Intravenous AII for the Treatment of Severe Hypotension in High Output Shock: A Pilot Study

NCT ID: NCT01393782

Last Updated: 2024-04-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-07-31
• Study Completion Date: 2014-01-31

Brief Summary

The investigators propose a dose finding study to determine the feasibility of Angiotensin II (AII) to increase mean arterial pressure in high-output shock. If AII can be shown to increase mean arterial pressure, this could lead to future pharmacologic development based on the AII hormonal pathway. The investigators propose a 20 patient, randomized, placebo-controlled, blinded study in the treatment of high-output shock. Patients with high-output shock and a cardiovascular SOFA (sequential organ failure score) score of > 4 will be eligible. In addition, patients must already be receiving cardiac output monitoring and have a cardiac index > 2.4 L/min/ 1.73 m2. Patients will be randomized to intravenous AII or saline in a blinded fashion. There will be 10 patients in each arm. This is a safety and dose finding feasibility study. The investigators are starting with a small cohort consistent with similar types of studies. The investigators estimate that ten patients in each arm will generate a basis for determining if there is sufficient signal for AII to improve blood pressure at the doses outlined. The primary endpoint in the study will be the effect of AII on the standing dose of norepinephrine which is required to maintain a mean arterial pressure (MAP) of 65 mmHg. Secondary endpoints will be the effect of AII on urine output, serum lactate, and creatinine clearance. 30 day post dose mortality will also be assessed. Subjects discharged prior to day 30 will be contacted by telephone for this assessment.

Conditions

Septic Shock

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Angiotensin

The angiotensin arm will receive angiotensin II acetate at an initial dose of 20ng/kg/min, titratable during the study (6 hours) for mean arterial pressure (MAP) goals as outlined in the protocol.

Group Type: ACTIVE_COMPARATOR

Angiotensin II

Intervention Type: DRUG

All patients will have their vasopressors titrated to a mean arterial pressure (MAP) of 65 mm of Hg (standard MAP goal in the ICU for patients suffering from shock). Patients will then be randomized to control or IV AII. In the interventional arm, AII will start at a dose of 20ng/kg/min; the dose can then be titrated up to 30ng/kg/min, and then to 40ng/kg/min. The intervention will last for 6 hours. Each patient will start with the assigned starting dose indicated above. After the first hour, if the patient is still requiring standing norepinephrine (the standard vasopressor for the treatment of shock in the GW ICU), the dose of the control/interventional drug can be increased 50%. After the second hour, if the patient is still requiring a standing dose of norepinephrine, the control/interventional can be increased again to twice the initial dose. At the end of 6 hours, the study drug will be titrated off.

Control

Control patients will receive placebo intravenously equal in duration, color and volume to the intervention arm's angiotensin II.

Group Type: PLACEBO_COMPARATOR

Angiotensin II

Intervention Type: DRUG

All patients will have their vasopressors titrated to a mean arterial pressure (MAP) of 65 mm of Hg (standard MAP goal in the ICU for patients suffering from shock). Patients will then be randomized to control or IV AII. In the interventional arm, AII will start at a dose of 20ng/kg/min; the dose can then be titrated up to 30ng/kg/min, and then to 40ng/kg/min. The intervention will last for 6 hours. Each patient will start with the assigned starting dose indicated above. After the first hour, if the patient is still requiring standing norepinephrine (the standard vasopressor for the treatment of shock in the GW ICU), the dose of the control/interventional drug can be increased 50%. After the second hour, if the patient is still requiring a standing dose of norepinephrine, the control/interventional can be increased again to twice the initial dose. At the end of 6 hours, the study drug will be titrated off.

Interventions

Angiotensin II

All patients will have their vasopressors titrated to a mean arterial pressure (MAP) of 65 mm of Hg (standard MAP goal in the ICU for patients suffering from shock). Patients will then be randomized to control or IV AII. In the interventional arm, AII will start at a dose of 20ng/kg/min; the dose can then be titrated up to 30ng/kg/min, and then to 40ng/kg/min. The intervention will last for 6 hours. Each patient will start with the assigned starting dose indicated above. After the first hour, if the patient is still requiring standing norepinephrine (the standard vasopressor for the treatment of shock in the GW ICU), the dose of the control/interventional drug can be increased 50%. After the second hour, if the patient is still requiring a standing dose of norepinephrine, the control/interventional can be increased again to twice the initial dose. At the end of 6 hours, the study drug will be titrated off.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. High-output shock

2. Cardiovascular SOFA score of > 4

3. Cardiac Index > 2.4 liters/min/BSA 1.73m2

4. Indwelling arterial line already present as part of standard care

5. Age > 21 years of age

6. Signed consent form

7. Use of indwelling urinary catheter as standard care expected at least for 12 hours during the study interventions

Exclusion Criteria

1. Patients with acute coronary syndrome

2. Patients with a known history of vasospasm

3. Patients with a history of asthma

4. Patients currently experiencing bronchospasm

5. Patients with active bleeding with an anticipated need for > 4 units of PRBC or Hemoglobin < 7g/dL or any other condition that would contraindicate drawing serial blood samples

• Minimum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

George Washington University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lakhmir Chawla, MD

Role: PRINCIPAL_INVESTIGATOR

GW University

Locations

GW University

Washington D.C., District of Columbia, United States

Countries

United States

References

Chawla LS, Busse L, Brasha-Mitchell E, Davison D, Honiq J, Alotaibi Z, Seneff MG. Intravenous angiotensin II for the treatment of high-output shock (ATHOS trial): a pilot study. Crit Care. 2014 Oct 6;18(5):534. doi: 10.1186/s13054-014-0534-9.

Reference Type: DERIVED

PMID: 25286986 (View on PubMed)

Other Identifiers

111016

Identifier Type: -

Identifier Source: org_study_id