Analgesics
Antiandrogens
Azvudine
Bromhexine
Budesonide
Colchicine
Conv. Plasma
Curcumin
Famotidine
Favipiravir
Fluvoxamine
Hydroxychlor..
Ivermectin
Lifestyle
Melatonin
Metformin
Minerals
Molnupiravir
Monoclonals
Naso/orophar..
Nigella Sativa
Nitazoxanide
Paxlovid
Quercetin
Remdesivir
Thermotherapy
Vitamins
More

Other
Feedback
Home
Top
Results
Abstract
All nitric oxide studies
Meta analysis
 
Feedback
Home
next
study
previous
study
c19early.org COVID-19 treatment researchNitric OxideNitric Oxide (more..)
Melatonin Meta
Metformin Meta
Azvudine Meta
Bromhexine Meta Molnupiravir Meta
Budesonide Meta
Colchicine Meta
Conv. Plasma Meta Nigella Sativa Meta
Curcumin Meta Nitazoxanide Meta
Famotidine Meta Paxlovid Meta
Favipiravir Meta Quercetin Meta
Fluvoxamine Meta Remdesivir Meta
Hydroxychlor.. Meta Thermotherapy Meta
Ivermectin Meta

All Studies   Meta Analysis    Recent:   

SARS-CoV-2 accelerated clearance using a novel nitric oxide nasal spray (NONS) treatment: A randomized trial

Tandon et al., The Lancet Regional Health - Southeast Asia, doi:10.1016/j.lansea.2022.100036, CTRI/2021/08
Jun 2022  
  Post
  Facebook
Share
  Source   PDF   All Studies   Meta AnalysisMeta
Improvement, mITT-HR.. 68% Improvement Relative Risk Improvement, mITT-.. (b) 67% Improvement, mITT.. (c) 42% Improvement, mITT, day 18 22% Improvement, mITT, day 16 18% Improvement, mITT, day 8 9% Viral load, mITT-HR 20% Viral load, mITT 14% Time to viral-, mITT-HR 26% Time to viral-, mITT 6% Nitric Oxide  Tandon et al.  EARLY TREATMENT  DB RCT Is early treatment with nitric oxide beneficial for COVID-19? Double-blind RCT 207 patients in India (August 2021 - January 2022) Improved viral clearance with nitric oxide (p<0.000001) c19early.org Tandon et al., The Lancet Regional Hea.., Jun 2022 Favorsnitric oxide Favorscontrol 0 0.5 1 1.5 2+
RCT with 153 patients treated with a nitric oxide nasal spray, and 153 placebo patients, showing faster viral clearance with treatment. NO generated by a nasal spray (NONS) self-administered six times daily as two sprays per nostril (0.45mL of solution/dose) for seven days.
Targeted administration to the respiratory tract provides treatment directly to the typical source of initial SARS-CoV-2 infection and replication, and allows for rapid onset of action, higher local drug concentration, and reduced systemic side effects.
risk of no improvement, 67.7% lower, RR 0.32, p = 0.08, treatment 3 of 64 (4.7%), control 10 of 69 (14.5%), NNT 10, mITT high risk, day 18.
risk of no improvement, 66.8% lower, RR 0.33, p = 0.04, treatment 4 of 64 (6.2%), control 13 of 69 (18.8%), NNT 7.9, mITT high risk, day 16.
risk of no improvement, 41.9% lower, RR 0.58, p = 0.06, treatment 14 of 64 (21.9%), control 26 of 69 (37.7%), NNT 6.3, mITT high risk, day 8.
risk of no improvement, 22.3% lower, RR 0.78, p = 0.63, treatment 8 of 105 (7.6%), control 10 of 102 (9.8%), NNT 46, day 18, modified intention-to-treat.
risk of no improvement, 17.8% lower, RR 0.82, p = 0.67, treatment 11 of 105 (10.5%), control 13 of 102 (12.7%), NNT 44, day 16, modified intention-to-treat.
risk of no improvement, 8.9% lower, RR 0.91, p = 0.76, treatment 30 of 105 (28.6%), control 32 of 102 (31.4%), NNT 36, day 8, modified intention-to-treat.
viral load, 19.8% lower, relative load 0.80, p < 0.001, treatment mean 2.62 (±0.145) n=64, control mean 2.1 (±0.141) n=69, mITT high risk, day 8.
viral load, 13.5% lower, relative load 0.86, p < 0.001, treatment mean 2.51 (±0.114) n=105, control mean 2.17 (±0.118) n=102, day 8, modified intention-to-treat.
time to viral-, 26.1% lower, relative time 0.74, p = 0.09, treatment 64, control 69, inverted to make RR<1 favor treatment, mITT high risk, Kaplan–Meier.
time to viral-, 6.5% lower, relative time 0.94, p = 0.66, treatment 105, control 102, inverted to make RR<1 favor treatment, Kaplan–Meier, modified intention-to-treat.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Tandon et al., 29 Jun 2022, Double Blind Randomized Controlled Trial, placebo-controlled, India, peer-reviewed, 10 authors, study period 10 August, 2021 - 25 January, 2022, trial CTRI/2021/08. Contact: monika.tandon@glenmarkpharma.com.
This PaperNitric OxideAll
SARS-CoV-2 accelerated clearance using a novel nitric oxide nasal spray (NONS) treatment: A randomized trial
Monika Tandon, Wen Wu, Keith Moore, Stephen Winchester, Yuan-Po Tu, Christopher Miller, Rahul Kodgule, Amol Pendse, Shabbir Rangwala, Shashank Joshi
The Lancet Regional Health - Southeast Asia, doi:10.1016/j.lansea.2022.100036
Background Additional outpatient therapies which are readily accessible will be essential to reduce COVID-19 illness progression in high risk individuals. Especially as the virus continues to mutate with greater transmissibility despite increased global vaccination. Methods A randomized, double-blind, multicentre, parallel group, placebo-controlled phase III clinical trial evaluated the ability of nitric oxide (NO) to rapidly eradicate nasal SARS-CoV-2 RNA. Adults (18À70 years) with mild symptomatic COVID-19 were randomized, confirmed by laboratory SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) nasal swab. Randomisation was 1:1, NONS (N = 153) vs placebo (N = 153). NO generated by a nasal spray (NONS) was self-administered six times daily as two sprays per nostril (0Á45 mL of solution/dose) for seven days. Patients at high risk of illness progression, defined as unvaccinated, 45 years of age or having comorbidities, were the primary analysis population. Findings Overall, mean SARS-CoV-2 RNA concentrations (6¢96 log10 copies/mL in the NONS group and 7¢16 log10 copies/mL in the placebo group) were comparable at baseline. Primary endpoint mean treatment difference SARS-CoV-2 RNA change from baseline to the end of treatment (EOT) was -0¢52 copies/mL (SE 0¢202, 95% CI -0¢ 92 to -0¢12; p = 0¢010) with NONS compared to placebo. Secondary endpoint assessments demonstrated a greater proportion of patients receiving NONS (82¢8%) cleared SARS-CoV-2 (RT-PCR negative) by EOT compared to placebo (66¢7%, p = 0¢046), with no virus RNA detected a median of four days earlier compared to placebo (three vs seven days; p = 0¢044). Interpretation Use of NONS in patients recently infected with SARS-CoV-2 accelerates nasal virus clearance.
Supplementary materials Supplementary material associated with this article can be found in the online version at doi:10.1016/j.lan sea.2022.100036.
References
Akaberi, Krambrich, Ling, Mitigation of the replication of SARS-CoV-2 by nitric oxide in vitro, Redox Biol, doi:10.1016/j.redox.2020.101734
Fang, Perspectives series: host/pathogen interactions. Mechanisms of nitric oxide-related antimicrobial activity, J Clin Invest
Friedland, Tucker, Goodall, In vivo (human) and in vitro inactivation of SARS-CoV-2 with 0.5% povidone-iodine nasal spray, Aust J Otolaryng, doi:10.21037/ajo-21-40
Giarratana, Rajan, Kamala, Mendenhall, Giorgio, A sprayable Acid-Oxidizing solution containing hypochlorous acid (AOS2020) efficiently and safely inactivates SARS-Cov-2: a new potential solution for upper respiratory tract hygiene, Eur Archi Oto-Rhino-Laryngology, doi:10.1007/s00405-021-06644-5
Hirabara, Serdan, Gorjao, SARS-COV-2 variants: differences and potential of immune evasion, Front Cell Infect Microbiol, doi:10.3389/fcimb.2021.781429
Jin, Yang, Virology, epidemiology, pathogenesis, and control of COVID-19, Viruses, doi:10.3390/v12040372
Kerstr€ Om S, Gunalan, Keng, Tan, Mirazimi, Dual effect of nitric oxide on SARS-CoV replication: viral RNA production and palmitoylation of the S protein are affected, Virology
Lisi, Zelikin, Chandrawati, Nitric oxide to fight viral infections, Adv Sci, doi:10.1002/advs.202003895
Mccarthy, Rennick, Nambulli, Recurrent deletions in the SARS-CoV-2 spike glycoprotein drive antibody escape, Science
Moncada, Higgs, Endogenous nitric oxide: physiology, pathology, and clinical relevance, Eur J Clin Invest
Motozono, Toyoda, Zahradnik, SARS-CoV-2 spike L452R variant evades cellular immunity and increases infectivity, Cell Host Microbe, doi:10.1016/j.chom.2021.06.006
Pajon, Paila, Girard, Initial analysis of viral dynamics and circulating viral variants during the mRNA-1273 Phase 3 COVE trial, Nat Med, doi:10.1038/s41591-022-01679-5
Regev-Shoshani, Vimalanathan, Mcmullin, Road, Gay et al., Gaseous nitric oxide reduces influenza infectivity in vitro, Nitric Oxide
Weinreich, Sivapalasingam, Norton, REGEN-COV antibody combination and outcomes in outpatients with COVID-19, N Engl J Med, doi:10.1056/NEJMoa2108163
Winchester, John, Jabbar, Isaac, Clinical efficacy of nitric oxide nasal spray (NONS) for the treatment of mild COVID-19 infection, J Infect, doi:10.1016/j.jinf.2021.05.009
Yeh, Using trapezoidal rule for the area under a curve calculation
Yu, Sun, Shi, Wang, Zhao et al., SARSCoV-2 viral load in sputum correlates with risk of COVID-19 progression, Crit Care, doi:10.1186/s13054-020-02893-8
Zou, Ruan, Huang, Liang, Huang et al., SARS-CoV-2 viral load in upper respiratory specimens of infected patients, N Engl J Med
{ 'indexed': {'date-parts': [[2022, 7, 13]], 'date-time': '2022-07-13T06:41:44Z', 'timestamp': 1657694504651}, 'reference-count': 25, 'publisher': 'Elsevier BV', 'license': [ { 'start': { 'date-parts': [[2022, 6, 1]], 'date-time': '2022-06-01T00:00:00Z', 'timestamp': 1654041600000}, 'content-version': 'tdm', 'delay-in-days': 0, 'URL': 'https://www.elsevier.com/tdm/userlicense/1.0/'}, { 'start': { 'date-parts': [[2022, 6, 25]], 'date-time': '2022-06-25T00:00:00Z', 'timestamp': 1656115200000}, 'content-version': 'vor', 'delay-in-days': 24, 'URL': 'http://creativecommons.org/licenses/by/4.0/'}], 'content-domain': {'domain': [], 'crossmark-restriction': False}, 'published-print': {'date-parts': [[2022, 6]]}, 'DOI': '10.1016/j.lansea.2022.100036', 'type': 'journal-article', 'created': {'date-parts': [[2022, 6, 29]], 'date-time': '2022-06-29T06:31:35Z', 'timestamp': 1656484295000}, 'page': '100036', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'SARS-CoV-2 accelerated clearance using a novel nitric oxide nasal spray (NONS) treatment: A ' 'randomized trial', 'prefix': '10.1016', 'author': [ {'given': 'Monika', 'family': 'Tandon', 'sequence': 'first', 'affiliation': []}, {'given': 'Wen', 'family': 'Wu', 'sequence': 'additional', 'affiliation': []}, {'given': 'Keith', 'family': 'Moore', 'sequence': 'additional', 'affiliation': []}, {'given': 'Stephen', 'family': 'Winchester', 'sequence': 'additional', 'affiliation': []}, {'given': 'Yuan-Po', 'family': 'Tu', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-5697-2779', 'authenticated-orcid': False, 'given': 'Christopher', 'family': 'Miller', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0003-1701-2115', 'authenticated-orcid': False, 'given': 'Rahul', 'family': 'Kodgule', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0001-6333-7098', 'authenticated-orcid': False, 'given': 'Amol', 'family': 'Pendse', 'sequence': 'additional', 'affiliation': []}, {'given': 'Shabbir', 'family': 'Rangwala', 'sequence': 'additional', 'affiliation': []}, {'given': 'Shashank', 'family': 'Joshi', 'sequence': 'additional', 'affiliation': []}], 'member': '78', 'reference': [ { 'key': '10.1016/j.lansea.2022.100036_bib0001', 'unstructured': 'World Health Organization. Coronavirus (COVID-19) Dashboard. ' 'https://covid19.who.int/. Accessed 1 March 2022'}, { 'issue': '2', 'key': '10.1016/j.lansea.2022.100036_bib0002', 'doi-asserted-by': 'crossref', 'first-page': '237', 'DOI': '10.1016/j.jinf.2021.05.009', 'article-title': 'Clinical efficacy of nitric oxide nasal spray (NONS) for the treatment ' 'of mild COVID-19 infection', 'volume': '83', 'author': 'Winchester', 'year': '2021', 'journal-title': 'J Infect'}, { 'key': '10.1016/j.lansea.2022.100036_bib0003', 'doi-asserted-by': 'crossref', 'DOI': '10.1016/j.redox.2020.101734', 'article-title': 'Mitigation of the replication of SARS-CoV-2 by nitric oxide in vitro', 'volume': '37', 'author': 'Akaberi', 'year': '2020', 'journal-title': 'Redox Biol'}, { 'issue': '4', 'key': '10.1016/j.lansea.2022.100036_bib0004', 'doi-asserted-by': 'crossref', 'first-page': '361', 'DOI': '10.1111/j.1365-2362.1991.tb01383.x', 'article-title': 'Endogenous nitric oxide: physiology, pathology, and clinical relevance', 'volume': '21', 'author': 'Moncada', 'year': '1991', 'journal-title': 'Eur J Clin Invest'}, { 'issue': '12', 'key': '10.1016/j.lansea.2022.100036_bib0005', 'doi-asserted-by': 'crossref', 'first-page': '2818', 'DOI': '10.1172/JCI119473', 'article-title': 'Perspectives series: host/pathogen interactions. Mechanisms of nitric ' 'oxide-related antimicrobial activity', 'volume': '99', 'author': 'Fang', 'year': '1997', 'journal-title': 'J Clin Invest'}, { 'key': '10.1016/j.lansea.2022.100036_bib0006', 'doi-asserted-by': 'crossref', 'first-page': '48', 'DOI': '10.1016/j.niox.2013.03.007', 'article-title': 'Gaseous nitric oxide reduces influenza infectivity in vitro', 'volume': '31', 'author': 'Regev-Shoshani', 'year': '2013', 'journal-title': 'Nitric Oxide'}, { 'issue': '1', 'key': '10.1016/j.lansea.2022.100036_bib0007', 'doi-asserted-by': 'crossref', 'first-page': '1', 'DOI': '10.1016/j.virol.2009.09.007', 'article-title': 'Dual effect of nitric oxide on SARS-CoV replication: viral RNA ' 'production and palmitoylation of the S protein are affected', 'volume': '395', 'author': 'Åkerström', 'year': '2009', 'journal-title': 'Virology'}, { 'key': '10.1016/j.lansea.2022.100036_bib0008', 'series-title': 'Assessing COVID-19-Related Symptoms in Outpatient Adult and Adolescent ' 'Subjects in Clinical Trials of Drugs and Biological Products for ' 'COVID-19 Prevention or Treatment Guidance for Industry', 'year': '2020'}, { 'key': '10.1016/j.lansea.2022.100036_bib0009', 'doi-asserted-by': 'crossref', 'first-page': 'e192', 'DOI': '10.1016/S1473-3099(20)30483-7', 'article-title': 'A minimal common outcome measure set for COVID-19 clinical research', 'volume': '20', 'year': '2020', 'journal-title': 'Lancet Infect Dis'}, { 'key': '10.1016/j.lansea.2022.100036_bib0010', 'unstructured': 'Yeh S Using trapezoidal rule for the area under a curve calculation. SAS ' 'Conference Proceedings: SAS User Group International Conference (SUGI) ' '-27, 2002, Paper ' '229-27.https://support.sas.com/resources/papers/proceedings/proceedings/sugi27/p229-27.pdf. ' 'Accessed 21 May 2021.'}, { 'key': '10.1016/j.lansea.2022.100036_bib0011', 'doi-asserted-by': 'crossref', 'first-page': '823', 'DOI': '10.1038/s41591-022-01679-5', 'article-title': 'Initial analysis of viral dynamics and circulating viral variants ' 'during the mRNA-1273 Phase 3 COVE trial', 'volume': '28', 'author': 'Pajon', 'year': '2022', 'journal-title': 'Nat Med'}, { 'key': '10.1016/j.lansea.2022.100036_bib0012', 'doi-asserted-by': 'crossref', 'first-page': '1139', 'DOI': '10.1126/science.abf6950', 'article-title': 'Recurrent deletions in the SARS-CoV-2 spike glycoprotein drive antibody ' 'escape', 'volume': '371', 'author': 'McCarthy', 'year': '2021', 'journal-title': 'Science'}, { 'issue': '7', 'key': '10.1016/j.lansea.2022.100036_bib0013', 'doi-asserted-by': 'crossref', 'first-page': '1124', 'DOI': '10.1016/j.chom.2021.06.006', 'article-title': 'SARS-CoV-2 spike L452R variant evades cellular immunity and increases ' 'infectivity', 'volume': '27', 'author': 'Motozono', 'year': '2021', 'journal-title': 'Cell Host Microbe'}, { 'key': '10.1016/j.lansea.2022.100036_bib0014', 'doi-asserted-by': 'crossref', 'first-page': '1', 'DOI': '10.3389/fcimb.2021.781429', 'article-title': 'SARS-COV-2 variants: differences and potential of immune evasion', 'volume': '11', 'author': 'Hirabara', 'year': '2022', 'journal-title': 'Front Cell Infect Microbiol'}, { 'key': '10.1016/j.lansea.2022.100036_bib0015', 'doi-asserted-by': 'crossref', 'first-page': 'e81', 'DOI': '10.1056/NEJMoa2108163', 'article-title': 'REGEN-COV antibody combination and outcomes in outpatients with ' 'COVID-19', 'volume': '385', 'author': 'Weinreich', 'year': '2021', 'journal-title': 'N Engl J Med'}, { 'key': '10.1016/j.lansea.2022.100036_bib0016', 'unstructured': 'Pfizer Press Release. Pfizer announces additional phase 2/3 study ' 'results confirming robust efficacy of novel COVID-19 oral antiviral ' 'treatment candidate in reducing risk of hospitalization or death, 14 ' 'December 2021. ' 'https://www.pfizer.com/news/press-release/press-release-detail/pfizer-announces-additional-phase-23-study-results. ' 'Accessed 18 February 2022.'}, { 'issue': '4', 'key': '10.1016/j.lansea.2022.100036_bib0017', 'doi-asserted-by': 'crossref', 'first-page': '372', 'DOI': '10.3390/v12040372', 'article-title': 'Virology, epidemiology, pathogenesis, and control of COVID-19', 'volume': '12', 'author': 'Jin', 'year': '2020', 'journal-title': 'Viruses'}, { 'key': '10.1016/j.lansea.2022.100036_bib0018', 'doi-asserted-by': 'crossref', 'first-page': '3099', 'DOI': '10.1007/s00405-021-06644-5', 'article-title': 'A sprayable Acid‑Oxidizing solution containing hypochlorous acid ' '(AOS2020) efficiently and safely inactivates SARS‑Cov‑2: a new ' 'potential solution for upper respiratory tract hygiene', 'volume': '278', 'author': 'Giarratana', 'year': '2021', 'journal-title': 'Eur Archi Oto-Rhino-Laryngology'}, { 'issue': '12', 'key': '10.1016/j.lansea.2022.100036_bib0019', 'doi-asserted-by': 'crossref', 'first-page': '1177', 'DOI': '10.1056/NEJMc2001737', 'article-title': 'SARS-CoV-2 viral load in upper respiratory specimens of infected ' 'patients', 'volume': '382', 'author': 'Zou', 'year': '2020', 'journal-title': 'N Engl J Med'}, { 'issue': '1', 'key': '10.1016/j.lansea.2022.100036_bib0020', 'doi-asserted-by': 'crossref', 'first-page': '170', 'DOI': '10.1186/s13054-020-02893-8', 'article-title': 'SARSCoV-2 viral load in sputum correlates with risk of COVID-19 ' 'progression', 'volume': '24', 'author': 'Yu', 'year': '2020', 'journal-title': 'Crit Care'}, { 'key': '10.1016/j.lansea.2022.100036_bib0021', 'doi-asserted-by': 'crossref', 'first-page': '1', 'DOI': '10.1002/advs.202003895', 'article-title': 'Nitric oxide to fight viral infections', 'volume': '8', 'author': 'Lisi', 'year': '2021', 'journal-title': 'Adv Sci'}, { 'key': '10.1016/j.lansea.2022.100036_bib0022', 'doi-asserted-by': 'crossref', 'first-page': '2', 'DOI': '10.21037/ajo-21-40', 'article-title': 'In vivo (human) and in vitro inactivation of SARS-CoV-2 with 0.5% ' 'povidone-iodine nasal spray', 'volume': '5', 'author': 'Friedland', 'year': '2022', 'journal-title': 'Aust J Otolaryng'}, { 'key': '10.1016/j.lansea.2022.100036_bib0023', 'unstructured': 'Utah State University Institute for Antiviral Research.Virucidal assay ' 'against Influenza A, HRV-14, and RSV. Report 2021-098. June 25, 2021 ' '[data on file].'}, { 'key': '10.1016/j.lansea.2022.100036_bib0024', 'unstructured': 'COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) ' 'Treatment Guidelines. National Institutes of Health. Available at: ' 'https://www.covid19treatmentguidelines.nih.gov/. Accessed 15 April ' '2022.'}, { 'key': '10.1016/j.lansea.2022.100036_bib0025', 'unstructured': 'SaNOtize study report - control test of NONS formulation against H1N1 ' '[2021, data on file].'}], 'container-title': 'The Lancet Regional Health - Southeast Asia', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://api.elsevier.com/content/article/PII:S2772368222000464?httpAccept=text/xml', 'content-type': 'text/xml', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://api.elsevier.com/content/article/PII:S2772368222000464?httpAccept=text/plain', 'content-type': 'text/plain', 'content-version': 'vor', 'intended-application': 'text-mining'}], 'deposited': { 'date-parts': [[2022, 7, 13]], 'date-time': '2022-07-13T06:23:48Z', 'timestamp': 1657693428000}, 'score': 1, 'resource': {'primary': {'URL': 'https://linkinghub.elsevier.com/retrieve/pii/S2772368222000464'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2022, 6]]}, 'references-count': 25, 'alternative-id': ['S2772368222000464'], 'URL': 'http://dx.doi.org/10.1016/j.lansea.2022.100036', 'relation': {}, 'ISSN': ['2772-3682'], 'container-title-short': 'The Lancet Regional Health - Southeast Asia', 'published': {'date-parts': [[2022, 6]]}, 'article-number': '100036'}
Loading..
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.
  or use drag and drop   
Submit