma City, Oklahoma, United States
University of Cincinnati Medical Center
🇺🇸Cincinnati, Ohio, United States
U.S. Army Military Medical Center
🇺🇸San Antonio, Texas, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Oregon Health & Sciences University
🇺🇸Portland, Oregon, United States
Kingston General Hospital
🇨🇦Kingston, Ontario, Canada
University of Alberta Hospital
🇨🇦Edmonton, Alberta, Canada
The Ottawa Hospital - Civic Campus
🇨🇦Ottawa, Ontario, Canada
The Ottawa Hospital - General Campus
🇨🇦Ottawa, Ontario, Canada
Bristol Royal Infirmary
🇬🇧Bristol, United Kingdom
Hull Royal Infirmary
🇬🇧Hull, United Kingdom
Royal London Hospital
🇬🇧London, United Kingdom
St. George's University Hospital
🇬🇧London, United Kingdom
Northampton General Hospital
🇬🇧Northampton, United Kingdom
Royal Liverpool Hospital
🇬🇧Merseyside, United Kingdom
Flinders Medical Centre
🇦🇺Bedford Park, South Australia, Australia
Lehigh Valley Health Network
🇺🇸Allentown, Pennsylvania, United States
Mayo Clinic Arizona
🇺🇸Phoenix, Arizona, United States
Keck Hospital of USC
🇺🇸Los Angeles, California, United States
University of California, Irvine Medical Center
🇺🇸Orange, California, United States
Los Angeles County + University of Southern California Medical Center
🇺🇸Los Angeles, California, United States
University of California, Davis
🇺🇸Sacramento, California, United States
Kentucky Lung Clinic
🇺🇸Hazard, Kentucky, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
St. Paul Regions Hospital
🇺🇸Saint Paul, Minnesota, United States
Saint Louis University
🇺🇸Saint Louis, Missouri, United States
Englewood Hospital & Medical Center
🇺🇸Englewood, New Jersey, United States
Rutgers Robert Wood Johnson Medical Center
🇺🇸New Brunswick, New Jersey, United States
Montefiore Medical Center, Weiler Division
🇺🇸Bronx, New York, United States
Moses Cone Health
🇺🇸Greensboro, North Carolina, United States
Wesley Long Hospital
🇺🇸Greensboro, North Carolina, United States
Geisinger Medical Center
🇺🇸Danville, Pennsylvania, United States
Riverside Methodist Hospital
🇺🇸Columbus, Ohio, United States
Erlanger Hospital
🇺🇸Chattanooga, Tennessee, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
Baylor University
🇺🇸Dallas, Texas, United States
John Peter Smith Hospital - JPS Health Network
🇺🇸Fort Worth, Texas, United States
Virginia Commonwealth University Medical Center
🇺🇸Richmond, Virginia, United States
Inova Fairfax Hospital
🇺🇸Falls Church, Virginia, United States
Canberra Hospital
🇦🇺Garran, Australian Capital Territory, Australia
John Hunter Hospital
🇦🇺New Lambton Heights, New South Wales, Australia
Royal North Shore Hospital
🇦🇺St Leonards, New South Wales, Australia
Nepean Hospital
🇦🇺Penrith, New South Wales, Australia
The Wesley Hospital
🇦🇺Auchenflower, Queensland, Australia
Royal Brisbane & Women's Hospital
🇦🇺Herston, Queensland, Australia
Princess Alexandra Hospital
🇦🇺Woolloongabba, Queensland, Australia
Gold Coast University Hospital
🇦🇺Southport, Queensland, Australia
Monash Medical Centre
🇦🇺Clayton, Victoria, Australia
Royal Hobart Hospital
🇦🇺Hobart, Tasmania, Australia
Frankston Hospital
🇦🇺Frankston, Victoria, Australia
Austin Hospital
🇦🇺Heidelberg, Victoria, Australia
Royal Melbourne Hospital
🇦🇺Parkville, Victoria, Australia
St. Vincent's Hospital
🇦🇺Melbourne, Victoria, Australia
Royal Perth Hospital
🇦🇺Perth, Western Australia, Australia
Fiona Stanley Hospital
🇦🇺Murdoch, Western Australia, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, Australia
Royal Alexandra Hospital
🇨🇦Edmonton, Alberta, Canada
St. Michael's Hospital
🇨🇦Toronto, Ontario, Canada
Middlemore Hospital
🇳🇿Otahuhu, Auckland, New Zealand
Sunderland Royal Hospital
🇬🇧Sunderland, Tyne And Wear, United Kingdom
Birmingham Heartlands Hospital
🇬🇧Birmingham, West Midlands, United Kingdom
Queen Elizabeth Hospital
🇬🇧Birmingham, West Midlands, United Kingdom
Addenbrooke's Hospital
🇬🇧Cambridge, United Kingdom
Hammersmith Hospital
🇬🇧London, United Kingdom
Derriford Hospital
🇬🇧Plymouth, United Kingdom
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
St. Thomas Hospital
🇬🇧London, United Kingdom
University of Louisville
🇺🇸Louisville, Kentucky, United States
Victoria General Hospital
🇨🇦Victoria, British Columbia, Canada
Southampton General Hospital
🇬🇧Southampton, Hampshire, United Kingdom
Bern University Hospital
🇨🇭Bern, Switzerland
Norfolk and Norwich University Hospitals
🇬🇧Norwich, Norfolk, United Kingdom
Turku University Hospital
🇫🇮Turku, Finland
Tampere University Hospital
🇫🇮Tampere, Finland
Montefiore Medical Center
🇺🇸Bronx, New York, United States
Charing Cross Hospital
🇬🇧London, United Kingdom