Clinical trial NCT01393782: Intravenous AII for the Treatment of Severe Hypotension in High Output Shock: A Pilot Study
Official title: Intravenous AII for the Treatment of Severe Hypotension in High Output Shock: A Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Septic Shock
Keywords: high output shock
distributive shock
warm shock
septic shock
pressor
angiotensin
ATII
vasopressor
Lead sponsor: George Washington University
Sponsor class: OTHER
First posted: 2011-07-13
Enrollment: 20
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Standing Dose of Norepinephrine Which is Required to Maintain a Mean Arterial Pressure (MAP) of 65 mmHg - Hour 1
timeFrame: 1 hour after initiation of angiotensin II (ATII)
measure: Standing Dose of Norepinephrine Which is Required to Maintain a MAP of 65 mmHg - Hour 2
timeFrame: 2 hours after initiation of ATII
Secondary outcomes:
measure: Mortality
timeFrame: 30 days
Other outcomes:
Locations:
city: Washington
country: United States
facility: GW University
state: District of Columbia
Study officials:
affiliation: GW University
name: Lakhmir Chawla, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.