A Phase 3 Study of LJPC-501 in Patients With Catecholamine-Resistant Hypotension

NCT ID: NCT02338843

Last Updated: 2018-03-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 344 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-03-31
• Study Completion Date: 2017-02-18

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.

Conditions

Catecholamine-resistant Hypotension (CRH); Distributive Shock; High Output Shock; Sepsis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

LJPC-501 (angiotensin II)

Treatment arm

Group Type: EXPERIMENTAL

LJPC-501

Intervention Type: DRUG

Treatment arm

Placebo (0.9% sodium chloride solution)

Placebo arm

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

PBO

Interventions

LJPC-501

Treatment arm

Intervention Type: DRUG

Placebo

PBO

Intervention Type: DRUG

Other Intervention Names

angiotensin II; 0.9% Sodium Chloride Solution USP

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

La Jolla Pharmaceutical Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

George F Tidmarsh, MD, PhD

Role: STUDY_DIRECTOR

La Jolla Pharmaceutical Company

Locations

Pulmonary Associates of Mobile, PC

Mobile, Alabama, United States

Mayo Clinic Arizona

Phoenix, Arizona, United States

Loma Linda University Medical Center

Loma Linda, California, United States

Keck Hospital of USC

Los Angeles, California, United States

Los Angeles County + University of Southern California Medical Center

Los Angeles, California, United States

University of California, Los Angeles

Los Angeles, California, United States

University of California, Irvine Medical Center

Orange, California, United States

University of California, Davis

Sacramento, California, United States

University of Florida

Gainesville, Florida, United States

Emory University

Atlanta, Georgia, United States

Joseph M. Still Research Foundation, Inc.

Augusta, Georgia, United States

Eastern Idaho Regional Medical Center

Idaho Falls, Idaho, United States

Northwestern University

Chicago, Illinois, United States

Methodist Hospital, Indiana University Health Physicians

Indianapolis, Indiana, United States

Kentucky Lung Clinic

Hazard, Kentucky, United States

University of Louisville

Louisville, Kentucky, United States

University of Maryland Medical Center

Baltimore, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Henry Ford Hospital

Detroit, Michigan, United States

Hennepin County Medical Center

Minneapolis, Minnesota, United States

Mayo Clinic

Rochester, Minnesota, United States

St. Paul Regions Hospital

Saint Paul, Minnesota, United States

Saint Louis University

St Louis, Missouri, United States

Sunrise Hospital/eStudySite

Las Vegas, Nevada, 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

The Bronx, New York, United States

Montefiore Medical Center

The Bronx, New York, United States

Duke Regional Hospital

Durham, North Carolina, United States

Duke University Medical Center

Durham, North Carolina, United States

Moses Cone Health

Greensboro, North Carolina, United States

Wesley Long Hospital

Greensboro, North Carolina, United States

University of Cincinnati Medical Center

Cincinnati, Ohio, United States

Cleveland Clinic - Fairview Hospital

Cleveland, Ohio, United States

The Cleveland Clinic Foundation

Cleveland, Ohio, United States

Riverside Methodist Hospital

Columbus, Ohio, United States

University of Oklahoma Medical Center

Oklahoma City, Oklahoma, United States

Oregon Health & Sciences University

Portland, Oregon, United States

Lehigh Valley Health Network

Allentown, Pennsylvania, United States

Geisinger Medical Center

Danville, Pennsylvania, United States

Penn Presbyterian Medical Center

Philadelphia, Pennsylvania, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Erlanger Hospital

Chattanooga, Tennessee, United States

Memorial Hospital

Chattanooga, Tennessee, United States

Baylor University

Dallas, Texas, United States

John Peter Smith Hospital - JPS Health Network

Fort Worth, Texas, United States

U.S. Army Military Medical Center

San Antonio, Texas, United States

Inova Fairfax Hospital

Falls Church, Virginia, United States

Virginia Commonwealth University Medical Center

Richmond, Virginia, United States

Canberra Hospital

Garran, Australian Capital Territory, Australia

John Hunter Hospital

New Lambton Heights, New South Wales, Australia

Nepean Hospital

Penrith, New South Wales, Australia

Royal North Shore Hospital

St Leonards, New South Wales, Australia

The Wesley Hospital

Auchenflower, Queensland, Australia

Royal Brisbane & Women's Hospital

Herston, Queensland, Australia

Gold Coast University Hospital

Southport, Queensland, Australia

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Flinders Medical Centre

Bedford Park, South Australia, Australia

Royal Hobart Hospital

Hobart, Tasmania, Australia

Monash Medical Centre

Clayton, Victoria, Australia

Frankston Hospital

Frankston, Victoria, Australia

Austin Hospital

Heidelberg, Victoria, Australia

St. Vincent's Hospital

Melbourne, Victoria, Australia

Royal Melbourne Hospital

Parkville, Victoria, Australia

Fiona Stanley Hospital

Murdoch, Western Australia, Australia

Royal Perth Hospital

Perth, Western Australia, Australia

Royal Adelaide Hospital

Adelaide, , Australia

UZ Antwerpen

Antwerp, , Belgium

Brugmann University Hospital

Brussels, , Belgium

Erasme University Hospital

Brussels, , Belgium

UZ Brussel

Brussels, , Belgium

UZ Gent

Ghent, , Belgium

South Health Campus & Rockyview General Hospital

Calgary, Alberta, Canada

Royal Alexandra Hospital

Edmonton, Alberta, Canada

University of Alberta Hospital

Edmonton, Alberta, Canada

St. Paul's Hospital

Vancouver, British Columbia, Canada

Royal Jubilee Hospital

Victoria, British Columbia, Canada

Victoria General Hospital

Victoria, British Columbia, Canada

Kingston General Hospital

Kingston, Ontario, Canada

The Ottawa Hospital - Civic Campus

Ottawa, Ontario, Canada

The Ottawa Hospital - General Campus

Ottawa, Ontario, Canada

St. Michael's Hospital

Toronto, Ontario, Canada

Helsinki University Central Hospital

Helsinki, , Finland

Kuopio University Hospital

Kuopio, , Finland

Tampere University Hospital

Tampere, , Finland

Turku University Hospital

Turku, , Finland

Jean Minjoz Hospital

Besançon, , France

Hospital Roger Salengro, CHRU de Lille

Lille, , France

CHU Nice

Nice, , France

Bordeaux Hospital University Center

Pessac, , France

University Medical Center, Berlin

Berlin, , Germany

University Hospital Münster

Münster, , Germany

Auckland City Hospital

Grafton, Auckland, New Zealand

Middlemore Hospital

Otahuhu, Auckland, New Zealand

Wellington Hospital

Newtown, Wellington Region, New Zealand

Bern University Hospital

Bern, , Switzerland

Southampton General Hospital

Southampton, Hampshire, United Kingdom

Norfolk and Norwich University Hospitals

Norwich, Norfolk, United Kingdom

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

Bristol Royal Infirmary

Bristol, , United Kingdom

Addenbrooke's Hospital

Cambridge, , United Kingdom

Hull Royal Infirmary

Hull, , United Kingdom

Royal London Hospital

London, , United Kingdom

St. Thomas Hospital

London, , United Kingdom

St. George's University Hospital

London, , United Kingdom

Charing Cross Hospital

London, , United Kingdom

Hammersmith Hospital

London, , United Kingdom

Royal Liverpool Hospital

Merseyside, , United Kingdom

Northampton General Hospital

Northampton, , United Kingdom

Derriford Hospital

Plymouth, , United Kingdom

Countries

United States; Australia; Belgium; Canada; Finland; France; Germany; New Zealand; Switzerland; United Kingdom

References

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Other Identifiers

LJ501-CRH01

Identifier Type: -

Identifier Source: org_study_id