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Catecholamine-resistant Hypotension (CRH)Phase 3ATHOS-3NCT02338843

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

A Phase 3 study testing LJPC-501 in people with Catecholamine-resistant Hypotension (CRH) and Distributive Shock, run by La Jolla Pharmaceutical Company at 115 sites in 10 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
LJPC-501
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
344 participants
Where
115 sitesin 10 countries
Study dates
Mar 2015to 18 Feb 2017
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 9Show fewer
  • 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.

Who cannot join

  • 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.
Show all 19Show fewer
  • 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.

Trial locations and contacts

115 sites in 10 countries.

115 sites in 10 countries

United States52 sites

  • Lehigh Valley Health Network

    Allentown, Pennsylvania, 18103

  • Emory University

    Atlanta, Georgia, 30322

  • Joseph M. Still Research Foundation, Inc.

    Augusta, Georgia, 30909

  • University of Maryland Medical Center

    Baltimore, Maryland, 21201

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • Erlanger Hospital

    Chattanooga, Tennessee, 37408

  • Memorial Hospital

    Chattanooga, Tennessee, 37408

  • Northwestern University

    Chicago, Illinois, 60611

  • University of Cincinnati Medical Center

    Cincinnati, Ohio, 45267

  • Cleveland Clinic - Fairview Hospital

    Cleveland, Ohio, 44195

  • The Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Riverside Methodist Hospital

    Columbus, Ohio, 43215

  • Baylor University

    Dallas, Texas, 75246

  • Geisinger Medical Center

    Danville, Pennsylvania, 17822

  • Henry Ford Hospital

    Detroit, Michigan, 48202

  • Duke Regional Hospital

    Durham, North Carolina, 27704

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Englewood Hospital & Medical Center

    Englewood, New Jersey, 07631

  • Inova Fairfax Hospital

    Falls Church, Virginia, 22042

  • John Peter Smith Hospital - JPS Health Network

    Fort Worth, Texas, 76104

  • University of Florida

    Gainesville, Florida, 32610

  • Moses Cone Health

    Greensboro, North Carolina, 27403

  • Wesley Long Hospital

    Greensboro, North Carolina, 27403

  • Kentucky Lung Clinic

    Hazard, Kentucky, 41701

  • Eastern Idaho Regional Medical Center

    Idaho Falls, Idaho, 83404

  • Methodist Hospital, Indiana University Health Physicians

    Indianapolis, Indiana, 46202

  • Sunrise Hospital/eStudySite

    Las Vegas, Nevada, 89109

  • Loma Linda University Medical Center

    Loma Linda, California, 92354

  • Keck Hospital of USC

    Los Angeles, California, 90033

  • Los Angeles County + University of Southern California Medical Center

    Los Angeles, California, 90033

  • University of California, Los Angeles

    Los Angeles, California, 90095

  • University of Louisville

    Louisville, Kentucky, 40292

  • Hennepin County Medical Center

    Minneapolis, Minnesota, 55415

  • Pulmonary Associates of Mobile, PC

    Mobile, Alabama, 36608

  • Rutgers Robert Wood Johnson Medical Center

    New Brunswick, New Jersey, 08901

  • University of Oklahoma Medical Center

    Oklahoma City, Oklahoma, 73104

  • University of California, Irvine Medical Center

    Orange, California, 92868

  • Penn Presbyterian Medical Center

    Philadelphia, Pennsylvania, 19104

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Mayo Clinic Arizona

    Phoenix, Arizona, 85054

  • University of Pittsburgh Medical Center

    Pittsburgh, Pennsylvania, 15261

  • Oregon Health & Sciences University

    Portland, Oregon, 97239

  • Virginia Commonwealth University Medical Center

    Richmond, Virginia, 23298

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • University of California, Davis

    Sacramento, California, 95817

  • St. Paul Regions Hospital

    Saint Paul, Minnesota, 55101

  • U.S. Army Military Medical Center

    San Antonio, Texas, 78234

  • Saint Louis University

    St Louis, Missouri, 63104

  • Montefiore Medical Center, Weiler Division

    The Bronx, New York, 10461

  • Montefiore Medical Center

    The Bronx, New York, 10467

Other trials in United States

Australia18 sites

  • Royal Adelaide Hospital

    Adelaide, 5000

  • The Wesley Hospital

    Auchenflower, Queensland, 4066

  • Flinders Medical Centre

    Bedford Park, South Australia, 5042

  • Monash Medical Centre

    Clayton, Victoria, 3168

  • Frankston Hospital

    Frankston, Victoria, 3199

  • Canberra Hospital

    Garran, Australian Capital Territory, 2605

  • Austin Hospital

    Heidelberg, Victoria, 3084

  • Royal Brisbane & Women's Hospital

    Herston, Queensland, 4029

  • Royal Hobart Hospital

    Hobart, Tasmania, 7000

  • St. Vincent's Hospital

    Melbourne, Victoria, 3065

  • Fiona Stanley Hospital

    Murdoch, Western Australia, 6150

  • John Hunter Hospital

    New Lambton Heights, New South Wales, 2305

  • Royal Melbourne Hospital

    Parkville, Victoria, 3050

  • Nepean Hospital

    Penrith, New South Wales, 2751

  • Royal Perth Hospital

    Perth, Western Australia, 6000

  • Gold Coast University Hospital

    Southport, Queensland, 4215

  • Royal North Shore Hospital

    St Leonards, New South Wales, 2065

  • Princess Alexandra Hospital

    Woolloongabba, Queensland, 4102

Other trials in Australia

United Kingdom16 sites

  • Birmingham Heartlands Hospital

    Birmingham, West Midlands, B9 5SS

  • Queen Elizabeth Hospital

    Birmingham, West Midlands, B15 2WB

  • Bristol Royal Infirmary

    Bristol, BS2 8HW

  • Addenbrooke's Hospital

    Cambridge, CB2 0QQ

  • Hull Royal Infirmary

    Hull, HU3 2JZ

  • Royal London Hospital

    London, E1 1BB

  • St. Thomas Hospital

    London, SE1 7EH

  • St. George's University Hospital

    London, SW17 0QT

  • Charing Cross Hospital

    London, W6 8RF

  • Hammersmith Hospital

    London, W6 8RF

  • Royal Liverpool Hospital

    Merseyside, L7 8XP

  • Northampton General Hospital

    Northampton, NN1 5BD

  • Norfolk and Norwich University Hospitals

    Norwich, Norfolk, NR4 7UY

  • Derriford Hospital

    Plymouth, PL6 8DH

  • Southampton General Hospital

    Southampton, Hampshire, SO16 6YD

  • Sunderland Royal Hospital

    Sunderland, Tyne and Wear, SR4 7TP

Other trials in United Kingdom

Canada10 sites

  • South Health Campus & Rockyview General Hospital

    Calgary, Alberta, T2N 2T9

  • Royal Alexandra Hospital

    Edmonton, Alberta, T5H 3V9

  • University of Alberta Hospital

    Edmonton, Alberta, T6G 2B7

  • Kingston General Hospital

    Kingston, Ontario, K7I 2V7

  • The Ottawa Hospital - Civic Campus

    Ottawa, Ontario, KIH 8L6

  • The Ottawa Hospital - General Campus

    Ottawa, Ontario, KIH 8L6

  • St. Michael's Hospital

    Toronto, Ontario, M5B1W8

  • St. Paul's Hospital

    Vancouver, British Columbia, V6Z 1Y6

  • Royal Jubilee Hospital

    Victoria, British Columbia, V8R 1J8

  • Victoria General Hospital

    Victoria, British Columbia, V8Z 6R5

Other trials in Canada

Belgium5 sites

  • UZ Antwerpen

    Antwerp, 2650

  • Brugmann University Hospital

    Brussels, 1020

  • Erasme University Hospital

    Brussels, 1070

  • UZ Brussel

    Brussels, 1090

  • UZ Gent

    Ghent, 9000

Other trials in Belgium

Finland4 sites

  • Helsinki University Central Hospital

    Helsinki, 00290

  • Kuopio University Hospital

    Kuopio, 70210

  • Tampere University Hospital

    Tampere, 33520

  • Turku University Hospital

    Turku, 20521

Other trials in Finland

France4 sites

  • Jean Minjoz Hospital

    Besançon, 25030

  • Hospital Roger Salengro, CHRU de Lille

    Lille, 59037

  • CHU Nice

    Nice, 06202

  • Bordeaux Hospital University Center

    Pessac, 33604

Other trials in France

New Zealand3 sites

  • Auckland City Hospital

    Grafton, Auckland, 1023

  • Wellington Hospital

    Newtown, Wellington Region, 6021

  • Middlemore Hospital

    Otahuhu, Auckland

Other trials in New Zealand

Germany2 sites

  • University Medical Center, Berlin

    Berlin, 10117

  • University Hospital Münster

    Münster, 48149

Other trials in Germany

Switzerland1 site

  • Bern University Hospital

    Bern, CH-3010

Other trials in Switzerland

About this study

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

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.

Read the 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.

Being tested
LJPC-501, Placebo
Medical subject headings
Sepsis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LJPC-501Drug

    Also called angiotensin II

    Treatment arm

  • PlaceboDrug

    Also called 0.9% Sodium Chloride Solution USP

    PBO

Study groups in NCT02338843
Study groupRoleWhat they receive
LJPC-501 (angiotensin II)ExperimentalTreatment arm
Receives: Drug: LJPC-501
Placebo (0.9% sodium chloride solution)Placebo comparatorPlacebo arm
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Hour 3

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Jan 2015 (estimated)
  2. Study startMar 2015
  3. Primary completion1 Dec 2016
  4. Study completion18 Feb 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
344 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02338843
Sponsor's protocol ID
LJ501-CRH01
Acronym
ATHOS-3
Status last verified
Jan 2018
First submitted
1 Jan 2015
Last updated
27 Mar 2018
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 39972379

  • Leisman 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.

    PubMed 38637829

  • Leisman 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.

    PubMed 38103056

  • Wieruszewski 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.

    PubMed 37147690

  • Bellomo 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.

    PubMed 32609011

  • Bellomo 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.

    PubMed 32028998

  • Senatore 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.

    PubMed 30144016

  • Khanna 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.

    PubMed 28528561

  • Schmull 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.

    PubMed 26931475

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing LJPC-501 in people with Catecholamine-resistant Hypotension (CRH) and Distributive Shock, run by La Jolla Pharmaceutical Company at 115 sites in 10 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 115 sites in United States, Australia, United Kingdom, Canada, Belgium and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Jan 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary 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 (time frame: Hour 3). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02338843, which also lists 9 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2018.

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