ACE Inhibitor-Induced AngioedemaPhase 3NCT06679426
Safety and Efficacy of Conestat Alfa for ACE-Induced Angioedema
A Phase 3 study testing Conestat Alfa in people with ACE Inhibitor-Induced Angioedema, run by University of Cincinnati.
Trial summary
Angiotensin-converting enzyme inhibitors (ACE-Is), prescribed most often to treat hypertension, have been used extensively since the 1980s. Additional indications for their use include heart failure, diabetes mellitus, chronic kidney disease, and post-myocardial infarction. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- ACE Inhibitor-Induced Angioedema
- What is being tested?
- Conestat Alfa
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- No sites listed yet
- Study dates
- 1 Dec 2024to Dec 2025
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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
- 1. Age 18 years or older 2. Currently being treated with an ACE-I and presenting with presumed ACE-I-induced AE involving the head and/or neck region as determined by the clinical team 3. ACE-I-induced AE of the head and/or neck region of at least moderate severity within 24 hours of onset (must be sufficiently less than 24 hours to allow study drug to be administered within the same time frame) 4. AE that is at least moderate in severity for no less than one of the AE-associated airway symptoms (difficulty breathing, difficulty swallowing, voice changes, tongue swelling)32 5. Be able to provide informed consent or obtain informed consent from a legally appointed representative
- -
Who cannot join
- 1. History of anaphylaxis, hypersensitivity, or allergic reactions to rabbits/rabbit-derived products and C1-INH preparations 2. Urticaria present during the current illness 3. AE thought by the clinical team to be due to any other etiology i.e., HAE (types I, II, and HAE with normal C1-INH), acquired AE, allergic/histaminergic AE 4. History of recent trauma, abscess, infection, local inflammation, local tumor, postoperative or post-radiogenic edema, salivary gland disorders, and non-ACE-I drug-induced AE 5. Family history of recurrent AE 6. History of AE prior to ACE-I therapy initiation 7. Last dose of ACE-I taken more than 72 hours before the onset of AE symptoms 8. History of a major systemic disease that is not well controlled (left to the study team's discretion) 9. Anyone requiring immediate airway intervention according to the clinical team, such as endotracheal intubation 10. Women who are pregnant or breast-feeding (pregnancy must be ruled out by a negative test with the exception of those who have undergone total hysterectomy, bilateral oophorectomy, or are 2 years post-menopausal) 11. Concurrent participation in other investigational drug studies 12. Treatment with other targeted therapeutic agents for HAE (ecallantide/icatibant/C1-INH/fresh frozen plasma) 13. In the opinion of the investigator, there is adequate response to the usual care treatments (epinephrine, H1 and/or H2 antihistamine, corticosteroids) within one hour before dosing of the study drug 14. Prisoners 15. Non-English speaking
- -
Trial locations and contacts
No sites are listed yet.
About this study
Official title: A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Clinical Study Evaluating the Safety and Efficacy of Conestat Alfa As a Treatment for Angiotensin-Converting Enzyme-Inhibitor-Induced Angioedema
Angiotensin-converting enzyme inhibitors (ACE-Is), prescribed most often to treat hypertension, have been used extensively since the 1980s. Additional indications for their use include heart failure, diabetes mellitus, chronic kidney disease, and post-myocardial infarction. It is estimated that up to 40 million patients take ACE-Is worldwide. C1-INH is a serine protease inhibitor that is normally found in the blood. Its primary function is the regulation of the complement and contact system pathways by binding irreversibly to target proteases. It additionally inhibits the fibrinolytic, clotting, and kinin pathways.31 Patients with the hereditary forms of AE (HAE) tend to have lower quantitative or functional levels of C1-INH. This results in decreased suppression of plasma kallikrein and factor XIIa leading to cleavage of high molecular weight kininogen to form increased circulating levels of bradykinin. Bradykinin binds to bradykinin 2 receptors resulting in separation of endothelial vascular cells and extravasation of fluid manifesting clinically as angioedema. Conestat alfa (Ruconest®) is a recombinant human C1-INH that has been purified from the breast milk of genetically modified rabbits. It is a single-chain soluble glycoprotein that is made of 478 amino acids. Administering conestat alfa increases the amount of C1-INH in these patients, repleting their levels, and acting as a treatment for AE due to C1-INH deficiency. Conestat alfa has been studied on asymptomatic patients with HAE and was shown to dose-dependently increase the level of functional C1-INH. Additionally, it was shown to restore the level of the complement C4 protein, which is also decreased in these patients. Since the same pathophysiological pathway is involved in patients with ACE-I-induced AE, it is reasonable to hypothesize its effectiveness in the treatment of patients with acute attacks.
Read the detailed description
This phase III clinical trial is being conducted to assess the benefits of emergency administration of intravenous (IV) conestat alfa to treat ACE-I-induced AE during an ED visit. This will be a multi-center, randomized, double-blind, two-armed, placebo-controlled trial. It will enroll 24 patients at two clinical sites in the United States. The population will consist of adult patients (≥ 18 years of age) who present to the ED with acute ACE-I-induced AE of the head and/or neck. Eligible patients will be enrolled in the study and randomized at a ratio of 1:1 to either the active treatment or placebo groups. The treatment group will receive intravenous conestat alfa at a fixed dose of 4200 International Units (IU) IV along with usual ED care at the discretion of the clinical care team, which may include epinephrine, H1 and/or H2-antihistamines, and corticosteroids. The placebo group will receive the same volume of an isotonic, sterile, normal saline (pH 5.5 ± 0.3) solution without any preservatives via IV injection, in addition to the usual care. Fixed dosing was chosen for this study rather than weight-based dosing as is used for treatment of acute attacks of hereditary angioedema because it is hypothesized that higher doses may have greater efficacy in ACE-I-induced AE and is safe to administer.32 A second fixed dose (4200 IU) of open label study drug will be administered 2 hours after the initial dose as a rescue medication if the subject has not experienced symptom relief (based upon TOSR evaluation). Additional doses of study drug or placebo will not be used. The rationale behind the dosage is based on the fact that 4200 IU is the maximum dose irrespective of patient weight. A second dose of the same amount is recommended if symptoms persist.
The primary objective is to compare the Time to Onset of Symptom Relief (TOSR) of conestat alfa compared to placebo in the treatment of ACE-I-induced AE. The secondary objective is to evaluate the efficacy of conestat alfa compared to placebo in Time to Meeting Discharge Criteria (TMDC), based on investigator-assessment of upper airway symptoms. The study will also compare the proportion of patients in each arm who 1) are hospitalized for any level of care 2) are admitted to the intensive care unit (ICU) and 3) requiring airway intervention (e.g., intubation, cricothyrotomy, or tracheotomy). Safety and tolerability of conestat alfa treatment will also be assessed.
- Conditions
- ACE Inhibitor-Induced Angioedema
- Being tested
- Conestat Alfa
- Keywords
- Ruconest, conestat alpha, ACE inhibitor, angioedema, treatment, outcome, safety
- Medical subject headings
- Angioedema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Conestat AlfaDrug
Also called Ruconest
See arm/group descriptions
| Study group | Role | What they receive |
|---|---|---|
| Investigational product | Active comparator | Human recombinant C1-INH, also known as conestat alfa (Ruconest™), has been purified from the breast milk of genetically modified rabbits. Conestat alfa targets activated C1s, kallikrein, factor XIIa, and factor XIa. Inhibition kinetics are comparable to plasma-derived human C1-INH. The elimination half-life is approximately 2.5 hours.37 One vial consists of 2100 units, which corresponds to 2100 units per 14 mL after reconstitution, resulting in a concentration of 150 units/mL. One unit of activity corresponds to C1 esterase inhibiting activity in 1 mL of normal plasma. Each vial also contains 19.5 mg of sodium.41 In order to administer 4200 IU of conestat alfa, 2 reconstituted vials are needed Receives: Drug: Conestat Alfa |
| Placebo | Placebo comparator | The comparator in the study will be a placebo, an isotonic sterile solution (pH 5.5 ± 0.3) for IV injection. The solution does not contain any preservatives. The placebo is formulated to match the study drug (conestat alfa) and is supplied in an identical single-dose IV bag. To maintain the blinding of the study, the IV bag containing the placebo will be indistinguishable from that containing conestat alfa, in addition to the labeling Receives: Drug: Conestat Alfa |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary objective is to assess the efficacy of conestat alfa compared to placebo in the treatment of ACE-1-induced AE based on the Time to Onset of Symptom Relief (TOSR) endpoint.
The TOSR is defined as the time at which the total severity score of four airway compromising symptoms (difficulty breathing, difficulty swallowing, voice changes, and tongue swelling) has decreased by at least 1 point overall and no individual component of the score has increased. The 5-point severity scale is: 0 = absence of symptoms, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe.
Measured: 24 hours
Secondary outcomes (1)
The secondary objective is to compare the efficacy of conestat alfa to placebo for the treatment of ACE-1-induced AE based on the endpoint of Time to Meeting Discharge Criteria (TMDC).
The criteria for discharge will be based on the assessment of the severity of four airway compromising symptoms, and will be calculated from the time of initiation of study drug administration to the earliest point at which the symptoms of difficulty breathing and difficulty swallowing have resolved (score = 0) and the symptoms of voice change and tongue swelling are mild or absent.
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2024
- Study start1 Dec 2024 (estimated)
- Primary completionDec 2025 (estimated)
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for ACE Inhibitor-Induced AngioedemaStudies of the same condition, open and under way.
- More trials run by University of CincinnatiThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This Phase III study is designed as a randomized, double-blind, two-armed, placebo-controlled study (Figure 2). It will be conducted at two centers in the United States. The primary aim is to compare the efficacy of conestat alfa with a placebo in the treatment of ACE-I-induced AE based on the TMDC endpoint, assess its safety and tolerability, as well as compare its efficacy compared to the placebo based on the TOSR endpoint. Moreover, the proportion of patients in each arm who are hospitalized, admitted to the ICU, or who require an airway intervention will be compared.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Cincinnati
- Sponsor type
- University, hospital or other
- Collaborators
- University of Maryland
- Responsible party
- Principal investigator, Jonathan Bernstein, University of Cincinnati
- Investigators
- Joseph A. Moellman, MD, Principal investigator, University of CincinnatiGentry Wilkerson, MD, Principal investigator, University of Maryland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06679426
- Sponsor's protocol ID
- 2024-0561
- Status last verified
- Jul 2024
- First submitted
- 5 Nov 2024
- Last updated
- 7 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data will be published. Raw data will be provided upon request as appropriate.
Publications
Bernstein JA, Moellman JJ, Collins SP, Hart KW, Lindsell CJ. Effectiveness of ecallantide in treating angiotensin-converting enzyme inhibitor-induced angioedema in the emergency department. Ann Allergy Asthma Immunol. 2015 Mar;114(3):245-9. doi: 10.1016/j.anai.2014.12.007. Epub 2015 Jan 16.
PubMed 25601538Moellman JJ, Bernstein JA, Lindsell C, Banerji A, Busse PJ, Camargo CA Jr, Collins SP, Craig TJ, Lumry WR, Nowak R, Pines JM, Raja AS, Riedl M, Ward MJ, Zuraw BL, Diercks D, Hiestand B, Campbell RL, Schneider S, Sinert R; American College of Allergy, Asthma & Immunology (ACAAI); Society for Academic Emergency Medicine (SAEM). A consensus parameter for the evaluation and management of angioedema in the emergency department. Acad Emerg Med. 2014 Apr;21(4):469-84. doi: 10.1111/acem.12341.
PubMed 24730413Bonner N, Panter C, Kimura A, Sinert R, Moellman J, Bernstein JA. Development and validation of the angiotensin-converting enzyme inhibitor (ACEI) induced angioedema investigator rating scale and proposed discharge criteria. BMC Health Serv Res. 2017 May 22;17(1):366. doi: 10.1186/s12913-017-2274-4.
PubMed 28532495Sinert R, Levy P, Bernstein JA, Body R, Sivilotti MLA, Moellman J, Schranz J, Baptista J, Kimura A, Nothaft W; CAMEO study group. Randomized Trial of Icatibant for Angiotensin-Converting Enzyme Inhibitor-Induced Upper Airway Angioedema. J Allergy Clin Immunol Pract. 2017 Sep-Oct;5(5):1402-1409.e3. doi: 10.1016/j.jaip.2017.03.003. Epub 2017 May 25.
PubMed 28552382Mudd PA, Hooker EA, Stolz U, Hart KW, Bernstein JA, Moellman JJ. Emergency department evaluation of patients with angiotensin converting enzyme inhibitor associated angioedema. Am J Emerg Med. 2020 Dec;38(12):2596-2601. doi: 10.1016/j.ajem.2019.12.058. Epub 2020 Jan 7.
PubMed 31932133Wilkerson RG, Dakessian A, Moellman JJ, Bernstein JA. Clinical trial of C1-INH for treatment of ACEi-induced angioedema. Am J Emerg Med. 2023 Jun;68:196-197. doi: 10.1016/j.ajem.2023.04.012. Epub 2023 Apr 11. No abstract available.
PubMed 37061431
Study at a glance
From the registry record, last updated by the sponsor on 7 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Clinical Study Evaluating the Safety and Efficacy of Conestat Alfa As a Treatment for Angiotensin-Converting Enzyme-Inhibitor-Induced Angioedema
- ClinicalTrials.gov ID
- NCT06679426
- Acronym / sponsor ID
- 2024-0561
- Conditions
- ACE Inhibitor-Induced Angioedema
- Keywords
- Ruconest, conestat alpha, ACE inhibitor, angioedema, treatment, outcome, safety
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- University of CincinnatiUniversity, hospital or other
- Collaborators
- University of Maryland
- Study start
- 1 Dec 2024 (estimated)
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 7 Nov 2024 (actual)
- Results
- Not posted in the source record
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 inhibitors (ACE-Is), prescribed most often to treat hypertension, have been used extensively since the 1980s. Additional indications for their use include heart failure, diabetes mellitus, chronic kidney disease, and post-myocardial infarction. It is estimated that up to 40 million patients take ACE-Is worldwide. C1-INH is a serine protease inhibitor that is normally found in the blood. Its primary function is the regulation of the complement and contact system pathways by binding irreversibly to target proteases. It additionally inhibits the fibrinolytic, clotting, and kinin pathways.31 Patients with the hereditary forms of AE (HAE) tend to have lower quantitative or functional levels of C1-INH. This results in decreased suppression of plasma kallikrein and factor XIIa leading to cleavage of high molecular weight kininogen to form increased circulating levels of bradykinin. Bradykinin binds to bradykinin 2 receptors resulting in separation of endothelial vascular cells and extravasation of fluid manifesting clinically as angioedema. Conestat alfa (Ruconest®) is a recombinant human C1-INH that has been purified from the breast milk of genetically modified rabbits. It is a single-chain soluble glycoprotein that is made of 478 amino acids. Administering conestat alfa increases the amount of C1-INH in these patients, repleting their levels, and acting as a treatment for AE due to C1-INH deficiency. Conestat alfa has been studied on asymptomatic patients with HAE and was shown to dose-dependently increase the level of functional C1-INH. Additionally, it was shown to restore the level of the complement C4 protein, which is also decreased in these patients. Since the same pathophysiological pathway is involved in patients with ACE-I-induced AE, it is reasonable to hypothesize its effectiveness in the treatment of patients with acute attacks.
Detailed description
This phase III clinical trial is being conducted to assess the benefits of emergency administration of intravenous (IV) conestat alfa to treat ACE-I-induced AE during an ED visit. This will be a multi-center, randomized, double-blind, two-armed, placebo-controlled trial. It will enroll 24 patients at two clinical sites in the United States. The population will consist of adult patients (≥ 18 years of age) who present to the ED with acute ACE-I-induced AE of the head and/or neck. Eligible patients will be enrolled in the study and randomized at a ratio of 1:1 to either the active treatment or placebo groups. The treatment group will receive intravenous conestat alfa at a fixed dose of 4200 International Units (IU) IV along with usual ED care at the discretion of the clinical care team, which may include epinephrine, H1 and/or H2-antihistamines, and corticosteroids. The placebo group will receive the same volume of an isotonic, sterile, normal saline (pH 5.5 ± 0.3) solution without any preservatives via IV injection, in addition to the usual care. Fixed dosing was chosen for this study rather than weight-based dosing as is used for treatment of acute attacks of hereditary angioedema because it is hypothesized that higher doses may have greater efficacy in ACE-I-induced AE and is safe to administer.32 A second fixed dose (4200 IU) of open label study drug will be administered 2 hours after the initial dose as a rescue medication if the subject has not experienced symptom relief (based upon TOSR evaluation). Additional doses of study drug or placebo will not be used. The rationale behind the dosage is based on the fact that 4200 IU is the maximum dose irrespective of patient weight. A second dose of the same amount is recommended if symptoms persist.
The primary objective is to compare the Time to Onset of Symptom Relief (TOSR) of conestat alfa compared to placebo in the treatment of ACE-I-induced AE. The secondary objective is to evaluate the efficacy of conestat alfa compared to placebo in Time to Meeting Discharge Criteria (TMDC), based on investigator-assessment of upper airway symptoms. The study will also compare the proportion of patients in each arm who 1) are hospitalized for any level of care 2) are admitted to the intensive care unit (ICU) and 3) requiring airway intervention (e.g., intubation, cricothyrotomy, or tracheotomy). Safety and tolerability of conestat alfa treatment will also be assessed.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- This Phase III study is designed as a randomized, double-blind, two-armed, placebo-controlled study (Figure 2). It will be conducted at two centers in the United States. The primary aim is to compare the efficacy of conestat alfa with a placebo in the treatment of ACE-I-induced AE based on the TMDC endpoint, assess its safety and tolerability, as well as compare its efficacy compared to the placebo based on the TOSR endpoint. Moreover, the proportion of patients in each arm who are hospitalized, admitted to the ICU, or who require an airway intervention will be compared.
| Arm | Type | Receives |
|---|---|---|
| Investigational product | Active comparator | Drug: Conestat AlfaHuman recombinant C1-INH, also known as conestat alfa (Ruconest™), has been purified from the breast milk of genetically modified rabbits. Conestat alfa targets activated C1s, kallikrein, factor XIIa, and factor XIa. Inhibition kinetics are comparable to plasma-derived human C1-INH. The elimination half-life is approximately 2.5 hours.37 One vial consists of 2100 units, which corresponds to 2100 units per 14 mL after reconstitution, resulting in a concentration of 150 units/mL. One unit of activity corresponds to C1 esterase inhibiting activity in 1 mL of normal plasma. Each vial also contains 19.5 mg of sodium.41 In order to administer 4200 IU of conestat alfa, 2 reconstituted vials are needed |
| Placebo | Placebo comparator | Drug: Conestat AlfaThe comparator in the study will be a placebo, an isotonic sterile solution (pH 5.5 ± 0.3) for IV injection. The solution does not contain any preservatives. The placebo is formulated to match the study drug (conestat alfa) and is supplied in an identical single-dose IV bag. To maintain the blinding of the study, the IV bag containing the placebo will be indistinguishable from that containing conestat alfa, in addition to the labeling |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 1. Age 18 years or older 2. Currently being treated with an ACE-I and presenting with presumed ACE-I-induced AE involving the head and/or neck region as determined by the clinical team 3. ACE-I-induced AE of the head and/or neck region of at least moderate severity within 24 hours of onset (must be sufficiently less than 24 hours to allow study drug to be administered within the same time frame) 4. AE that is at least moderate in severity for no less than one of the AE-associated airway symptoms (difficulty breathing, difficulty swallowing, voice changes, tongue swelling)32 5. Be able to provide informed consent or obtain informed consent from a legally appointed representative
- -
Key exclusion criteria (2 listed)
- 1. History of anaphylaxis, hypersensitivity, or allergic reactions to rabbits/rabbit-derived products and C1-INH preparations 2. Urticaria present during the current illness 3. AE thought by the clinical team to be due to any other etiology i.e., HAE (types I, II, and HAE with normal C1-INH), acquired AE, allergic/histaminergic AE 4. History of recent trauma, abscess, infection, local inflammation, local tumor, postoperative or post-radiogenic edema, salivary gland disorders, and non-ACE-I drug-induced AE 5. Family history of recurrent AE 6. History of AE prior to ACE-I therapy initiation 7. Last dose of ACE-I taken more than 72 hours before the onset of AE symptoms 8. History of a major systemic disease that is not well controlled (left to the study team's discretion) 9. Anyone requiring immediate airway intervention according to the clinical team, such as endotracheal intubation 10. Women who are pregnant or breast-feeding (pregnancy must be ruled out by a negative test with the exception of those who have undergone total hysterectomy, bilateral oophorectomy, or are 2 years post-menopausal) 11. Concurrent participation in other investigational drug studies 12. Treatment with other targeted therapeutic agents for HAE (ecallantide/icatibant/C1-INH/fresh frozen plasma) 13. In the opinion of the investigator, there is adequate response to the usual care treatments (epinephrine, H1 and/or H2 antihistamine, corticosteroids) within one hour before dosing of the study drug 14. Prisoners 15. Non-English speaking
- -
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 |
|---|---|---|
| Conestat AlfaAlso: RuconestSee arm/group descriptions | Drug | Investigational product, Placebo |
Primary outcome
The primary objective is to assess the efficacy of conestat alfa compared to placebo in the treatment of ACE-1-induced AE based on the Time to Onset of Symptom Relief (TOSR) endpoint.
Time frame: 24 hours
The TOSR is defined as the time at which the total severity score of four airway compromising symptoms (difficulty breathing, difficulty swallowing, voice changes, and tongue swelling) has decreased by at least 1 point overall and no individual component of the score has increased. The 5-point severity scale is: 0 = absence of symptoms, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe.
1 secondary outcome
The secondary objective is to compare the efficacy of conestat alfa to placebo for the treatment of ACE-1-induced AE based on the endpoint of Time to Meeting Discharge Criteria (TMDC).
Time frame: 24 hours
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Nov 2024.
- Background: PubMed 25601538Bernstein JA, Moellman JJ, Collins SP, Hart KW, Lindsell CJ. Effectiveness of ecallantide in treating angiotensin-converting enzyme inhibitor-induced angioedema in the emergency department. Ann Allergy Asthma Immunol. 2015 Mar;114(3):245-9. doi: 10.1016/j.anai.2014.12.007. Epub 2015 Jan 16.
- Background: PubMed 24730413Moellman JJ, Bernstein JA, Lindsell C, Banerji A, Busse PJ, Camargo CA Jr, Collins SP, Craig TJ, Lumry WR, Nowak R, Pines JM, Raja AS, Riedl M, Ward MJ, Zuraw BL, Diercks D, Hiestand B, Campbell RL, Schneider S, Sinert R; American College of Allergy, Asthma & Immunology (ACAAI); Society for Academic Emergency Medicine (SAEM). A consensus parameter for the evaluation and management of angioedema in the emergency department. Acad Emerg Med. 2014 Apr;21(4):469-84. doi: 10.1111/acem.12341.
- Background: PubMed 28532495Bonner N, Panter C, Kimura A, Sinert R, Moellman J, Bernstein JA. Development and validation of the angiotensin-converting enzyme inhibitor (ACEI) induced angioedema investigator rating scale and proposed discharge criteria. BMC Health Serv Res. 2017 May 22;17(1):366. doi: 10.1186/s12913-017-2274-4.
- Background: PubMed 28552382Sinert R, Levy P, Bernstein JA, Body R, Sivilotti MLA, Moellman J, Schranz J, Baptista J, Kimura A, Nothaft W; CAMEO study group. Randomized Trial of Icatibant for Angiotensin-Converting Enzyme Inhibitor-Induced Upper Airway Angioedema. J Allergy Clin Immunol Pract. 2017 Sep-Oct;5(5):1402-1409.e3. doi: 10.1016/j.jaip.2017.03.003. Epub 2017 May 25.
- Background: PubMed 31932133Mudd PA, Hooker EA, Stolz U, Hart KW, Bernstein JA, Moellman JJ. Emergency department evaluation of patients with angiotensin converting enzyme inhibitor associated angioedema. Am J Emerg Med. 2020 Dec;38(12):2596-2601. doi: 10.1016/j.ajem.2019.12.058. Epub 2020 Jan 7.
- Background: PubMed 37061431Wilkerson RG, Dakessian A, Moellman JJ, Bernstein JA. Clinical trial of C1-INH for treatment of ACEi-induced angioedema. Am J Emerg Med. 2023 Jun;68:196-197. doi: 10.1016/j.ajem.2023.04.012. Epub 2023 Apr 11. No abstract available.
- Individual participant dataSharing planned: Yes. Data will be published. Raw data will be provided upon request as appropriate.
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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.
Joseph A. Moellman, MD principal investigator
University of Cincinnati
Gentry Wilkerson, MD principal investigator
University of Maryland
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Conestat Alfa in people with ACE Inhibitor-Induced Angioedema, run by University of Cincinnati.
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 2 inclusion and 2 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: status not confirmed, as of the sponsor's last update on 7 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jonathan A. Bernstein, MD (5132357971, bernstja@ucmail.uc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary objective is to assess the efficacy of conestat alfa compared to placebo in the treatment of ACE-1-induced AE based on the Time to Onset of Symptom Relief (TOSR) endpoint. (time frame: 24 hours). 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 NCT06679426, which also lists 6 linked publications.
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 7 Nov 2024.