Clinical trial NCT04802408: SARS-Cov-2 (COVID-19) Nasal Pharyngeal and Oral Pharyngeal Wash (SNOW) Trial
Official title: SARS-Cov-2 (COVID-19) Nasal Pharyngeal and Oral Pharyngeal Wash (SNOW) Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Covid19
SARS-CoV Infection
Keywords: Covid 19
SARS-CoV-2
Viral Load
Nasal Rinse
Oral Rinse
Lead sponsor: Milton S. Hershey Medical Center
Sponsor class: OTHER
Collaborators: name: AXIOM Real Time Metrics
name: Analytica Ventures LLC
First posted: 2021-03-17
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: This is a prospective, randomized, controlled, 2x2 factorial, phase 2/phase 3 trial to compare the impact of a 4-day intervention of nasal washes with 1% baby shampoo solution and/or oropharyngeal gargles with Listerine Antiseptic® solution compared to that of nasal washes with buffered saline solution and/or oropharyngeal rinses with saline solution on naso-oropharyngeal SARS-CoV-2 viral load in a population of adults (aged 18-65 years) with SARS-CoV-2 infection diagnosed within 5 days who are asymptomatic or mildly symptomatic for COVID-19 disease.
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Viral Load Change from baseline
timeFrame: 5 days
Secondary outcomes:
measure: 4-day trend in viral load change
timeFrame: 5 days
measure: Levels of live virus (viral infectivity titer)
timeFrame: 15 minutes
measure: Levels of live virus (viral infectivity titer)
timeFrame: 1 day
measure: The tolerability of the intervention measured using the validated Sino-nasal outcome test (SNOT-22) scale.
timeFrame: 5 days
measure: Compliance as measured by percent of expected washes completed
timeFrame: 5 days
measure: Compliance as measured by percentage of randomized participants that withdrew consent and elected not to continue in the study.
timeFrame: 5 days
measure: Acceptability of the intervention as measured by 7 item questionnaire based an acceptability framework described by Sekhon (2017)
timeFrame: 6 days
Other outcomes:
Locations:
city: Hershey
country: United States
facility: Penn State Health Milton S. Hershey Medical Center
state: Pennsylvania
city: State College
country: United States
facility: Penn State
state: Pennsylvania
Study officials:
affiliation: Penn State College of Medicine
name: Rena Kass, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
citation: 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.
citation: 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.
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
citation: "Tracking the Coronavirus at U.S. Colleges and Universities." New York Times. Last updated Dec. 11, 2020.