COVID-19
Conditions
Brief summary
This study is a two-arm, randomized, 2-phase study. Phase I will be double blinded clinical trial of the safety and efficacy of an antiseptic mouthwash solution on reducing SARS-CoV-2 load in COVID 19+ adult individuals. Phase II is designed as an open label trial, and all subjects will receive the active mouthwash.
Interventions
DRUGMouth rinse
Subjects will be asked to rinse/gargle one time with 10 mL of assigned mouth rinse for 30 seconds.
Sponsors
Avrio Health
University of Pennsylvania
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Able and willing to provide informed consent prior to initiation of study procedures. 2. Stated willingness to comply with all study procedures and availability for the duration of the study. 3. Male or female, aged 18 years and older. 4. Clinical diagnosis of COVID-19 infection confirmed with a positive point of care test. 5. Confirmed diagnosis within 5 days of baseline visit (within 5 days of COVID-19 test) and at least one clinical COVID-19 symptom \[\*Signs and symptoms of COVID-19 present at illness onset vary, but over the course of the disease, most people will experience the following: fever or chills, cough, shortness of breath or difficulty breathing, fatigue, muscle or body aches, headache, new loss of taste of smell, sore throat, congestion or runny nose, nausea or vomiting and diarrhea.\] 6. Presents with a minimum of six natural teeth. 7. Ability to rinse/gargle with study products. 8. Not using mouth rinse/gargling solutions at the time of enrollment. 9. Not taking antimicrobial medications (antibacterial, antiviral, antibiotics, including hydroxychloroquine) at time of enrollment. 10. Ability to participate in the study and come to site during Phase I of the study for collection of swabs and saliva. 11. Willing to use an acceptable method of birth control throughout duration of the study. Acceptable methods include hormonal contraceptives, barrier methods, abstinence, or other effective methods approved by the PI. 12. If continuing to Phase II of the trial, ability to continue using study products for 1 week (+ 3 days). (Participants do not have to agree to participate in Phase II in order to participate in Phase I.) 13. If continuing to Phase II of the trial, agree to receive text messages/phone calls containing questionnaires regarding compliance and use of study product, and reminders, able to complete virtual follow-up study visit for collection of outcomes data.
Exclusion criteria
1. Individuals receiving antiviral medications 2. Pregnant or breastfeeding women (for premenopausal women of childbearing potential, pregnancy status to be confirmed through a urine pregnancy test during the study visit) 3. Inability to comply with study protocol 4. Having an allergy to any of the study mouthwash ingredients 5. Having any thyroid condition. 6. Presents with a current suspicious oral lesion at the examiner's discretion, and/or currently undergoing radiation therapy for head or neck cancer, and/or has received radiation therapy to the head or neck (including radioactive iodine therapy).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| [PCR Saliva] Percent Change From Baseline Ct Viral Targets | 60 minutes after intervention | The primary endpoint is the percentage reduction of SARS-Co-V-2 load in saliva at 60 minutes (post-intervention) compared to baseline between the PVP-I mouthwash versus the placebo mouthwash. For this outcome, Cycle Threshold is a proxy for SARS-Co-V-2 load. A positive percent change from baseline Cycle Threshold indicates a decrease from baseline SAR-Co-V2. \[Quick SARS-CoV-2 rRT-PCR Kit (Zymo Research, Cat. No. R3011)\]. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| [PCR Saliva] Percent Change From Baseline Cycle Threshold at 5 and 30 Minutes Post Intervention | 5 and 30 minutes post-intervention | The secondary endpoints are the percentage reduction of SARS-Co-V-2 load in saliva at 5 and 30 minutes (post-intervention) compared to baseline between the PVP-I mouthwash versus the placebo mouthwash. For this outcome, Cycle Threshold is a proxy for SARS-Co-V-2 load. A positive percent change from baseline Cycle Threshold indicated a decrease from baseline SARS-Co-V-2. |
Other
| Measure | Time frame | Description |
|---|---|---|
| [Oropharyngeal Swab] Percent Change From Baseline Log10 Antigens | 5, 30, and 60 minutes post intervention | The secondary endpoints are the percentage reduction in SARS-Co-V-2 antigens obtained from oropharyngeal swab at 5, 30 and 60-minutes (post-intervention) compared to baseline within each treatment group. |
| [Nasal Swab] Log10 Antigens | 5, 30, 60 minutes post intervention | In the context of the study, the antigen data was used to validate infectivity, as this site was not treated. The pre-specified outcomes are the percentage reduction in SARS-Co-V-2 antigens obtained from nasal swab at 5, 30 and 60-minutes (post-intervention) compared to baseline within each treatment group. |
Countries
United States
Participant flow
Recruitment details
Recruitment was from 2/7/2022 to 7/7/2022. Primary recruitment was through the University of Pennsylvania testing sites, community testing sites, and community partners. We also placed flyers/advertisements within our hospitals and dental clinics, including our community health centers outside the school, and relevant social media pages.
Participants by arm
| Arm | Count |
|---|---|
| Povidone-iodine 0.5% Antiseptic Mouth Rinse Subjects will be asked to rinse/gargle one time with 10 mL of Povidone-iodine 0.5% antiseptic mouth rinse for 30 seconds.
Mouth rinse: Subjects will be asked to rinse/gargle one time with 10 mL of assigned mouth rinse for 30 seconds. | 21 |
| Placebo Subjects will be asked to rinse/gargle one time with 10 mL of placebo mouth rinse for 30 seconds.
Mouth rinse: Subjects will be asked to rinse/gargle one time with 10 mL of assigned mouth rinse for 30 seconds. | 19 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Phase II (Open Label) | Lost to Follow-up | 1 | 0 |
| Phase II (Open Label) | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Povidone-iodine 0.5% Antiseptic Mouth Rinse | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 30.6 Years STANDARD_DEVIATION 11.4 | 32.4 Years STANDARD_DEVIATION 12.3 | 31.5 Years STANDARD_DEVIATION 12.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants | 19 Participants | 39 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| [Nasal Swab] Log10 Antigens | 6.2 Log10 Copies/mL | 6.3 Log10 Copies/mL | 6.2 Log10 Copies/mL |
| [Oropharyngeal Swab] Log10 Antigens | 4.3 Log10 Copies/mL | 4.2 Log10 Copies/mL | 4.3 Log10 Copies/mL |
| (PCR Saliva) Ct Viral target Means (SD) at baseline | 26.6 Cycle Threshold STANDARD_DEVIATION 4.7 | 25.1 Cycle Threshold STANDARD_DEVIATION 5.6 | 25.9 Cycle Threshold STANDARD_DEVIATION 5.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 12 Participants | 7 Participants | 19 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 5 Participants | 10 Participants | 15 Participants |
| Sex: Female, Male Female | 16 Participants | 12 Participants | 28 Participants |
| Sex: Female, Male Male | 5 Participants | 7 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 | 0 / 37 |
| other Total, other adverse events | 0 / 40 | 0 / 40 | 4 / 37 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 | 0 / 37 |
Outcome results
Primary
[PCR Saliva] Percent Change From Baseline Ct Viral Targets
The primary endpoint is the percentage reduction of SARS-Co-V-2 load in saliva at 60 minutes (post-intervention) compared to baseline between the PVP-I mouthwash versus the placebo mouthwash. For this outcome, Cycle Threshold is a proxy for SARS-Co-V-2 load. A positive percent change from baseline Cycle Threshold indicates a decrease from baseline SAR-Co-V2. \[Quick SARS-CoV-2 rRT-PCR Kit (Zymo Research, Cat. No. R3011)\].
Time frame: 60 minutes after intervention
Population: Participants were randomized to Povidone-iodine or Placebo (saline) in a 1:1 ratio. Three participants had non-evaluable baseline Cycle Threshold-values and one value was missing at 60 minutes so they were excluded from the analysis of the outcome.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Povidone-iodine 0.5% Antiseptic Mouth Rinse | [PCR Saliva] Percent Change From Baseline Ct Viral Targets | 5.8 % Change from Baseline Cycle Threshold |
| Placebo | [PCR Saliva] Percent Change From Baseline Ct Viral Targets | 1.3 % Change from Baseline Cycle Threshold |
p-value: 0.28795% CI: [-4, 13]t-test, 2 sided
Secondary
[PCR Saliva] Percent Change From Baseline Cycle Threshold at 5 and 30 Minutes Post Intervention
The secondary endpoints are the percentage reduction of SARS-Co-V-2 load in saliva at 5 and 30 minutes (post-intervention) compared to baseline between the PVP-I mouthwash versus the placebo mouthwash. For this outcome, Cycle Threshold is a proxy for SARS-Co-V-2 load. A positive percent change from baseline Cycle Threshold indicated a decrease from baseline SARS-Co-V-2.
Time frame: 5 and 30 minutes post-intervention
Population: Participants were randomized to Povidone-iodine or Placebo (saline) in a 1:1 ratio. Three participants had non-evaluable baseline Ct-values so were excluded from the analysis of these secondary outcomes.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Povidone-iodine 0.5% Antiseptic Mouth Rinse | [PCR Saliva] Percent Change From Baseline Cycle Threshold at 5 and 30 Minutes Post Intervention | 5 minutes post intervention | 3.3 % Change from Baseline Cycle Threshold |
| Povidone-iodine 0.5% Antiseptic Mouth Rinse | [PCR Saliva] Percent Change From Baseline Cycle Threshold at 5 and 30 Minutes Post Intervention | 30 minutes post intervention | 2.0 % Change from Baseline Cycle Threshold |
| Placebo | [PCR Saliva] Percent Change From Baseline Cycle Threshold at 5 and 30 Minutes Post Intervention | 5 minutes post intervention | 1.7 % Change from Baseline Cycle Threshold |
| Placebo | [PCR Saliva] Percent Change From Baseline Cycle Threshold at 5 and 30 Minutes Post Intervention | 30 minutes post intervention | -0.6 % Change from Baseline Cycle Threshold |
Comparison: 5 minutes post interventionp-value: 0.62595% CI: [-5.2, 8.6]t-test, 2 sided
Comparison: 30 minutes post interventionp-value: 0.52695% CI: [-5.5, 10.5]t-test, 2 sided
Other Pre-specified
[Nasal Swab] Log10 Antigens
In the context of the study, the antigen data was used to validate infectivity, as this site was not treated. The pre-specified outcomes are the percentage reduction in SARS-Co-V-2 antigens obtained from nasal swab at 5, 30 and 60-minutes (post-intervention) compared to baseline within each treatment group.
Time frame: 5, 30, 60 minutes post intervention
Population: Participants were randomized to Povidone-iodine or Placebo (saline) in a 1:1 ratio.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Povidone-iodine 0.5% Antiseptic Mouth Rinse | [Nasal Swab] Log10 Antigens | 5 minutes post intervention | 3.1 % Change from Baseline Log10 Antigens |
| Povidone-iodine 0.5% Antiseptic Mouth Rinse | [Nasal Swab] Log10 Antigens | 30 minutes post intervention | 1.8 % Change from Baseline Log10 Antigens |
| Povidone-iodine 0.5% Antiseptic Mouth Rinse | [Nasal Swab] Log10 Antigens | 60 minutes post intervention | 1.5 % Change from Baseline Log10 Antigens |
| Placebo | [Nasal Swab] Log10 Antigens | 5 minutes post intervention | -4.1 % Change from Baseline Log10 Antigens |
| Placebo | [Nasal Swab] Log10 Antigens | 30 minutes post intervention | -0.7 % Change from Baseline Log10 Antigens |
| Placebo | [Nasal Swab] Log10 Antigens | 60 minutes post intervention | -3.6 % Change from Baseline Log10 Antigens |
Comparison: Povidone-iodine 5 minutes post-interventionp-value: 0.21295% CI: [-2.2, 5.8]Signed Rank
Comparison: Povidone-iodine 30 minutes post-interventionp-value: 0.33495% CI: [-2.3, 6.9]Signed Rank
Comparison: Povidone-iodine 60 minutes post-interventionp-value: 0.26995% CI: [-3.1, 6.8]Signed Rank
Comparison: Placebo 5 minutes post-interventionp-value: 0.02695% CI: [-7.1, -0.7]Signed Rank
Comparison: Placebo 30 minutes post-interventionp-value: 0.18295% CI: [-9.4, 2]Signed Rank
Comparison: Placebo 60 minutes post-interventionp-value: 0.35395% CI: [-7.7, 4]Signed Rank
Other Pre-specified
[Oropharyngeal Swab] Percent Change From Baseline Log10 Antigens
The secondary endpoints are the percentage reduction in SARS-Co-V-2 antigens obtained from oropharyngeal swab at 5, 30 and 60-minutes (post-intervention) compared to baseline within each treatment group.
Time frame: 5, 30, and 60 minutes post intervention
Population: Participants were randomized to Povidone-iodine or Placebo (saline) in a 1:1 ratio.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Povidone-iodine 0.5% Antiseptic Mouth Rinse | [Oropharyngeal Swab] Percent Change From Baseline Log10 Antigens | 5 minutes post intervention | 0.04 % Change from Baseline Median Log10 |
| Povidone-iodine 0.5% Antiseptic Mouth Rinse | [Oropharyngeal Swab] Percent Change From Baseline Log10 Antigens | 30 minutes post intervention | 5.4 % Change from Baseline Median Log10 |
| Povidone-iodine 0.5% Antiseptic Mouth Rinse | [Oropharyngeal Swab] Percent Change From Baseline Log10 Antigens | 60 minutes post intervention | -4.9 % Change from Baseline Median Log10 |
| Placebo | [Oropharyngeal Swab] Percent Change From Baseline Log10 Antigens | 5 minutes post intervention | -2.4 % Change from Baseline Median Log10 |
| Placebo | [Oropharyngeal Swab] Percent Change From Baseline Log10 Antigens | 30 minutes post intervention | -6.6 % Change from Baseline Median Log10 |
| Placebo | [Oropharyngeal Swab] Percent Change From Baseline Log10 Antigens | 60 minutes post intervention | -8.6 % Change from Baseline Median Log10 |
Comparison: Povidone-iodine: 5 minutes Post-Interventionp-value: 0.51195% CI: [-4.2, 8.1]Signed Rank
Comparison: Povidone-iodine: 30 minutes post-interventionp-value: 0.40895% CI: [-10.7, 18.6]Signed Rank
Comparison: Povidone-iodine: 60 minutes post-interventionp-value: 0.90795% CI: [-15.2, 17.5]Signed Rank
Comparison: Placebo: 5 minutes post interventionp-value: 0.00895% CI: [-6.5, -0.9]Signed Rank
Comparison: Placebo: 30 minutes post-interventionp-value: 0.0895% CI: [-10.1, -2.2]Signed Rank
Comparison: Placebo: 60 minutes post-interventionp-value: 0.00195% CI: [-22.3, -3.9]Signed Rank