Treatment of Angiotensin Converting Enzyme Inhibitor-induced Angioedema

NCT04679311 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: 202002126
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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.

Conditions

Angioedema Caused by Angiotensin-Converting-Enzyme Inhibitor

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Determine How Treatment Affects the Severity of Angioedema Using a Published Validated Clinical Rating Scale

  Compare angioedema severity before treatment and 30 minutes, 2 hours, and 8 hours after treatment

• Sustained Change in Serum ACE Activity With Treatment

  Compare serum ACE activity before treatment and at 2 hours and 8 hours after treatment

Study Arms (2)

High ACE Activity Fresh Frozen Plasma

EXPERIMENTAL

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

Normal Saline

PLACEBO COMPARATOR

Subjects will be treated with normal saline 500 cc.

Other: Normal Saline

Interventions

High ACE Activity Fresh Frozen Plasma BIOLOGICAL

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

High ACE Activity Fresh Frozen Plasma

Normal Saline OTHER

Subjects will be treated with normal saline 500 cc

Normal Saline

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Barnes-Jewish Hospital

St Louis, Missouri, 63110, United States

Location

Related Publications (1)

• 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.

  PMID: 30836229 BACKGROUND

MeSH Terms

Interventions

Saline Solution

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Steven Weintraub MD
• Organization: Washington University School of Medicine

weintraub@wustl.edu

314-652-4100

Study Officials

• Steven J Weintraub, M.D.

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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The laboratory that performs the assays and the assessor of the angioedema will be blinded to the treatment the subject received.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2020
• First Posted: December 22, 2020
• Study Start: December 22, 2020
• Primary Completion: January 31, 2023
• Study Completion: January 31, 2023
• Last Updated: March 27, 2024
• Results First Posted: March 27, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)