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

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.

Timeline

Start

2021-04-12

Primary completion

2021-11-30

Completion

2022-03-17

Outcome

Missed primary endpoint

paper rate difference, 17.42; 95% confidence interval [CI], -4.22 to 39.06; P = .115 PMID 36610464 ↗

Publications

• Background 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.
• Background Busse PJ, Christiansen SC. Hereditary Angioedema. N Engl J Med. 2020 Mar 19;382(12):1136-1148. doi: 10.1056/NEJMra1808012. No abstract available.
• Background 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.
• Background Cicardi M, Banerji A, Bracho F, Malbran 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, Anne S, Bjorkander J, Bouillet L, Cillari E, Hurewitz D, Jacobson KW, Katelaris CH, Maurer M, Merk H, Bernstein JA, Feighery C, Floccard B, Gleich G, Hebert J, Kaatz M, Keith P, Kirkpatrick CH, Langton D, Martin L, Pichler C, Resnick D, Wombolt D, Fernandez 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.
• Background Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31-41. doi: 10.1159/000180580.
• Background 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.
• Background 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.
• Background 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.
• Background 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. No abstract available.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Malchair P, Giol J, Garcia V, Rodriguez O, Ruibal JC, Zarauza A, Llopis F, Matellan L, Bernal T, Solis B, Otero A, Carnaval T, Jofre H, Jacob J, Solanich X, Antoli A, Rocamora G, Videla S. Three-Day Icatibant on Top of Standard Care in Patients With Coronavirus Disease 2019 Pneumonia: A Randomized, Open-Label, Phase 2, Proof-of-Concept Trial. Clin Infect Dis. 2023 May 24;76(10):1784-1792. doi: 10.1093/cid/ciac984.
• Malchair P, Otero A, Giol J, Solanich X, Carnaval T, Fernandez-Nistal A, Sanchez-Gabriel A, Montoto C, Lleonart R, Videla S; ICAT-COVID team. A multicenter, open-label, randomized, proof-of-concept phase II clinical trial to assess the efficacy and safety of icatibant in patients infected with SARS-CoV-2 (COVID-19) and admitted to hospital units without invasive mechanical ventilation: study protocol (ICAT-COVID). Trials. 2022 Apr 12;23(1):303. doi: 10.1186/s13063-022-06219-7.

Drugs

Indications