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Treatment of Angiotensin Converting Enzyme Inhibitor-induced Angioedema

Primary Purpose

Angioedema Caused by Angiotensin-Converting-Enzyme Inhibitor

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
High ACE Activity Fresh Frozen Plasma
Normal Saline
Sponsored by
Washington University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Angioedema Caused by Angiotensin-Converting-Enzyme Inhibitor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Barnes-Jewish Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

High ACE Activity Fresh Frozen Plasma

Normal Saline

Arm Description

Subjects will be treated with 2 units of fresh frozen plasma that have been preselected to contain ACE activity ≥50 U/L

Subjects will be treated with normal saline 500 cc.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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
Sustained change in serum ACE activity with treatment
Determine if treatment results in a sustained change in ACE activity levels

Full Information

First Posted
December 15, 2020
Last Updated
May 23, 2023
Sponsor
Washington University School of Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT04679311
Brief Title
Treatment of Angiotensin Converting Enzyme Inhibitor-induced Angioedema
Official Title
High Angiotensin Converting Enzyme Activity-containing Plasma for the Treatment of Angiotensin Converting Enzyme Inhibitor-induced Angioedema
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Terminated
Why Stopped
End of funding period
Study Start Date
December 22, 2020 (Actual)
Primary Completion Date
January 31, 2023 (Actual)
Study Completion Date
January 31, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Angioedema Caused by Angiotensin-Converting-Enzyme Inhibitor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Masking Description
The laboratory that performs the assays and the assessor of the angioedema will be blinded to the treatment the subject received.
Allocation
Randomized
Enrollment
3 (Actual)

8. Arms, Groups, and Interventions

Arm Title
High ACE Activity Fresh Frozen Plasma
Arm Type
Experimental
Arm Description
Subjects will be treated with 2 units of fresh frozen plasma that have been preselected to contain ACE activity ≥50 U/L
Arm Title
Normal Saline
Arm Type
Placebo Comparator
Arm Description
Subjects will be treated with normal saline 500 cc.
Intervention Type
Biological
Intervention Name(s)
High ACE Activity Fresh Frozen Plasma
Intervention Description
Subjects will be treated with fresh frozen plasma that has been preselected for ACE activity content of ≥ 50 U/L
Intervention Type
Other
Intervention Name(s)
Normal Saline
Intervention Description
Subjects will be treated with normal saline 500 cc
Primary Outcome Measure Information:
Title
Determine if treatment with 2 units of fresh frozen plasma that contains ≥ 50 U/L of ACE activity increases serum ACE activity
Description
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
Time Frame
Compare serum ACE activity before treatment and 30 minutes after treatment
Secondary Outcome Measure Information:
Title
Determine how treatment affects the severity of angioedema using a published validated clinical rating scale
Description
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
Time Frame
Compare angioedema severity before treatment and 30 minutes, 2 hours, and 8 hours after treatment
Title
Sustained change in serum ACE activity with treatment
Description
Determine if treatment results in a sustained change in ACE activity levels
Time Frame
Compare serum ACE activity before treatment and at 2 hours and 8 hours after treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steven J Weintraub, M.D.
Organizational Affiliation
Washington University School of Medicine and the St. Louis VA Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Barnes-Jewish Hospital
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
30836229
Citation
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.
Results Reference
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Treatment of Angiotensin Converting Enzyme Inhibitor-induced Angioedema

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