SARS-Cov-2 (COVID-19) Nasal Pharyngeal and Oral Pharyngeal Wash (SNOW) Trial

Covid19 Clinical Trial

— SNOW  

Official title:

SARS-Cov-2 (COVID-19) Nasal Pharyngeal and Oral Pharyngeal Wash (SNOW) Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04802408
• Other study ID #: STUDY00016947
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: October 1, 2021
• Est. completion date: May 30, 2025

Study information

• Verified date: September 2023
• Source: Milton S. Hershey Medical Center
• Contact: Rena Kass, MD
• Phone: 717-531-8815
• Email: rkass[@]pennstatehealth.psu.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Adults (aged 18-65 years) recently diagnosed with SARS-CoV-2 infection who use a 4-day combined intervention of nasal washes with 1% baby shampoo solution and oral gargles with Listerine Antiseptic® will have a reduced SARS-CoV-2 viral load compared to those using nasal and oral washes with normal saline. This combined intervention should be acceptable, tolerable and safe in this population. To test this, investigators are conducting a trial comparing the efficacy of a number of washes in reducing the oral and nasal SARS-CoV-2 viral load among adults.

Description:

Investigators have demonstrated the in vitro viridical efficacy of both Listerine Antiseptic® and 1% dilute baby shampoo solution, a commonly used nasal rinse, against a SARS-CoV-2 surrogate and Meister et al. have similar findings with SARS-CoV-2. With an urgent need to expand the armamentarium of widely available, low-cost interventions, that are safe for repeated human use and reduce viral transmission, investigators seek to determine the impact of a combined regimen of oral and nasal rinsing with these agents on naso-oropharyngeal viral loads in adults (aged 18-65 years) with SARS-CoV-2 infection.

Rationale for the intervention: a combination of nasal washes with 1% solution of baby shampoo and oral washes with Listerine Antiseptic® Available data indicate that SARS-CoV-2 is most likely to spread, like most other common respiratory viruses, primarily through respiratory droplet transmission. With the naso-oropharynx being both the primary site from which the virus is expelled by people with infection and the nasal and oral mucosal cells is one of the sites of initial infection and viral replication. Specifically the ACE2 receptor, that SARS-CoV-2 binds for cell entry, are highly concentrated in the goblet and ciliated cells of the nose and on the tongue. Thus a reduction of viral load through topical treatment of these sites could potentially lead to reduced transmission of SARS-CoV-2.

Each of the two proposed agents to be tested have independently demonstrated virucidal activity with short contact time in vitro. With over 140 years of usage worldwide, the safety of gargles with Listerine Antiseptic® is well established. Topical nasal lavage using a dilute solution of baby shampoo has also been demonstrated to be safe and effective both as a mucoactive and microbicidal agent. Both agents are readily available and cost-efficient for daily usage.

While there are a number of ongoing trials of interventions with similar approaches, most of them focus on a single intervention, either nasal or oral rinses. This potentially leaves a viral reservoir in the untreated site, with the potential for recolonizing the entire oronasopharynx thereby limiting the utility of intervention. There is a single trial treating both the oral and nasal spaces. However, the agent being tested is povidone-iodine, that has known adverse effects limiting its use. These adverse effects include discoloration of teeth, ciliary dysfunction, iodine overdose and possible drug interactions, such as with lithium.

Investigators believe that the proposed intervention for this study is likely to be well-tolerated, highly acceptable and result in elimination from the key sites in the oronasopharynx. Additionally, the proposed four-arm design will allow investigators to compare the combined intervention with each of the component treatments. A decision was made to use saline rinses as the control arm as the investigator's in vitro data revealed that saline had no virucidal activity against human coronavirus.

Based on recent literature describing viral load dynamics during the course of SARS-CoV-2 infection, investigators believe that a four-day trial, initiated within 5 days of Covid testing, will allow for the testing of change in viral load close to/or within the 7-10 day timeframe of greatest SARS-CoV-2 viral load. The study period will also fall within the 2-3 week period of the mean duration of SARS-CoV-2. Mohamed et al suggest that 4 days of oral Listerine washes three times daily may be efficacious in decreasing viral load. Several other rinse trials also employ this rinse frequency. The rinse times of 60 secs and 30 secs for nasal wash with 1% dilute baby shampoo and oral Listerine respectively, are based on the successful virus reduction demonstrated at these contact times in vitro.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: May 30, 2025
• Est. primary completion date: May 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. A first-time positive test for SARS-CoV-2 infection within 5 days of enrollment

2. Adults who are =18 -65 years of age

3. Currently in isolation

4. Symptomatic or asymptomatic from SARS-CoV-2

Exclusion Criteria:

1. History of nasal or sinus surgery

2. Non-English speaking

3. Lack of electronic device (computer, mobile phone etc.) on which to access an app for study data collection.

4. Adults that need inpatient care for COVID-19 or any of its complications.

5. Adults that give a history of being unable to tolerate gargles or nasal washes.

6. Adults who do not give informed consent for study participation.

7. History of a Covid vaccine booster

8. A history of use of nasal or oral washes after SARS-CoV-2 test sample collection.

9. Prisoners

10. Adults that give history of current pregnancy (NO KNOWN CONTRAINDICATION TO PREGNANCY)

11. History of monoclonal antibody treatment

12. History of or current molnupiravir treatment

Related Conditions & MeSH terms

• COVID-19
• Covid19
• SARS-CoV Infection
• Severe Acute Respiratory Syndrome

Intervention

Combination Product:
• Shampoo and saline
Nasal washes with 1% baby shampoo solution and oropharyngeal gargles with saline solution
• Saline and Listerine
Nasal washes with buffered saline solution and oropharyngeal gargles with Listerine Antiseptic® solution
• Shampoo and Listerine
Nasal washes with 1% baby shampoo solution and oropharyngeal gargles with Listerine Antiseptic® solution
• Saline and Saline
Nasal washes with buffered saline solution and oropharyngeal gargles with saline solution

Locations

Country	Name	City	State
United States	Penn State Health Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Penn State	State College	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
Milton S. Hershey Medical Center	Analytica Ventures LLC, AXIOM Real Time Metrics

Country where clinical trial is conducted

United States, 

References & Publications (6)

"Tracking the Coronavirus at U.S. Colleges and Universities." New York Times. Last updated Dec. 11, 2020.

Cevik M, Tate M, Lloyd O, Maraolo AE, Schafers J, Ho A. SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: a systematic review and meta-analysis. Lancet Microbe. 2021 Jan;2(1):e13-e22. doi: 10.1016/S2666-5247(20)30172-5. Epub 2020 Nov 19. — View Citation

Meister TL, Bruggemann Y, Todt D, Conzelmann C, Muller JA, Gross R, Munch J, Krawczyk A, Steinmann J, Steinmann J, Pfaender S, Steinmann E. Virucidal Efficacy of Different Oral Rinses Against Severe Acute Respiratory Syndrome Coronavirus 2. J Infect Dis. 2020 Sep 14;222(8):1289-1292. doi: 10.1093/infdis/jiaa471. Erratum In: J Infect Dis. 2021 Feb 13;223(3):541. — View Citation

Mohamed N. Early viral clearance among Covid-19 patients when gargling with povidone-iodine and essential oils: A pilot clinical trial. medRxiv 2020.09.07.20180448; https://doi.org/10.1101/2020.09.07.20180448 preprint

Shrestha NK, Marco Canosa F, Nowacki AS, Procop GW, Vogel S, Fraser TG, Erzurum SC, Terpeluk P, Gordon SM. Distribution of Transmission Potential During Nonsevere COVID-19 Illness. Clin Infect Dis. 2020 Dec 31;71(11):2927-2932. doi: 10.1093/cid/ciaa886. — View Citation

Sungnak W, Huang N, Becavin C, Berg M, Queen R, Litvinukova M, Talavera-Lopez C, Maatz H, Reichart D, Sampaziotis F, Worlock KB, Yoshida M, Barnes JL; HCA Lung Biological Network. SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nat Med. 2020 May;26(5):681-687. doi: 10.1038/s41591-020-0868-6. Epub 2020 Apr 23. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Viral Load Change from baseline	Primary Study Endpoints The primary endpoint is the change from baseline in measured viral load in the nose and mouth of adults aged 18-65 years with SARS-CoV-2 infection after 4 days of washes (Day 5 vs Day 1). This will be measured using quantitative PCR (qPCR) analysis, with standard procedures to make cDNA copies of the viral genomic RNA and using CDC recommended primers qPCR to determine viral load. Four separate regimens will be evaluated: 1% dilute baby shampoo nasal wash and a saline oral gargle; buffered saline nasal wash and Listerine oral gargle; 1% dilute baby shampoo nasal wash and Listerine oral gargle; and buffered saline nasal wash and saline oral gargle.	5 days
Secondary	4-day trend in viral load change	The 4-day trend in viral load change in the nose and mouth of adults with SARS-CoV-2 infection measured with qPCR each morning on Days 1, 2, 3 and 4, as well as the post-intervention level measured on Day 5.	5 days
Secondary	Levels of live virus (viral infectivity titer)	The change in measured levels of live virus (viral infectivity titer), detected from the nose and mouth after the first wash on the morning of Day 1 compared to live virus detected before the first wash on Day 1 (baseline) . Infectivity will be measured by the number of plaque forming units in Vero cells	15 minutes
Secondary	Levels of live virus (viral infectivity titer)	The change in measured levels of live virus (viral infectivity titer) detected from the nose and mouth 24 hours after the initiation of rinses on Day 1. Infectivity will be measured by the number of plaque forming units in Vero cells	1 day
Secondary	The tolerability of the intervention measured using the validated Sino-nasal outcome test (SNOT-22) scale.	The tolerability of the intervention measured using the validated Sino-nasal outcome test (SNOT-22) scale.; The minimum score is 0 and the maximum score is 110, where a higher score is less tolerable.	5 days
Secondary	Compliance as measured by percent of expected washes completed	Participant compliance to the intervention will be calculated by percent of expected washes completed.	5 days
Secondary	Compliance as measured by percentage of randomized participants that withdrew consent and elected not to continue in the study.	Compliance will be measured by determining the percentage of randomized participants that withdrew consent and elected not to continue in the study.	5 days
Secondary	Acceptability of the intervention as measured by 7 item questionnaire based an acceptability framework described by Sekhon (2017)	The acceptability of the intervention, using a structured 7 item questionnaire based on the acceptability framework described by Sekhon (2017). The minimum score is 7 and the maximum score is 35. With the higher score being more acceptible.	6 days