000153614 001__ 153614 000153614 005__ 20250508112647.0 000153614 0247_ $$2doi$$a10.31579/2690-4861/651 000153614 0248_ $$2sideral$$a143742 000153614 037__ $$aART-2025-143742 000153614 041__ $$aeng 000153614 100__ $$aJordán-Domingo, Marta 000153614 245__ $$aTreatment of Covid-19 Ambulatory Patients with A Medicinal Preparation of Echinacea Purpurea: The Ecco-2 Investigator-Initiated, Randomised, Double Blind, Controlled Trial 000153614 260__ $$c2025 000153614 5060_ $$aAccess copy available to the general public$$fUnrestricted 000153614 5203_ $$aBackground: The COVID-19 pandemic has affected millions throughout the entire world, causing an unprecedented disruption of the daily lives of many more millions. While vaccines have proven to be a powerful prophylactic tool co contain the spread of the disease, treatment options are very limited. Echinacea phytotherapy is known to be efficacious in the treatment of mild respiratory viral infections, therefore we and others hypothesized that it might be helpful in the treatment of ambulatory COVID-19. Purpose: To evaluate the clinical efficacy and safety of a medicinal preparation of cryo-milled root of Echinacea purpurea added to the standard-of-care (SOC) treatment in ambulatory COVID-19 patients with mild clinical symptoms, with a respiratory profile. Methods: We designed and conducted a prospective, double-blind, multicentre, randomized, controlled clinical trial involving four hospitals in Spain, from July 2021 to June 2022. Participants were ambulatory adults with COVID-19 infection, assessed by a positive PCR or antigen test, with mild symptoms of a respiratory profile. Patients were given Echinacea Arkopharma, hard caplets containing 250 mg of Echinacea purpurea (L.) Moench, 1.5 g/day (2 caplets every 8 hours, i.e., 6 g/day, 7 days) added to standard care (vide infra). Participants were followed for 28 additional days. The primary outcome of effectiveness (OE) was OE1: number of days with fever (body temperature ≥ 37ºC at any moment of the day). The secondary outcomes were OE2: days with subjective dyspnea, OE3: days with unsaturation (≤ 96%), OE4: days with disease, OE5: percentage of hospitalizations, OE6: length of hospitalization (days), OE7: days of sick leave, OE8: percentage to visits to emergency room, OE9: percentage of admissions to intensive care units, OE10: percentage of deaths, OE11: subjective perception by the recruiting physician of the treatment usefulness to improve the evolution of the disease, OE12: subjective perception by the patient of the treatment usefulness to improve the evolution of the disease. The secondary outcomes of safety (OS) were OS1: incidence of respiratory adverse effects, OS2: incidence of palpitations (> 110x'), OS3: incidence of transaminase elevations (AST level ≥ 3x the normal range limit), OS4: incidence of headaches, OS5: incidence of digestive adverse effects, OS6: incidence of insomnia and nervousness. For all cases, OS1 to OS6, percentage of dropouts for that specific reason. Results: The target recruitment number, 230, was not achieved. Rather, 99 eligible patients could be recruited (age 35.50 ± 11.9 years; 51.5 % female). They were randomised to SOC + treatment (n=50) and SOC + placebo group (n=49). There were no statistically significant differences between the treatment and placebo groups in the main variables studied, however, it should be noted that an important limitation of the study is the fact that we could not reach our recruitment target by far. Incidence of serious AEs was nil. Mild AE consisting of diarrhea were seen in 2 cases, and 1 effort- induced tachycardization, although there is no statistical evidence supporting that they were caused by the treatment. Conclusion: Echinacea, added to the SOC treatment for mild COVID-19, was safe and well tolerated but had no major impact on clinical outcomes. Some effectiveness trends suggest that further studies with full recruitment are warranted to definitively assess its efficacy in moderately affected COVID-19 patients. 000153614 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/ 000153614 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion 000153614 700__ $$aPrieto-Zapico, Azucena 000153614 700__ $$aRúa-Castro, Cristina 000153614 700__ $$aEito-Cuello, Juan 000153614 700__ $$aRequena, Jesús R. 000153614 700__ $$aCortés-Ayaso, María 000153614 700__ $$aEstany-Gestal, Ana 000153614 700__ $$0(orcid)0000-0001-8568-3098$$aSalvador-Oliván, José Antonio$$uUniversidad de Zaragoza 000153614 700__ $$aJiménez-Jara, Samuel 000153614 700__ $$0(orcid)0000-0001-6613-0359$$aAmores-Arriaga, Beatriz$$uUniversidad de Zaragoza 000153614 700__ $$aCabaleiro-Ocampo, Teresa 000153614 700__ $$aCostán-Galicia, Joaquín Carlos 000153614 700__ $$aVázquez-Torguet, Ana 000153614 700__ $$aMayán-Conesa, Plácido 000153614 700__ $$aSerrano-Godoy, Marcos 000153614 700__ $$aSarasquete-Fariña, Pablo 000153614 700__ $$aSánchez-Zapata, Mariña 000153614 700__ $$aVillena-Garcia del Real, Henrique 000153614 700__ $$aSempere-Serrano, Paloma 000153614 700__ $$aEspino-Paisán, Esther 000153614 700__ $$aMozo-Peñalver, Héctor 000153614 700__ $$aTari-Ferrer, Elvira 000153614 700__ $$0(orcid)0000-0002-9072-3768$$aNavarro-Aguilar, María Elena 000153614 700__ $$aContreras-Delgado, Karen Arlyn 000153614 700__ $$aSesam-Méndez, Cyntia 000153614 700__ $$aTorres-Peña, Isabel 000153614 700__ $$aPalacios-Aragonés, Ana 000153614 700__ $$aPardo-Jario, María del Puerto 000153614 700__ $$aFernández-Palomino, Alfonso 000153614 700__ $$aGriábal-García, Manuel 000153614 700__ $$aMorláns-Solanes, Claudia 000153614 700__ $$aCoiduras-Sanagustín, María Victoria 000153614 700__ $$aRuiz-Díaz, Loreto 000153614 700__ $$aCañardo-Alastuey, Inés 000153614 700__ $$aCasado-Pellejero, Ana 000153614 700__ $$aOrtega-Maján, María Teresa 000153614 700__ $$aMuniesa-Gracia, Paula 000153614 700__ $$aPérez-Pañart, Isabel 000153614 700__ $$aOrtiz-Bescós, Victoria 000153614 700__ $$aTutusaus-Arderiu, Cristina 000153614 700__ $$aOrdás-Arnal, Elena 000153614 700__ $$aRodríguez-Martínez, Sonia Beatriz 000153614 700__ $$aChapela-Castaño, María Teresa 000153614 700__ $$aGonzález-Losada, Sara 000153614 700__ $$aGonzález-Losada, Jésica 000153614 700__ $$aMaroño-Díaz, Ana María 000153614 700__ $$aCadórniga-Miranda, Daniel 000153614 700__ $$aMato-Vidal, María Eugenia 000153614 700__ $$aGómez-Lojo, Lidia 000153614 700__ $$aGonzález-Figueiras, Nuria 000153614 700__ $$aMoares-Castro, Verónica 000153614 700__ $$aMur Garcés, Ramón 000153614 700__ $$aPérez Polo, María Pilar 000153614 700__ $$aAlbiac, José Luis 000153614 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina 000153614 7102_ $$13011$$2040$$aUniversidad de Zaragoza$$bDpto. Ciencias Doc. Hª Ciencia$$cÁrea Biblioteconomía y Docum. 000153614 773__ $$g23, 1 (2025), 651 [8 pp.]$$pInt. j. clin. case rep. rev.$$tInternational Journal of Clinical Case Reports and Reviews$$x2690-4861 000153614 8564_ $$s559891$$uhttps://zaguan.unizar.es/record/153614/files/texto_completo.pdf$$yVersión publicada 000153614 8564_ $$s2786620$$uhttps://zaguan.unizar.es/record/153614/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada 000153614 909CO $$ooai:zaguan.unizar.es:153614$$particulos$$pdriver 000153614 951__ $$a2025-05-08-09:45:16 000153614 980__ $$aARTICLE