Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/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
Scientific title
A Phase 3, Placebo-Controlled, Randomized, Double-Blind, Multi-Center Study of LJPC-501 in Patients With Catecholamine-Resistant Hypotension (CRH)
Secondary ID [1] 0 0
LJ501-CRH01
Universal Trial Number (UTN)
Trial acronym
ATHOS-3
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Catecholamine-resistant Hypotension (CRH) 0 0
Distributive Shock 0 0
High Output Shock 0 0
Sepsis 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system
Cardiovascular 0 0 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
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
PBO
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
Hour 3

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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
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
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/03/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
18/02/2017
Sample size
Target
Accrual to date
Final
344
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,TAS,VIC,WA
Recruitment hospital [1] 0 0
Canberra Hospital - Garran
Recruitment hospital [2] 0 0
John Hunter Hospital - New Lambton Heights
Recruitment hospital [3] 0 0
Nepean Hospital - Penrith
Recruitment hospital [4] 0 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [5] 0 0
The Wesley Hospital - Auchenflower
Recruitment hospital [6] 0 0
Royal Brisbane & Women's Hospital - Herston
Recruitment hospital [7] 0 0
Gold Coast University Hospital - Southport
Recruitment hospital [8] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [9] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [10] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [11] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [12] 0 0
Frankston Hospital - Frankston
Recruitment hospital [13] 0 0
Austin Hospital - Heidelberg
Recruitment hospital [14] 0 0
St. Vincent's Hospital - Melbourne
Recruitment hospital [15] 0 0
Royal Melbourne Hospital - Parkville
Recruitment hospital [16] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [17] 0 0
Royal Perth Hospital - Perth
Recruitment hospital [18] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 0 0
2605 - Garran
Recruitment postcode(s) [2] 0 0
2305 - New Lambton Heights
Recruitment postcode(s) [3] 0 0
2751 - Penrith
Recruitment postcode(s) [4] 0 0
2065 - St Leonards
Recruitment postcode(s) [5] 0 0
4066 - Auchenflower
Recruitment postcode(s) [6] 0 0
4029 - Herston
Recruitment postcode(s) [7] 0 0
4215 - Southport
Recruitment postcode(s) [8] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [9] 0 0
5042 - Bedford Park
Recruitment postcode(s) [10] 0 0
7000 - Hobart
Recruitment postcode(s) [11] 0 0
3168 - Clayton
Recruitment postcode(s) [12] 0 0
3199 - Frankston
Recruitment postcode(s) [13] 0 0
3084 - Heidelberg
Recruitment postcode(s) [14] 0 0
3065 - Melbourne
Recruitment postcode(s) [15] 0 0
3050 - Parkville
Recruitment postcode(s) [16] 0 0
6150 - Murdoch
Recruitment postcode(s) [17] 0 0
6000 - Perth
Recruitment postcode(s) [18] 0 0
5000 - Adelaide
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Idaho
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Indiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Kentucky
Country [10] 0 0
United States of America
State/province [10] 0 0
Maryland
Country [11] 0 0
United States of America
State/province [11] 0 0
Massachusetts
Country [12] 0 0
United States of America
State/province [12] 0 0
Michigan
Country [13] 0 0
United States of America
State/province [13] 0 0
Minnesota
Country [14] 0 0
United States of America
State/province [14] 0 0
Missouri
Country [15] 0 0
United States of America
State/province [15] 0 0
Nevada
Country [16] 0 0
United States of America
State/province [16] 0 0
New Jersey
Country [17] 0 0
United States of America
State/province [17] 0 0
New York
Country [18] 0 0
United States of America
State/province [18] 0 0
North Carolina
Country [19] 0 0
United States of America
State/province [19] 0 0
Ohio
Country [20] 0 0
United States of America
State/province [20] 0 0
Oklahoma
Country [21] 0 0
United States of America
State/province [21] 0 0
Oregon
Country [22] 0 0
United States of America
State/province [22] 0 0
Pennsylvania
Country [23] 0 0
United States of America
State/province [23] 0 0
Tennessee
Country [24] 0 0
United States of America
State/province [24] 0 0
Texas
Country [25] 0 0
United States of America
State/province [25] 0 0
Virginia
Country [26] 0 0
Belgium
State/province [26] 0 0
Antwerp
Country [27] 0 0
Belgium
State/province [27] 0 0
Brussels
Country [28] 0 0
Belgium
State/province [28] 0 0
Brussel
Country [29] 0 0
Belgium
State/province [29] 0 0
Bruxelles
Country [30] 0 0
Belgium
State/province [30] 0 0
Gent
Country [31] 0 0
Canada
State/province [31] 0 0
Alberta
Country [32] 0 0
Canada
State/province [32] 0 0
British Columbia
Country [33] 0 0
Canada
State/province [33] 0 0
Ontario
Country [34] 0 0
Finland
State/province [34] 0 0
Helsinki
Country [35] 0 0
Finland
State/province [35] 0 0
Kuopio
Country [36] 0 0
Finland
State/province [36] 0 0
Tampere
Country [37] 0 0
Finland
State/province [37] 0 0
Turku
Country [38] 0 0
France
State/province [38] 0 0
Besancon
Country [39] 0 0
France
State/province [39] 0 0
Lille Cedex
Country [40] 0 0
France
State/province [40] 0 0
Nice
Country [41] 0 0
France
State/province [41] 0 0
Pessac
Country [42] 0 0
Germany
State/province [42] 0 0
Berlin
Country [43] 0 0
Germany
State/province [43] 0 0
Münster
Country [44] 0 0
New Zealand
State/province [44] 0 0
Auckland
Country [45] 0 0
New Zealand
State/province [45] 0 0
Wellington
Country [46] 0 0
Switzerland
State/province [46] 0 0
Bern
Country [47] 0 0
United Kingdom
State/province [47] 0 0
Hampshire
Country [48] 0 0
United Kingdom
State/province [48] 0 0
Norfolk
Country [49] 0 0
United Kingdom
State/province [49] 0 0
Tyne And Wear
Country [50] 0 0
United Kingdom
State/province [50] 0 0
West Midlands
Country [51] 0 0
United Kingdom
State/province [51] 0 0
Birmingham, West Midlands
Country [52] 0 0
United Kingdom
State/province [52] 0 0
Bristol
Country [53] 0 0
United Kingdom
State/province [53] 0 0
Cambridge
Country [54] 0 0
United Kingdom
State/province [54] 0 0
Hull
Country [55] 0 0
United Kingdom
State/province [55] 0 0
London
Country [56] 0 0
United Kingdom
State/province [56] 0 0
Merseyside
Country [57] 0 0
United Kingdom
State/province [57] 0 0
Northampton
Country [58] 0 0
United Kingdom
State/province [58] 0 0
Plymouth

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
La Jolla Pharmaceutical Company
Address
Country

Ethics approval
Ethics application status

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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02338843
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
George F Tidmarsh, MD, PhD
Address 0 0
La Jolla Pharmaceutical Company
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02338843