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

George Washington University (GW)

Status and phase: Completed; Phase 1

Conditions: Septic Shock

Treatments: Drug: Angiotensin II

Study type: Interventional

Funder types: Other

Identifiers

NCT01393782

111016

Details and patient eligibility

About

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.

Enrollment: 20 patients

Sex: All

Ages: 21+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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20 participants in 2 patient groups, including a placebo group

Angiotensin

Active Comparator group

Description:

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.

Treatment:

Drug: Angiotensin II

Control

Placebo Comparator group

Description:

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

Treatment:

Drug: Angiotensin II