Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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 evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02338843
Recruitment Status : Completed
First Posted : January 14, 2015
Results First Posted : January 17, 2018
Last Update Posted : March 27, 2018
Sponsor:
Information provided by (Responsible Party):
La Jolla Pharmaceutical Company

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.

Condition or disease Intervention/treatment Phase
Catecholamine-resistant Hypotension (CRH) Distributive Shock High Output Shock Sepsis Drug: LJPC-501 Drug: Placebo Phase 3

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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 344 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Placebo-Controlled, Randomized, Double-Blind, Multi-Center Study of LJPC-501 in Patients With Catecholamine-Resistant Hypotension (CRH)
Study Start Date : March 2015
Actual Primary Completion Date : December 1, 2016
Actual Study Completion Date : February 18, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: LJPC-501 (angiotensin II)
Treatment arm
Drug: LJPC-501
Treatment arm
Other Name: angiotensin II

Placebo Comparator: Placebo (0.9% sodium chloride solution)
Placebo arm
Drug: Placebo
PBO
Other Name: 0.9% Sodium Chloride Solution USP




Primary Outcome Measures :
  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 [ Time Frame: Hour 3 ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02338843


  Show 115 Study Locations
Sponsors and Collaborators
La Jolla Pharmaceutical Company
Investigators
Layout table for investigator information
Study Director: George F Tidmarsh, MD, PhD La Jolla Pharmaceutical Company

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: La Jolla Pharmaceutical Company
ClinicalTrials.gov Identifier: NCT02338843     History of Changes
Other Study ID Numbers: LJ501-CRH01
First Posted: January 14, 2015    Key Record Dates
Results First Posted: January 17, 2018
Last Update Posted: March 27, 2018
Last Verified: January 2018
Additional relevant MeSH terms:
Layout table for MeSH terms
Hypotension
Shock
Pathologic Processes
Vascular Diseases
Cardiovascular Diseases
Angiotensin II
Giapreza
Angiotensinogen
Vasoconstrictor Agents
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action