Investigating the Efficacy and Safety ICATIBANT For The Treatment of Patients With SARS-CoV-2 (COVID-19) Infection

COVID-19 Pneumonia Clinical Trial

— ICAT·COVID  

Official title:

Randomized, Open, Multicenter Phase II Clinical Trial, Proof of Concept, to Evaluate Efficacy and Safety of Icatibant in Hospitalized Patients With SARS-COV-2 (COVID-19) Without Assisted Ventilation Compared With Standard Care

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04978051
• Other study ID #: HUB-MdI-ICAT·COVID-201
• Status: Completed
• Phase: Phase 2
• Start date: April 12, 2021
• Est. completion date: March 17, 2022

Study information

• Verified date: August 2022
• Source: Hospital Universitari de Bellvitge
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To study the efficacy and safety of icatibant in adult patients admitted to hospitalization units for pneumonia caused by COVID-19, without mechanical ventilation, 10±1 days after starting treatment or discharge from hospital if this occurs before 10 days.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 73
• Est. completion date: March 17, 2022
• Est. primary completion date: November 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. adult patients (18 years or older), both sexes

2. Sars-CoV-2 infection confirmed by PCR less than 4 days before randomization

3. hospitalized with a diagnosis of SARS-CoV-2 pneumonia

4. radiographic evidence of pulmonary infiltrates

5. grade 4 or 5 on the ordinal scale for the evaluation of the patient's clinical condition

6. pO2/FiO2 <380

7. men and women of childbearing age who have heterosexual relations must be agreement to use the safe method(s) of contraception

8. obtaining the informed consent of the patient or the legal representative.

Exclusion Criteria:

1. imminent death (life expectancy less than 72h)

2. known hypersensitivity or known adverse reactions to the study drug, or its metabolites or excipients of the formulation

3. invasive mechanical ventilation

4. participation in any other clinical trial

5. ALT or AST > 5 x ULN

6. creatinine clearance <50 mL/min using the Cockcroft-Gault formula for participants '18 years old [Cockcroft 1976]

7. patients with recent acute coronary syndrome (<1 month)

8. patients with a history of stroke

9. positive pregnancy test

10. pregnant or lactating woman

Related Conditions & MeSH terms

• COVID-19
• COVID-19 Pneumonia

Intervention

Drug:
• Firazyr
Icatibant 10 MG/ML Prefilled Syringe

Other:
• SoC
The SoC could include respiratory support measures, fluid therapy, antipyretic treatment, postural measures, low-molecular-weight-heparins, corticosteroids, such as dexamethasone, remdesivir and other therapeutic options

Locations

Country	Name	City	State
Spain	Hospital Universitari de Bellvitge	L'Hospitalet De Llobregat	Catalonia

Sponsors (1)

Lead Sponsor	Collaborator
Sebastian Videla

Country where clinical trial is conducted

Spain, 

References & Publications (14)

Bova M, Guilarte M, Sala-Cunill A, Borrelli P, Rizzelli GM, Zanichelli A. Treatment of ACEI-related angioedema with icatibant: a case series. Intern Emerg Med. 2015 Apr;10(3):345-50. doi: 10.1007/s11739-015-1205-9. Epub 2015 Feb 10. — View Citation

Busse PJ, Christiansen SC. Hereditary Angioedema. N Engl J Med. 2020 Mar 19;382(12):1136-1148. doi: 10.1056/NEJMra1808012. Review. — View Citation

Bygum A, Caballero T, Grumach AS, Longhurst HJ, Bouillet L, Aberer W, Zanichelli A, Botha J, Andresen I, Maurer M; IOS Study Group. Elderly versus younger patients with hereditary angioedema type I/II: patient characteristics and safety analysis from the Icatibant Outcome Survey. Clin Transl Allergy. 2019 Jul 19;9:37. doi: 10.1186/s13601-019-0272-9. eCollection 2019. — View Citation

Cicardi M, Banerji A, Bracho F, Malbrán A, Rosenkranz B, Riedl M, Bork K, Lumry W, Aberer W, Bier H, Bas M, Greve J, Hoffmann TK, Farkas H, Reshef A, Ritchie B, Yang W, Grabbe J, Kivity S, Kreuz W, Levy RJ, Luger T, Obtulowicz K, Schmid-Grendelmeier P, Bull C, Sitkauskiene B, Smith WB, Toubi E, Werner S, Anné S, Björkander J, Bouillet L, Cillari E, Hurewitz D, Jacobson KW, Katelaris CH, Maurer M, Merk H, Bernstein JA, Feighery C, Floccard B, Gleich G, Hébert J, Kaatz M, Keith P, Kirkpatrick CH, Langton D, Martin L, Pichler C, Resnick D, Wombolt D, Fernández Romero DS, Zanichelli A, Arcoleo F, Knolle J, Kravec I, Dong L, Zimmermann J, Rosen K, Fan WT. Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema. N Engl J Med. 2010 Aug 5;363(6):532-41. doi: 10.1056/NEJMoa0906393. Erratum in: N Engl J Med. 2010 Oct 7;363(15):1486. — View Citation

Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31-41. — View Citation

Hess R, Wujak L, Hesse C, Sewald K, Jonigk D, Warnecke G, Fieguth HG, de Maat S, Maas C, Bonella F, Preissner KT, Weiss B, Schaefer L, Kuebler WM, Markart P, Wygrecka M. Coagulation factor XII regulates inflammatory responses in human lungs. Thromb Haemost. 2017 Oct 5;117(10):1896-1907. doi: 10.1160/TH16-12-0904. Epub 2017 Aug 17. — View Citation

Jin YH, Cai L, Cheng ZS, Cheng H, Deng T, Fan YP, Fang C, Huang D, Huang LQ, Huang Q, Han Y, Hu B, Hu F, Li BH, Li YR, Liang K, Lin LK, Luo LS, Ma J, Ma LL, Peng ZY, Pan YB, Pan ZY, Ren XQ, Sun HM, Wang Y, Wang YY, Weng H, Wei CJ, Wu DF, Xia J, Xiong Y, Xu HB, Yao XM, Yuan YF, Ye TS, Zhang XC, Zhang YW, Zhang YG, Zhang HM, Zhao Y, Zhao MJ, Zi H, Zeng XT, Wang YY, Wang XH; , for the Zhongnan Hospital of Wuhan University Novel Coronavirus Management and Research Team, Evidence-Based Medicine Chapter of China International Exchange and Promotive Association for Medical and Health Care (CPAM). A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version). Mil Med Res. 2020 Feb 6;7(1):4. doi: 10.1186/s40779-020-0233-6. — View Citation

Leach JK, Spencer K, Mascelli M, McCauley TG. Pharmacokinetics of single and repeat doses of icatibant. Clin Pharmacol Drug Dev. 2015 Mar;4(2):105-11. doi: 10.1002/cpdd.138. Epub 2015 Feb 2. — View Citation

Siddiqi HK, Mehra MR. COVID-19 illness in native and immunosuppressed states: A clinical-therapeutic staging proposal. J Heart Lung Transplant. 2020 May;39(5):405-407. doi: 10.1016/j.healun.2020.03.012. Epub 2020 Mar 20. — View Citation

Van De Veerdonk FL, Netea MG, van Deuren M, van der Meer JWM, de Mast Q, Brüggemann RJ, van der Hoeven H. Kinins and cytokines in COVID-19: a comprehensive pathophysiological approach. 10.20944/preprints202004.0023.v1.

Yang G, Tan Z, Zhou L, Yang M, Peng L, Liu J, Cai J, Yang R, Han J, Huang Y, He S. Effects of Angiotensin II Receptor Blockers and ACE (Angiotensin-Converting Enzyme) Inhibitors on Virus Infection, Inflammatory Status, and Clinical Outcomes in Patients With COVID-19 and Hypertension: A Single-Center Retrospective Study. Hypertension. 2020 Jul;76(1):51-58. doi: 10.1161/HYPERTENSIONAHA.120.15143. Epub 2020 Apr 29. — View Citation

Zanichelli A, Maurer M, Aberer W, Caballero T, Longhurst HJ, Bouillet L, Fabien V, Andresen I; IOS Study Group. Long-term safety of icatibant treatment of patients with angioedema in real-world clinical practice. Allergy. 2017 Jun;72(6):994-998. doi: 10.1111/all.13103. Epub 2017 Mar 13. Erratum in: Allergy. 2018 Sep;73(9):1929. — View Citation

Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-1062. doi: 10.1016/S0140-6736(20)30566-3. Epub 2020 Mar 11. Erratum in: Lancet. 2020 Mar 28;395(10229):1038. Lancet. 2020 Mar 28;395(10229):1038. — View Citation

Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, Zhao X, Huang B, Shi W, Lu R, Niu P, Zhan F, Ma X, Wang D, Xu W, Wu G, Gao GF, Tan W; China Novel Coronavirus Investigating and Research Team. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020 Feb 20;382(8):727-733. doi: 10.1056/NEJMoa2001017. Epub 2020 Jan 24. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy of experimental treatment	Number of patients reaching grade 2 (inpatient, no longer requiring supplemental oxygen and no longer requiring care or grade 1 (hospital discharge) of the ordinal scale of the clinical state of the patient for 48 hours.	up to 10 days
Primary	Safety of experimental treatment	Number of patients without an adverse reaction scoring 3, 4 or 5 according to the Criteria of Adverse Event Terminology (CTC-AE).	up to 10 days
Secondary	Long-term efficacy	Number (percentage) of patients who reach grade 2 or grade 1 during the 10 days of to have initiated treatment.	up to 10 days
Secondary	Time to achive a clinical response	period time (days) between visit 1 (treatment start visit) and the day of gathering sustained 48-hour grade 2, grade 1 or grade 0 classification on the WHO 8-point ordinal scale for clinical status assessment The patient must be discharged from the hospital by the 28th day without a relapse or comorbidity related to COVID-19	up to 40 days
Secondary	Time to achive an afebrile state	period time (days) to reach a 48-hour sustained afebrile state (i.e., body temperature = 37.5ºC) without antipyretic medication.	up to 40 days
Secondary	time from symptom onset to treatment	period time (days) between the first COVID-19-related symptom and visit 1 (treatment start visit).	up to day 1
Secondary	Responders	Number (percentage) of patients considered as responders based on National Early Warning Score 2 (NEWS 2)	up to 40 days
Secondary	COVID-19 related relapse	number (and percentage) of patients discharged who presents any COVID-19-related relapse or comorbidity	up to 40 days
Secondary	Patients with Adverse Events	number of patients with Any Adverse Events	up to 40 days
Secondary	Adverse Events	Number of Adverse Events	up to 40 days
Secondary	Serious Adverse Events	Number of Serious Adverse Events	up to 40 days
Secondary	Overall mortality	number of patients who died	up to 40 days
Secondary	COVID-19 related mortality	number of patients who died due to COVID-19	up to 40 days
Secondary	Time until death	number of days from visit 1 until death	up to 40 days
Secondary	COVID-19-related complications	number of patients who had any COVID-19 related complications	up to 40 days
Secondary	Patients requiring intensive care	number of patients who require intensive care	up to 40 days
Secondary	patients requiring intensive care and invasive mechanical ventilation	number of patients who require intensive care and invasive mechanical ventilation	up to 40 days
Secondary	patients requiring oxygen supplementation	number of patients who require oxygen supplementation from hospital discharge up until visit 7	up to 40 days
Secondary	Patients with nonsocomial infection	number (and percentage) of patients diagnosed with another nosocomial infection	up to 40 days
Secondary	Rehospitalizations	number (and percentage) of patients who requires hospital readmission within 28 (± 3) days from hospital discharge	up to 40 days

External Links

•   COVID19, WHO
•   Icatibant (Firazyr®). Ficha técnica, Febrero 2019.