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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT02338843
Registration number
NCT02338843
Ethics application status
Date submitted
1/01/2015
Date registered
14/01/2015
Date last updated
27/03/2018
Titles & IDs
Public title
A Phase 3 Study of LJPC-501 in Patients With Catecholamine-Resistant Hypotension
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Scientific title
A Phase 3, Placebo-Controlled, Randomized, Double-Blind, Multi-Center Study of LJPC-501 in Patients With Catecholamine-Resistant Hypotension (CRH)
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Secondary ID [1]
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LJ501-CRH01
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Universal Trial Number (UTN)
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Trial acronym
ATHOS-3
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Catecholamine-resistant Hypotension (CRH)
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Distributive Shock
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High Output Shock
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Sepsis
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Condition category
Condition code
Cardiovascular
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Diseases of the vasculature and circulation including the lymphatic system
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Cardiovascular
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Other cardiovascular diseases
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - LJPC-501
Treatment: Drugs - Placebo
Experimental: LJPC-501 (angiotensin II) - Treatment arm
Placebo comparator: Placebo (0.9% sodium chloride solution) - Placebo arm
Treatment: Drugs: LJPC-501
Treatment arm
Treatment: Drugs: Placebo
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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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
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Assessment method [1]
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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.
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Timepoint [1]
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Hour 3
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Eligibility
Key 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.
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key 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.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
1/03/2015
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
18/02/2017
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Sample size
Target
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Accrual to date
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Final
344
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Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,TAS,VIC,WA
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Recruitment hospital [1]
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Canberra Hospital - Garran
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John Hunter Hospital - New Lambton Heights
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Nepean Hospital - Penrith
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Royal North Shore Hospital - St Leonards
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The Wesley Hospital - Auchenflower
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Royal Brisbane & Women's Hospital - Herston
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Gold Coast University Hospital - Southport
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Princess Alexandra Hospital - Woolloongabba
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Flinders Medical Centre - Bedford Park
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Monash Medical Centre - Clayton
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Frankston Hospital - Frankston
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Austin Hospital - Heidelberg
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St. Vincent's Hospital - Melbourne
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Royal Melbourne Hospital - Parkville
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Fiona Stanley Hospital - Murdoch
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Royal Perth Hospital - Perth
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Royal Adelaide Hospital - Adelaide
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2605 - Garran
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2305 - New Lambton Heights
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2751 - Penrith
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2065 - St Leonards
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4066 - Auchenflower
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4029 - Herston
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4215 - Southport
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4102 - Woolloongabba
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5042 - Bedford Park
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7000 - Hobart
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3168 - Clayton
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3199 - Frankston
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3084 - Heidelberg
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3065 - Melbourne
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3050 - Parkville
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6150 - Murdoch
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6000 - Perth
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5000 - Adelaide
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Recruitment outside Australia
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
La Jolla Pharmaceutical Company
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Address
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Ethics approval
Ethics application status
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Summary
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.
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Trial website
https://clinicaltrials.gov/study/NCT02338843
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Trial related presentations / publications
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. 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. 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. Erratum In: Am J Cardiovasc Drugs. 2019 Apr;19(2):227. doi: 10.1007/s40256-019-00335-7. 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. 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.
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Public notes
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Contacts
Principal investigator
Name
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George F Tidmarsh, MD, PhD
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Address
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La Jolla Pharmaceutical Company
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Contact person for scientific queries
No information has been provided regarding IPD availability
What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results are available at
https://clinicaltrials.gov/study/NCT02338843
Download to PDF