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

Malchair et al., Clinical Infectious Diseases, doi:10.1093/cid/ciac984, ICAT•COVID, NCT04978051, Jan 2023

https://c19early.org/malchair.html

RCT 77 hospitalized COVID-19 pneumonia patients requiring supplemental oxygen, showing reduced oxygen requirements, hospital stay, and mortality with icatibant treatment compared to standard care alone.

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risk of death, 47.0% lower, HR 0.53, p = 0.01, treatment 37, control 36, Bayesian, Kaplan–Meier.

risk of no hospital discharge, 46.0% lower, HR 0.54, p = 0.01, treatment 37, control 36, Kaplan–Meier.

risk of oxygen therapy, 41.0% lower, HR 0.59, p = 0.03, treatment 37, control 36, Kaplan–Meier.

Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates

Malchair et al., 4 Jan 2023, Randomized Controlled Trial, Spain, peer-reviewed, 18 authors, study period April 2021 - February 2022, trial NCT04978051 (history) (ICAT•COVID).

This Paper Icatibant All

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

Pierre Malchair, Jordi Giol, Vanesa García, Orlando Rodríguez, José Carlos Ruibal, Alvaro Zarauza, Ferrán Llopis, Leire Matellán, Tania Bernal, Beatriz Solís, Aurema Otero, Thiago Carnaval, Hector Jofre, Javier Jacob, Xavier Solanich, Arnau Antolí, Gemma Rocamora, Sebastián Videla

Clinical Infectious Diseases, doi:10.1093/cid/ciac984

Background. We aimed to evaluate icatibant, a competitive antagonist of the bradykinin B2 receptors, for the treatment of inpatients with coronavirus disease 2019 (COVID-19) pneumonia admitted in the early hypoxemic stage. Methods. The randomized, open-label clinical trial of icatibant for COVID-19 pneumonia (ICAT•COVID, registered as NCT04978051 at ClinicalTrials.gov) was conducted in Barcelona. Inpatients requiring supplemental but not high-flow oxygen or mechanical ventilation were allocated (1:1) to treatment with either three 30-mg icatibant doses/d for 3 consecutive days plus standard care or standard care alone, and followed for up to 28 days after initial discharge. The primary and key secondary outcomes were clinical response on study day 10/discharge and clinical efficacy at 28 days from initial discharge, respectively. Results. Clinical response occurred in 27 of 37 patients (73.0%) in the icatibant group and 20 of 36 patients (55.6%) in the control group (rate difference, 17.42; 95% confidence interval [CI], -4.22 to 39.06; P = .115). Clinical efficacy ensued in 37 patients (100.0%) in the icatibant group and 30 patients (83.3%) in the control group (rate difference, 16.67; 95% CI, 4.49-28.84; P = .011). No patient died in the icatibant group, compared with 6 patients (16.7%) in the control group (P = .011). All patients but 1 had adverse events, which were evenly distributed between study arms. No patient withdrew because of adverse events. Conclusions. Adding icatibant to standard care was safe and improved both COVID-19 pneumonia and mortality in this proofof-concept study. A larger, phase 3 trial is warranted to establish the clinical value of this treatment. Clinical Trials Registration. NCT04978051.

this information will be evaluated on a case-by-case basis, on reasonable request by the interested party, and with permission from Pierre Malchair, the coordinator of this study. Data access requests should be addressed to Pierre Malchair at pierre.malchair@bellvitgehospital.cat. Financial support. This collaborative research clinical trial received funding and the experimental drug product (icatibant) from Takeda Farmacéutica España. Funding from Takeda was for expenses related to administrative procedures for clinical trial startup, fees of the institutional review board and from the AEMPS (Spain's Regulatory Authority), as well as for the Contract Research Organization engaged to carry out study monitoring, the pharmacovigilance, the e-Case Report Form (CRF) preparation and statistical analysis, and the final report. Takeda, the marketing authorization holder of icatibant contributed with the experimental study product, valued at over one million euros. Potential conflicts of interest. Alonso Fernández, Ana Sánchez-Gabriel, Carmen Montoto, and Marta Benjumeda have full-time positions at Takeda Farmacéutica España. All authors report provision of the study medication, unrelated to this work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

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DOI record: { "DOI": "10.1093/cid/ciac984", "ISSN": [ "1058-4838", "1537-6591" ], "URL": "http://dx.doi.org/10.1093/cid/ciac984", "abstract": "Abstract\n \n Background\n We aimed to evaluate icatibant, a competitive antagonist of the bradykinin B2 receptors, for the treatment of inpatients with coronavirus disease 2019 (COVID-19) pneumonia admitted in the early hypoxemic stage.\n \n \n Methods\n The randomized, open-label clinical trial of icatibant for COVID-19 pneumonia (ICAT·COVID, registered as NCT04978051 at ClinicalTrials.gov) was conducted in Barcelona. Inpatients requiring supplemental but not high-flow oxygen or mechanical ventilation were allocated (1:1) to treatment with either three 30-mg icatibant doses/d for 3 consecutive days plus standard care or standard care alone, and followed for up to 28 days after initial discharge. The primary and key secondary outcomes were clinical response on study day 10/discharge and clinical efficacy at 28 days from initial discharge, respectively.\n \n \n Results\n Clinical response occurred in 27 of 37 patients (73.0%) in the icatibant group and 20 of 36 patients (55.6%) in the control group (rate difference, 17.42; 95% confidence interval [CI], −4.22 to 39.06; P = .115). Clinical efficacy ensued in 37 patients (100.0%) in the icatibant group and 30 patients (83.3%) in the control group (rate difference, 16.67; 95% CI, 4.49-28.84; P = .011). No patient died in the icatibant group, compared with 6 patients (16.7%) in the control group (P = .011). All patients but 1 had adverse events, which were evenly distributed between study arms. No patient withdrew because of adverse events.\n \n \n Conclusions\n Adding icatibant to standard care was safe and improved both COVID-19 pneumonia and mortality in this proof-of-concept study. 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"Beigel", "doi-asserted-by": "crossref", "first-page": "1813", "journal-title": "N Engl J Med", "key": "2023053019073166500_ciac984-B25", "volume": "383", "year": "2020" }, { "DOI": "10.1155/2022/7423537", "article-title": "Dysregulated bradykinin: mystery in the pathogenesis of COVID-19", "author": "Tabassum", "doi-asserted-by": "crossref", "journal-title": "Mediators Inflamm", "key": "2023053019073166500_ciac984-B26", "volume": "2022", "year": "2022" }, { "DOI": "10.34172/jrip.2020.19", "article-title": "COVID-19 interactions with angiotensin-converting enzyme 2 (ACE2) and the kinin system; looking at a potential treatment", "author": "Tolouian", "doi-asserted-by": "crossref", "first-page": "e19", "journal-title": "J Renal Inj Prev", "key": "2023053019073166500_ciac984-B27", "volume": "9", "year": "2020" }, { "article-title": "Treatment potential and cost projection regarding use of icatibant or lanadelumab for therapy of COVID-19 associated respiratory distress syndrome", "author": "Osmic", "first-page": "1613", "journal-title": "Br J Clin Pharmacol", "key": "2023053019073166500_ciac984-B28", "volume": "87", "year": "2021" } ], "reference-count": 28, "references-count": 28, "relation": {}, "resource": { "primary": { "URL": "https://academic.oup.com/cid/article/76/10/1784/6969085" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [], "subtitle": [], "title": "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", "type": "journal-article", "volume": "76" }

Late treatment
is less effective

Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. IMA and WCH provide treatment protocols.

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