Treatment of Angiotensin Converting Enzyme Inhibitor-induced Angioedema

NCT ID: NCT04679311

Last Updated: 2024-03-27

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-22
• Study Completion Date: 2023-01-31

Brief Summary

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.

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.

Conditions

Angioedema Caused by Angiotensin-Converting-Enzyme Inhibitor

Study Design

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

Study Groups

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

Group Type: EXPERIMENTAL

High ACE Activity Fresh Frozen Plasma

Intervention Type: BIOLOGICAL

Subjects will be treated with fresh frozen plasma that has been preselected for ACE activity content of ≥ 50 U/L

Normal Saline

Subjects will be treated with normal saline 500 cc.

Group Type: PLACEBO_COMPARATOR

Normal Saline

Intervention Type: OTHER

Subjects will be treated with normal saline 500 cc

Interventions

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

Intervention Type: BIOLOGICAL

Normal Saline

Subjects will be treated with normal saline 500 cc

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Steven J Weintraub, M.D.

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine and the St. Louis VA Medical Center

Locations

Barnes-Jewish Hospital

St Louis, Missouri, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 30836229 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

202002126

Identifier Type: -

Identifier Source: org_study_id