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

Phase 1

Completed

Conditions: Septic Shock

Interventions: Drug: Angiotensin II

Registration Number: NCT01393782

Lead Sponsor: George Washington University

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 20

Inclusion Criteria

High-output shock
Cardiovascular SOFA score of > 4
Cardiac Index > 2.4 liters/min/BSA 1.73m2
Indwelling arterial line already present as part of standard care
Age > 21 years of age
Signed consent form
Use of indwelling urinary catheter as standard care expected at least for 12 hours during the study interventions

Exclusion Criteria

Patients with acute coronary syndrome
Patients with a known history of vasospasm
Patients with a history of asthma
Patients currently experiencing bronchospasm
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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Standing Dose of Norepinephrine Which is Required to Maintain a MAP of 65 mmHg - Hour 2	2 hours after initiation of ATII	The primary endpoint in the study will be the effect of AII on the standing dose of norepinephrine which is required to maintain a MAP of 65 mmHg.
Standing Dose of Norepinephrine Which is Required to Maintain a Mean Arterial Pressure (MAP) of 65 mmHg - Hour 1	1 hour after initiation of angiotensin II (ATII)	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 Outcome Measures