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

Sepsis Clinical Trial

— ATHOS-3  

Official title:

A Phase 3, Placebo-Controlled, Randomized, Double-Blind, Multi-Center Study of LJPC-501 in Patients With Catecholamine-Resistant Hypotension (CRH)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02338843
• Other study ID #: LJ501-CRH01
• Status: Completed
• Phase: Phase 3
• First received: January 1, 2015
• Last updated: February 27, 2018
• Start date: March 2015
• Est. completion date: February 18, 2017

Study information

• Verified date: January 2018
• Source: La Jolla Pharmaceutical Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 344
• Est. completion date: February 18, 2017
• Est. primary completion date: December 1, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• LJPC-501
Treatment arm
• Placebo
PBO

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide
Australia	The Wesley Hospital	Auchenflower	Queensland
Australia	Flinders Medical Centre	Bedford Park	South Australia
Australia	Monash Medical Centre	Clayton	Victoria
Australia	Frankston Hospital	Frankston	Victoria
Australia	Canberra Hospital	Garran	Australian Capital Territory
Australia	Austin Hospital	Heidelberg	Victoria
Australia	Royal Brisbane & Women's Hospital	Herston	Queensland
Australia	Royal Hobart Hospital	Hobart	Tasmania
Australia	St. Vincent's Hospital	Melbourne	Victoria
Australia	Fiona Stanley Hospital	Murdoch	Western Australia
Australia	John Hunter Hospital	New Lambton Heights	New South Wales
Australia	Royal Melbourne Hospital	Parkville	Victoria
Australia	Nepean Hospital	Penrith	New South Wales
Australia	Royal Perth Hospital	Perth	Western Australia
Australia	Gold Coast University Hospital	Southport	Queensland
Australia	Royal North Shore Hospital	St Leonards	New South Wales
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Belgium	UZ Antwerpen	Antwerp
Belgium	UZ Brussel	Brussel
Belgium	Brugmann University Hospital	Brussels
Belgium	Erasme University Hospital	Bruxelles
Belgium	UZ Gent	Gent
Canada	South Health Campus & Rockyview General Hospital	Calgary	Alberta
Canada	Royal Alexandra Hospital	Edmonton	Alberta
Canada	University of Alberta Hospital	Edmonton	Alberta
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	St. Paul's Hospital	Vancouver	British Columbia
Canada	Royal Jubilee Hospital	Victoria	British Columbia
Canada	Victoria General Hospital	Victoria	British Columbia
Finland	Helsinki University Central Hospital	Helsinki
Finland	Kuopio University Hospital	Kuopio
Finland	Tampere University Hospital	Tampere
Finland	Turku University Hospital	Turku
France	Jean Minjoz Hospital	Besancon
France	Hospital Roger Salengro, CHRU de Lille	Lille Cedex
France	CHU Nice	Nice
France	Bordeaux Hospital University Center	Pessac
Germany	University Medical Center, Berlin	Berlin
Germany	University Hospital Münster	Münster
New Zealand	Auckland City Hospital	Grafton	Auckland
New Zealand	Wellington Hospital	Newtown	Wellington
New Zealand	Middlemore Hospital	Otahuhu	Auckland
Switzerland	Bern University Hospital	Bern
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	Charing Cross Hospital	London
United Kingdom	Hammersmith Hospital	London
United Kingdom	Royal London Hospital	London
United Kingdom	St. George's University Hospital	London
United Kingdom	St. Thomas Hospital	London
United Kingdom	Royal Liverpool Hospital	Merseyside
United Kingdom	Northampton General Hospital	Northampton
United Kingdom	Norfolk and Norwich University Hospitals	Norwich	Norfolk
United Kingdom	Derriford Hospital	Plymouth
United Kingdom	Southampton General Hospital	Southampton	Hampshire
United Kingdom	Sunderland Royal Hospital	Sunderland	Tyne And Wear
United States	Lehigh Valley Health Network	Allentown	Pennsylvania
United States	Emory University	Atlanta	Georgia
United States	Joseph M. Still Research Foundation, Inc.	Augusta	Georgia
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	Montefiore Medical Center, Weiler Division	Bronx	New York
United States	Erlanger Hospital	Chattanooga	Tennessee
United States	Memorial Hospital	Chattanooga	Tennessee
United States	Northwestern University	Chicago	Illinois
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	Baylor University	Dallas	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Henry Ford Hospital	Detroit	Michigan
United States	Duke Regional Hospital	Durham	North Carolina
United States	Duke University Medical Center	Durham	North Carolina
United States	Englewood Hospital & Medical Center	Englewood	New Jersey
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	John Peter Smith Hospital - JPS Health Network	Fort Worth	Texas
United States	University of Florida	Gainesville	Florida
United States	Moses Cone Health	Greensboro	North Carolina
United States	Wesley Long Hospital	Greensboro	North Carolina
United States	Kentucky Lung Clinic	Hazard	Kentucky
United States	Eastern Idaho Regional Medical Center	Idaho Falls	Idaho
United States	Methodist Hospital, Indiana University Health Physicians	Indianapolis	Indiana
United States	Sunrise Hospital/eStudySite	Las Vegas	Nevada
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 Louisville	Louisville	Kentucky
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Pulmonary Associates of Mobile, PC	Mobile	Alabama
United States	Rutgers Robert Wood Johnson Medical Center	New Brunswick	New Jersey
United States	University of Oklahoma Medical Center	Oklahoma City	Oklahoma
United States	University of California, Irvine Medical Center	Orange	California
United States	Penn Presbyterian Medical Center	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Mayo Clinic Arizona	Phoenix	Arizona
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Oregon Health & Sciences University	Portland	Oregon
United States	Virginia Commonwealth University Medical Center	Richmond	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	University of California, Davis	Sacramento	California
United States	Saint Louis University	Saint Louis	Missouri
United States	St. Paul Regions Hospital	Saint Paul	Minnesota
United States	U.S. Army Military Medical Center	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
La Jolla Pharmaceutical Company

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	Hour 3