Angioedema Caused by Angiotensin-Converting-Enzyme InhibitorPhase 2NCT04679311
Treatment of Angiotensin Converting Enzyme Inhibitor-induced Angioedema
A Phase 2 study testing High ACE Activity Fresh Frozen Plasma and Normal Saline in people with Angioedema Caused by Angiotensin-Converting-Enzyme Inhibitor, run by Washington University School of Medicine at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Angioedema Caused by Angiotensin-Converting-Enzyme Inhibitor
- What is being tested?
- High ACE Activity Fresh Frozen Plasma and Normal Saline
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Dec 2020to 31 Jan 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Being tested
- High ACE Activity Fresh Frozen Plasma, Normal Saline
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High ACE Activity Fresh Frozen PlasmaBiological
Subjects will be treated with fresh frozen plasma that has been preselected for ACE activity content of ≥ 50 U/L
Normal SalineOther
Subjects will be treated with normal saline 500 cc
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Biological: High ACE Activity Fresh Frozen Plasma |
| Normal Saline | Placebo comparator | Subjects will be treated with normal saline 500 cc. Receives: Other: Normal Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
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
Measured: 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
Measured: Compare serum ACE activity before treatment and at 2 hours and 8 hours after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Dec 2020
- Study start22 Dec 2020
- Primary completion31 Jan 2023
- Study completion31 Jan 2023
Why it stopped: End of funding period
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Angioedema Caused by Angiotensin-Converting-Enzyme InhibitorStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Steven J Weintraub, M.D., Principal investigator, Washington University School of Medicine and the St. Louis VA Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04679311
- Sponsor's protocol ID
- 202002126
- Status last verified
- Feb 2024
- First submitted
- 15 Dec 2020
- Last updated
- 27 Mar 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 30836229
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- High Angiotensin Converting Enzyme Activity-containing Plasma for the Treatment of Angiotensin Converting Enzyme Inhibitor-induced Angioedema
- ClinicalTrials.gov ID
- NCT04679311
- Acronym / sponsor ID
- 202002126
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: End of funding period
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- 22 Dec 2020 (actual)
- Primary completion
- 31 Jan 2023 (actual)
- Study completion
- 31 Jan 2023 (actual)
- First posted
- 22 Dec 2020 (actual)
- Results
- Posted 27 Mar 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| High ACE Activity Fresh Frozen Plasma | Experimental | Biological: High ACE Activity Fresh Frozen PlasmaSubjects will be treated with 2 units of fresh frozen plasma that have been preselected to contain ACE activity ≥50 U/L |
| Normal Saline | Placebo comparator | Other: Normal SalineSubjects will be treated with normal saline 500 cc. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| High ACE Activity Fresh Frozen PlasmaSubjects will be treated with fresh frozen plasma that has been preselected for ACE activity content of ≥ 50 U/L | Biological | High ACE Activity Fresh Frozen Plasma |
| Normal SalineSubjects will be treated with normal saline 500 cc | Other | Normal Saline |
Primary outcome
Determine if Treatment With 2 Units of Fresh Frozen Plasma That Contains ≥ 50 U/L of ACE Activity Increases Serum ACE Activity
Time frame: Compare serum ACE activity before treatment and 30 minutes after treatment
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
2 secondary outcomes
Determine How Treatment Affects the Severity of Angioedema Using a Published Validated Clinical Rating Scale
Time frame: Compare angioedema severity before treatment and 30 minutes, 2 hours, and 8 hours after treatment
Sustained Change in Serum ACE Activity With Treatment
Time frame: Compare serum ACE activity before treatment and at 2 hours and 8 hours after treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 30836229Chen 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.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steven J Weintraub, M.D. principal investigator
Washington University School of Medicine and the St. Louis VA Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing High ACE Activity Fresh Frozen Plasma and Normal Saline in people with Angioedema Caused by Angiotensin-Converting-Enzyme Inhibitor, run by Washington University School of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 27 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Mar 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determine if Treatment With 2 Units of Fresh Frozen Plasma That Contains ≥ 50 U/L of ACE Activity Increases Serum ACE Activity (time frame: Compare serum ACE activity before treatment and 30 minutes after treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04679311, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2024.