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Early intervention with azelastine nasal spray may reduce viral load in SARS-CoV-2 infected patients

Klussmann et al., Scientific Reports, doi:10.1038/s41598-023-32546-z, CARVIN
Apr 2023  
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Recovery, 0.1% 13% Improvement Relative Risk Recovery, 0.02% -33% Recovery, 0.1% (b) 66% Recovery, 0.02% (b) 67% Viral load, 0.1% 14% Viral load, 0.02% 7% Viral clearance, AUC, 0.1% 22% Viral clearance, AUC, 0.02% 6% Azelastine  CARVIN  EARLY TREATMENT  DB RCT Is early treatment with azelastine beneficial for COVID-19? Double-blind RCT 61 patients in Germany Improved recovery (p=0.54) and viral clearance (p=0.22), not sig. c19early.org Klussmann et al., Scientific Reports, Apr 2023 Favorsazelastine Favorscontrol 0 0.5 1 1.5 2+
RCT 90 outpatients showing potential benefit of azelastine nasal spray for reducing viral load. Patients were randomized to receive placebo, 0.02%, or 0.1% azelastine nasal spray for 11 days. The 0.1% azelastine group showed greater viral load reduction compared to placebo (p=0.007) and achieved PCR negativity earlier (48.2% vs 23.1% negative by day 11). Symptoms improved across all groups, with the 0.1% group showing slightly greater improvement (12.74 point reduction vs 11.12 for placebo) and significantly better improvement in shortness of breath on days 3-4. No significant differences were found in quality of life measures or WHO clinical progression scores.
risk of no recovery, 12.7% lower, RR 0.87, p = 0.54, treatment mean 12.74 (±10.74) n=29, control mean 11.12 (±9.45) n=30, 0.1%.
risk of no recovery, 32.7% higher, RR 1.33, p = 0.26, treatment mean 8.38 (±9.42) n=31, control mean 11.12 (±9.45) n=30, 0.02%.
risk of no recovery, 66.3% lower, RR 0.34, p = 1.00, treatment 0 of 29 (0.0%), control 1 of 30 (3.3%), NNT 30, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), 0.1%.
risk of no recovery, 67.0% lower, RR 0.33, p = 0.49, treatment 0 of 31 (0.0%), control 1 of 30 (3.3%), NNT 30, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), 0.02%.
viral load, 14.2% lower, relative load 0.86, p = 0.22, treatment mean 4.45 (±2.25) n=29, control mean 3.82 (±1.61) n=30, 0.1%.
viral load, 7.3% lower, relative load 0.93, p = 0.52, treatment mean 4.12 (±2.01) n=31, control mean 3.82 (±1.61) n=30, 0.02%.
risk of no viral clearance, 21.7% lower, RR 0.78, p = 0.04, treatment mean 24.14 (±13.12) n=29, control mean 18.89 (±4.7) n=30, relative AUC, 0.1%.
risk of no viral clearance, 6.2% lower, RR 0.94, p = 0.54, treatment mean 24.14 (±12.56) n=31, control mean 22.64 (±4.7) n=30, relative AUC, 0.02%.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Klussmann et al., 26 Apr 2023, Double Blind Randomized Controlled Trial, placebo-controlled, Germany, peer-reviewed, 27 authors, CARVIN trial. Contact: ralph@moesges.de.
This PaperMiscellaneousAll
Early intervention with azelastine nasal spray may reduce viral load in SARS-CoV-2 infected patients
Jens Peter Klussmann, Maria Grosheva, Peter Meiser, Clara Lehmann, Eszter Nagy, Valéria Szijártó, Gábor Nagy, Robert Konrat, Michael Flegel, Frank Holzer, Dorothea Groß, Charlotte Steinmetz, Barbara Scherer, Henning Gruell, Maike Schlotz, Florian Klein, Paula Aguiar De Aragão, Henning Morr, Helal Al Saleh, Andreas Bilstein, Belisa Russo, Susanne Müller-Scholtz, Cengizhan Acikel, Hacer Sahin, Nina Werkhäuser, Silke Allekotte, Ralph Mösges
Scientific Reports, doi:10.1038/s41598-023-32546-z
With the changing epidemiology of COVID-19 and its impact on our daily lives, there is still an unmet need of COVID-19 therapies treating early infections to prevent progression. The current study was a randomized, parallel, double-blind, placebo-controlled trial. Ninety SARS-CoV-2 positive patients were randomized into 3 groups receiving placebo, 0.02% or 0.1% azelastine nasal spray for 11 days, during which viral loads were assessed by quantitative PCR. Investigators assessed patients' status throughout the trial including safety follow-ups (days 16 and 60). Symptoms were documented in patient diaries. Initial viral loads were log 10 6.85 ± 1.31 (mean ± SD) copies/mL (ORF 1a/b gene). After treatment, virus load was reduced in all groups (p < 0.0001) but was greater in the 0.1% group compared to placebo (p = 0.007). In a subset of patients (initial Ct < 25) viral load was strongly reduced on day 4 in the 0.1% group compared to placebo (p = 0.005). Negative PCR results appeared earlier and more frequently in the azelastine treated groups: being 18.52% and 21.43% in the 0.1% and 0.02% groups, respectively, compared to 0% for placebo on day 8. Comparable numbers of adverse events occurred in all treatment groups with no safety concerns. The shown effects of azelastine nasal spray may thus be suggestive of azelastine's potential as an antiviral treatment. Trial registration: The study was registered in the German Clinical Trial Register (DRKS-ID: DRKS00024520; Date of Registration in DRKS: 12/02/2021). EudraCT number: 2020-005544-34. Since viral levels during early infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) tend to be highest in the nose and nasopharynx 1 , a nasal spray with an active substance inhibiting virus entry and replication may stop or delay the progression of the disease to the lower respiratory system and reduce the transmission to uninfected individuals. Azelastine hydrochloride nasal spray is an approved medicinal product currently available at a concentration of 0.1% w/v to treat allergic rhinitis. The active substance (azelastine hydrochloride) is a histamine-1 receptor antagonist, which shows anti-inflammatory effects via mast cell stabilization and inhibition of leukotriene and pro-inflammatory cytokine production 2-4 .
Ethics declarations. Ethics approval was granted by the Ethics Committee of the Faculty of Medicine of Author contributions J.P.K. was the principal investigator responsible for the conduct of the study, M.G. was the deputy investigator. C.L. was responsible for the patient disposition. E.N., V.S., G.N., R.K., A.B., M.F. and F.H. contributed to the study conceptualisation. R.M., S.M.S., S.A. and P.M. designed the study protocol. P.A.de.A., H.M. and H.A.S. were investigators involved in the conduct of the study. H.G., M.S., and F.K. performed and supervised sample processing and viral load measurements. D.G., C.S. and B.S. were involved in data management. B.R. drafted the manuscript. H.S. was responsible for data management activities. C.A. performed the statistical analysis. N.W. reviewed, edited and finalised the manuscript. All authors contributed to the preparation of the manuscript, read and approved the manuscript. Competing interests JPK and CL have received grants from the sponsor URSAPHARM Arzneimittel GmbH for performing this trial. EN, VS and GN are shareholders in CEBINA GmbH, RK and EN are inventors on related patent applications. PM, MF, DG, CS and BS are employed at URSAPHARM Arzneimittel GmbH. FH is the CEO of URSAPHARM Arzneimittel GmbH. BR, SMS, HS, CA, NW, SA, and RM are employees of ClinCompetence Cologne, the CRO which organized this trial. HG, MS, and FK declare no conflict of interest. MG, PA, HM and HAS declare no conflict of interest. AB is..
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' 'https://doi.org/10.3390/pharmaceutics14102059 (2022).', 'journal-title': 'Pharmaceutics'}], 'container-title': 'Scientific Reports', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://www.nature.com/articles/s41598-023-32546-z.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://www.nature.com/articles/s41598-023-32546-z', 'content-type': 'text/html', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://www.nature.com/articles/s41598-023-32546-z.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2023, 4, 26]], 'date-time': '2023-04-26T13:10:34Z', 'timestamp': 1682514634000}, 'score': 1, 'resource': {'primary': {'URL': 'https://www.nature.com/articles/s41598-023-32546-z'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2023, 4, 26]]}, 'references-count': 35, 'journal-issue': {'issue': '1', 'published-online': {'date-parts': [[2023, 12]]}}, 'alternative-id': ['32546'], 'URL': 'http://dx.doi.org/10.1038/s41598-023-32546-z', 'relation': {}, 'ISSN': ['2045-2322'], 'subject': ['Multidisciplinary'], 'container-title-short': 'Sci Rep', 'published': {'date-parts': [[2023, 4, 26]]}, 'assertion': [ { 'value': '25 July 2022', 'order': 1, 'name': 'received', 'label': 'Received', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '29 March 2023', 'order': 2, 'name': 'accepted', 'label': 'Accepted', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '26 April 2023', 'order': 3, 'name': 'first_online', 'label': 'First Online', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': 'JPK and CL have received grants from the sponsor URSAPHARM Arzneimittel GmbH ' 'for performing this trial. EN, VS and GN are shareholders in CEBINA GmbH, RK ' 'and EN are inventors on related patent applications. PM, MF, DG, CS and BS are ' 'employed at URSAPHARM Arzneimittel GmbH. FH is the CEO of URSAPHARM ' 'Arzneimittel GmbH. BR, SMS, HS, CA, NW, SA, and RM are employees of ' 'ClinCompetence Cologne, the CRO which organized this trial. HG, MS, and FK ' 'declare no conflict of interest. MG, PA, HM and HAS declare no conflict of ' 'interest. AB is employed at Ursatec GmbH, supplier of primary packing materials ' 'to Ursapharm.', 'order': 1, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Competing interests'}}], 'article-number': '6839'}
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. FLCCC and WCH provide treatment protocols.
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