A Phase 3 Study of LJPC-501 in Patients With Catecholamine-Resistant Hypotension
ATHOS-3
A Phase 3, Placebo-Controlled, Randomized, Double-Blind, Multi-Center Study of LJPC-501 in Patients With Catecholamine-Resistant Hypotension (CRH)
1 other identifier
interventional
344
10 countries
115
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Mar 2015
115 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 1, 2015
CompletedFirst Posted
Study publicly available on registry
January 14, 2015
CompletedStudy Start
First participant enrolled
March 1, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
February 18, 2017
CompletedResults Posted
Study results publicly available
January 17, 2018
CompletedMarch 27, 2018
January 1, 2018
1.8 years
January 1, 2015
November 28, 2017
February 27, 2018
Conditions
Outcome Measures
Primary Outcomes (1)
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
Study Arms (2)
LJPC-501 (angiotensin II)
EXPERIMENTALTreatment arm
Placebo (0.9% sodium chloride solution)
PLACEBO COMPARATORPlacebo arm
Interventions
Eligibility Criteria
You may qualify if:
- 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.
- 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.
You may not qualify if:
- 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.
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (115)
Pulmonary Associates of Mobile, PC
Mobile, Alabama, 36608, United States
Mayo Clinic Arizona
Phoenix, Arizona, 85054, United States
Loma Linda University Medical Center
Loma Linda, California, 92354, United States
Keck Hospital of USC
Los Angeles, California, 90033, United States
Los Angeles County + University of Southern California Medical Center
Los Angeles, California, 90033, United States
University of California, Los Angeles
Los Angeles, California, 90095, United States
University of California, Irvine Medical Center
Orange, California, 92868, United States
University of California, Davis
Sacramento, California, 95817, United States
University of Florida
Gainesville, Florida, 32610, United States
Emory University
Atlanta, Georgia, 30322, United States
Joseph M. Still Research Foundation, Inc.
Augusta, Georgia, 30909, United States
Eastern Idaho Regional Medical Center
Idaho Falls, Idaho, 83404, United States
Northwestern University
Chicago, Illinois, 60611, United States
Methodist Hospital, Indiana University Health Physicians
Indianapolis, Indiana, 46202, United States
Kentucky Lung Clinic
Hazard, Kentucky, 41701, United States
University of Louisville
Louisville, Kentucky, 40292, United States
University of Maryland Medical Center
Baltimore, Maryland, 21201, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Brigham and Women's Hospital
Boston, Massachusetts, 02115, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215, United States
Henry Ford Hospital
Detroit, Michigan, 48202, United States
Hennepin County Medical Center
Minneapolis, Minnesota, 55415, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
St. Paul Regions Hospital
Saint Paul, Minnesota, 55101, United States
Saint Louis University
St Louis, Missouri, 63104, United States
Sunrise Hospital/eStudySite
Las Vegas, Nevada, 89109, United States
Englewood Hospital & Medical Center
Englewood, New Jersey, 07631, United States
Rutgers Robert Wood Johnson Medical Center
New Brunswick, New Jersey, 08901, United States
Montefiore Medical Center, Weiler Division
The Bronx, New York, 10461, United States
Montefiore Medical Center
The Bronx, New York, 10467, United States
Duke Regional Hospital
Durham, North Carolina, 27704, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
Moses Cone Health
Greensboro, North Carolina, 27403, United States
Wesley Long Hospital
Greensboro, North Carolina, 27403, United States
University of Cincinnati Medical Center
Cincinnati, Ohio, 45267, United States
Cleveland Clinic - Fairview Hospital
Cleveland, Ohio, 44195, United States
The Cleveland Clinic Foundation
Cleveland, Ohio, 44195, United States
Riverside Methodist Hospital
Columbus, Ohio, 43215, United States
University of Oklahoma Medical Center
Oklahoma City, Oklahoma, 73104, United States
Oregon Health & Sciences University
Portland, Oregon, 97239, United States
Lehigh Valley Health Network
Allentown, Pennsylvania, 18103, United States
Geisinger Medical Center
Danville, Pennsylvania, 17822, United States
Penn Presbyterian Medical Center
Philadelphia, Pennsylvania, 19104, United States
University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15261, United States
Erlanger Hospital
Chattanooga, Tennessee, 37408, United States
Memorial Hospital
Chattanooga, Tennessee, 37408, United States
Baylor University
Dallas, Texas, 75246, United States
John Peter Smith Hospital - JPS Health Network
Fort Worth, Texas, 76104, United States
U.S. Army Military Medical Center
San Antonio, Texas, 78234, United States
Inova Fairfax Hospital
Falls Church, Virginia, 22042, United States
Virginia Commonwealth University Medical Center
Richmond, Virginia, 23298, United States
Canberra Hospital
Garran, Australian Capital Territory, 2605, Australia
John Hunter Hospital
New Lambton Heights, New South Wales, 2305, Australia
Nepean Hospital
Penrith, New South Wales, 2751, Australia
Royal North Shore Hospital
St Leonards, New South Wales, 2065, Australia
The Wesley Hospital
Auchenflower, Queensland, 4066, Australia
Royal Brisbane & Women's Hospital
Herston, Queensland, 4029, Australia
Gold Coast University Hospital
Southport, Queensland, 4215, Australia
Princess Alexandra Hospital
Woolloongabba, Queensland, 4102, Australia
Flinders Medical Centre
Bedford Park, South Australia, 5042, Australia
Royal Hobart Hospital
Hobart, Tasmania, 7000, Australia
Monash Medical Centre
Clayton, Victoria, 3168, Australia
Frankston Hospital
Frankston, Victoria, 3199, Australia
Austin Hospital
Heidelberg, Victoria, 3084, Australia
St. Vincent's Hospital
Melbourne, Victoria, 3065, Australia
Royal Melbourne Hospital
Parkville, Victoria, 3050, Australia
Fiona Stanley Hospital
Murdoch, Western Australia, 6150, Australia
Royal Perth Hospital
Perth, Western Australia, 6000, Australia
Royal Adelaide Hospital
Adelaide, 5000, Australia
UZ Antwerpen
Antwerp, 2650, Belgium
Brugmann University Hospital
Brussels, 1020, Belgium
Erasme University Hospital
Brussels, 1070, Belgium
UZ Brussel
Brussels, 1090, Belgium
UZ Gent
Ghent, 9000, Belgium
South Health Campus & Rockyview General Hospital
Calgary, Alberta, T2N 2T9, Canada
Royal Alexandra Hospital
Edmonton, Alberta, T5H 3V9, Canada
University of Alberta Hospital
Edmonton, Alberta, T6G 2B7, Canada
St. Paul's Hospital
Vancouver, British Columbia, V6Z 1Y6, Canada
Royal Jubilee Hospital
Victoria, British Columbia, V8R 1J8, Canada
Victoria General Hospital
Victoria, British Columbia, V8Z 6R5, Canada
Kingston General Hospital
Kingston, Ontario, K7I 2V7, Canada
The Ottawa Hospital - Civic Campus
Ottawa, Ontario, KIH 8L6, Canada
The Ottawa Hospital - General Campus
Ottawa, Ontario, KIH 8L6, Canada
St. Michael's Hospital
Toronto, Ontario, M5B1W8, Canada
Helsinki University Central Hospital
Helsinki, 00290, Finland
Kuopio University Hospital
Kuopio, 70210, Finland
Tampere University Hospital
Tampere, 33520, Finland
Turku University Hospital
Turku, 20521, Finland
Jean Minjoz Hospital
Besançon, 25030, France
Hospital Roger Salengro, CHRU de Lille
Lille, 59037, France
CHU Nice
Nice, 06202, France
Bordeaux Hospital University Center
Pessac, 33604, France
University Medical Center, Berlin
Berlin, 10117, Germany
University Hospital Münster
Münster, 48149, Germany
Auckland City Hospital
Grafton, Auckland, 1023, New Zealand
Middlemore Hospital
Otahuhu, Auckland, New Zealand
Wellington Hospital
Newtown, Wellington Region, 6021, New Zealand
Bern University Hospital
Bern, CH-3010, Switzerland
Southampton General Hospital
Southampton, Hampshire, SO16 6YD, United Kingdom
Norfolk and Norwich University Hospitals
Norwich, Norfolk, NR4 7UY, United Kingdom
Sunderland Royal Hospital
Sunderland, Tyne and Wear, SR4 7TP, United Kingdom
Birmingham Heartlands Hospital
Birmingham, West Midlands, B9 5SS, United Kingdom
Queen Elizabeth Hospital
Birmingham, West Midlands, B15 2WB, United Kingdom
Bristol Royal Infirmary
Bristol, BS2 8HW, United Kingdom
Addenbrooke's Hospital
Cambridge, CB2 0QQ, United Kingdom
Hull Royal Infirmary
Hull, HU3 2JZ, United Kingdom
Royal London Hospital
London, E1 1BB, United Kingdom
St. Thomas Hospital
London, SE1 7EH, United Kingdom
St. George's University Hospital
London, SW17 0QT, United Kingdom
Charing Cross Hospital
London, W6 8RF, United Kingdom
Hammersmith Hospital
London, W6 8RF, United Kingdom
Royal Liverpool Hospital
Merseyside, L7 8XP, United Kingdom
Northampton General Hospital
Northampton, NN1 5BD, United Kingdom
Derriford Hospital
Plymouth, PL6 8DH, United Kingdom
Related Publications (9)
Leisman DE, Wieruszewski PM, Busse LW, Chawla LS, Hibbert KA, Handisides DR, Khanna AK, Ostermann M, McCurdy MT, Adams CD, Hodges TN, Bellomo R; ATHOS-3 Investigators. An index of the initial blood pressure response to angiotensin II treatment and its association with clinical outcomes in vasodilatory shock. Crit Care. 2025 Feb 19;29(1):81. doi: 10.1186/s13054-025-05311-z.
PMID: 39972379DERIVEDLeisman DE, Handisides DR, Busse LW, Chappell MC, Chawla LS, Filbin MR, Goldberg MB, Ham KR, Khanna AK, Ostermann M, McCurdy MT, Adams CD, Hodges TN, Bellomo R; ATHOS-3 Investigators. ACE inhibitors and angiotensin receptor blockers differentially alter the response to angiotensin II treatment in vasodilatory shock. Crit Care. 2024 Apr 18;28(1):130. doi: 10.1186/s13054-024-04910-6.
PMID: 38637829DERIVEDLeisman DE, Handisides DR, Chawla LS, Albertson TE, Busse LW, Boldt DW, Deane AM, Gong MN, Ham KR, Khanna AK, Ostermann M, McCurdy MT, Thompson BT, Tumlin JS, Adams CD, Hodges TN, Bellomo R. Angiotensin II treatment is associated with improved oxygenation in ARDS patients with refractory vasodilatory shock. Ann Intensive Care. 2023 Dec 16;13(1):128. doi: 10.1186/s13613-023-01227-5.
PMID: 38103056DERIVEDWieruszewski PM, Bellomo R, Busse LW, Ham KR, Zarbock A, Khanna AK, Deane AM, Ostermann M, Wunderink RG, Boldt DW, Kroll S, Greenfeld CR, Hodges T, Chow JH; Angiotensin II for the Treatment of High-Output Shock 3 (ATHOS-3) Investigators. Initiating angiotensin II at lower vasopressor doses in vasodilatory shock: an exploratory post-hoc analysis of the ATHOS-3 clinical trial. Crit Care. 2023 May 5;27(1):175. doi: 10.1186/s13054-023-04446-1.
PMID: 37147690DERIVEDBellomo R, Forni LG, Busse LW, McCurdy MT, Ham KR, Boldt DW, Hastbacka J, Khanna AK, Albertson TE, Tumlin J, Storey K, Handisides D, Tidmarsh GF, Chawla LS, Ostermann M. Renin and Survival in Patients Given Angiotensin II for Catecholamine-Resistant Vasodilatory Shock. A Clinical Trial. Am J Respir Crit Care Med. 2020 Nov 1;202(9):1253-1261. doi: 10.1164/rccm.201911-2172OC.
PMID: 32609011DERIVEDBellomo R, Wunderink RG, Szerlip H, English SW, Busse LW, Deane AM, Khanna AK, McCurdy MT, Ostermann M, Young PJ, Handisides DR, Chawla LS, Tidmarsh GF, Albertson TE. Angiotensin I and angiotensin II concentrations and their ratio in catecholamine-resistant vasodilatory shock. Crit Care. 2020 Feb 6;24(1):43. doi: 10.1186/s13054-020-2733-x.
PMID: 32028998DERIVEDSenatore F, Jagadeesh G, Rose M, Pillai VC, Hariharan S, Liu Q, McDowell TY, Sapru MK, Southworth MR, Stockbridge N. FDA Approval of Angiotensin II for the Treatment of Hypotension in Adults with Distributive Shock. Am J Cardiovasc Drugs. 2019 Feb;19(1):11-20. doi: 10.1007/s40256-018-0297-9.
PMID: 30144016DERIVEDKhanna A, English SW, Wang XS, Ham K, Tumlin J, Szerlip H, Busse LW, Altaweel L, Albertson TE, Mackey C, McCurdy MT, Boldt DW, Chock S, Young PJ, Krell K, Wunderink RG, Ostermann M, Murugan R, Gong MN, Panwar R, Hastbacka J, Favory R, Venkatesh B, Thompson BT, Bellomo R, Jensen J, Kroll S, Chawla LS, Tidmarsh GF, Deane AM; ATHOS-3 Investigators. Angiotensin II for the Treatment of Vasodilatory Shock. N Engl J Med. 2017 Aug 3;377(5):419-430. doi: 10.1056/NEJMoa1704154. Epub 2017 May 21.
PMID: 28528561DERIVEDSchmull S, Wang Z, Gao L, Lv J, Li J, Xue S. Angiotensins and Their Receptors in Cardiac and Vascular Injury. Curr Hypertens Rev. 2016;12(3):170-180. doi: 10.2174/1573402112666160302101545.
PMID: 26931475DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- George Tidmarsh, MD, PhD
- Organization
- La Jolla Pharmaceutical Company
Study Officials
- STUDY DIRECTOR
George F Tidmarsh, MD, PhD
La Jolla Pharmaceutical Company
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 1, 2015
First Posted
January 14, 2015
Study Start
March 1, 2015
Primary Completion
December 1, 2016
Study Completion
February 18, 2017
Last Updated
March 27, 2018
Results First Posted
January 17, 2018
Record last verified: 2018-01