Treatment of Angiotensin Converting Enzyme Inhibitor-induced Angioedema

High Angiotensin Converting Enzyme Activity-containing Plasma for the Treatment of Angiotensin Converting Enzyme Inhibitor-induced Angioedema

Angiotensin Converting Enzyme (ACE) inhibitors are among the most important and widely prescribed drugs. They reduce the morbidity and mortality associated with high blood pressure, heart disease, and kidney disease. Unfortunately, their use carries the risk of causing life-threatening airway swelling in some patients. There is currently no treatment for this condition. A novel treatment approach that may reduce or completely reverse the swelling will be tested.

Study Overview

• Status: Terminated
• Conditions: Angioedema Caused by Angiotensin-Converting-Enzyme Inhibitor
• Intervention / Treatment: Biological: High ACE Activity Fresh Frozen Plasma; Other: Normal Saline

Detailed Description

The investigators will test the hypothesis that treatment with fresh frozen plasma that contains high levels of ACE activity will increase serum ACE activity and thereby cause the degradation of mediators of ACE inhibitor-induced angioedema, such as bradykinin and substance P, resulting in a shortening of the course of ACE inhibitor-induced angioedema.

16 patients with ACE inhibitor-induced angioedema will be randomized 1:1 to treatment with either 2 units of fresh frozen plasma that has been preselected for high ACE activity content (≥50 U/L) or an equal volume of normal saline. A baseline assessment of the severity of the angioedema will be performed and baseline serum levels of ACE activity will be determined. The severity of angioedema will be assessed and serum levels of ACE activity will be determined at specific intervals after each subject is treated.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Barnes-jewish Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Males and females 18 years of age or older
• Must currently be on ACE inhibitor therapy and have received a dose within 36 hours
• Presenting with moderate to severe angioedema affecting the upper aerodigestive tract (face, lips, cheeks, tongue, soft palate/uvula, pharynx, and larynx). The severity of the angioedema attack will be determined by the subject's worst severity rating at baseline among 4 clinical domains (difficulty breathing, difficulty swallowing, voice changes, and tongue swelling) based on a clinically validated angioedema severity scale29 (Table)
• Presenting with ACE inhibitor-induced angioedema within 12 hours after onset
• All females must have a locally obtained negative pregnancy test prior to administration of the study drug. Those who have had a total hysterectomy, bilateral oophorectomy, or are two years post-menopausal do not require a pregnancy test.
• Must be able to provide written informed consent to participate in the study to fulfill all study requirements

Exclusion Criteria:

• Pregnancy and/or breast feeding
• Patients with angioedema that is likely due to causes other than ACE inhibitors, including hereditary angioedema, acquired angioedema, and allergic angioedema (food, insect bite or sting with clear response to anti-allergy medications)
• Patients exhibiting acute urticaria
• Evident clinical response to glucocorticoids, antihistamines, or epinephrine
• A family history of recurrent angioedema
• Documented intolerance to plasma
• Documented congenital deficiency of immunoglobulin A in the presence of anti-immunoglobulin A antibodies
• Patients with heart failure of the severity that precludes safe transfusion of High ACE activity plasma
• Patients with acute pulmonary edema
• Patients with morbid obesity as defined by BMI>40; morbidly obese patients have a higher volume of blood needing higher amounts of plasma and therefore will be excluded from this pilot study
• Opinion of the investigator that the patient would not be a good candidate
• Participation in a clinical study in the past 30 days

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High ACE Activity Fresh Frozen Plasma; Subjects will be treated with 2 units of fresh frozen plasma that have been preselected to contain ACE activity ≥50 U/L	Biological: High ACE Activity Fresh Frozen Plasma; Subjects will be treated with fresh frozen plasma that has been preselected for ACE activity content of ≥ 50 U/L
Placebo Comparator: Normal Saline; Subjects will be treated with normal saline 500 cc.	Other: Normal Saline; Subjects will be treated with normal saline 500 cc

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine if Treatment With 2 Units of Fresh Frozen Plasma That Contains ≥ 50 U/L of ACE Activity Increases Serum ACE Activity	The subjects' serum ACE activity will be assessed prior to treatment and 30 minutes after treatment and compared to determine if the treatment increases serum ACE activity	Compare serum ACE activity before treatment and 30 minutes after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine How Treatment Affects the Severity of Angioedema Using a Published Validated Clinical Rating Scale	The severity of the the subjects' angioedema will be assessed using a published validated clinical rating scale before treatment and at 30 minutes, 2 hours, and 8 hours after treatment	Compare angioedema severity before treatment and 30 minutes, 2 hours, and 8 hours after treatment
Sustained Change in Serum ACE Activity With Treatment	Determine if treatment results in a sustained change in ACE activity levels	Compare serum ACE activity before treatment and at 2 hours and 8 hours after treatment

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Investigators: Principal Investigator: Steven J Weintraub, M.D., Washington University School of Medicine and the St. Louis VA Medical Center

Publications and helpful links

General Publications

• Chen SX, Hermelin D, Weintraub SJ. Possible donor-dependent differences in efficacy of fresh frozen plasma for treatment of ACE inhibitor-induced angioedema. J Allergy Clin Immunol Pract. 2019 Jul-Aug;7(6):2087-2088. doi: 10.1016/j.jaip.2019.02.027. Epub 2019 Mar 2. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2020
• Primary Completion (Actual): January 31, 2023
• Study Completion (Actual): January 31, 2023

Study Registration Dates

• First Submitted: December 15, 2020
• First Submitted That Met QC Criteria: December 21, 2020
• First Posted (Actual): December 22, 2020

Study Record Updates

• Last Update Posted (Actual): March 27, 2024
• Last Update Submitted That Met QC Criteria: February 28, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Skin Diseases, Vascular; Hypersensitivity; Urticaria; Angioedema
• Other Study ID Numbers: 202002126

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No