PVP-I Nasal Sprays and SARS-CoV-2 Nasopharyngeal Titers (for COVID-19)

Study Overview
=================
Brief Summary
-----------------
The study aims to determine the safety and efficacy of povidone-iodine (PVP-I) containing nasal sprays as compared to isotonic saline nasal sprays in COVID-19 positive patients. The primary outcome measure is SARS-CoV-2 viral titers in the nasal cavity and nasopharynx. In vitro studies have shown PVP-I to be highly virucidal against the viruses which cause SARS and MERS. Additionally, clinical studies have shown PVP-I saline sprays to be well tolerated in human subjects. PVP-I oral rinses and sprays have been trialed as methods to reduce the incidence and symptoms of viruses which cause the common cold.

Official Title
-----------------
Effect of PVP-I Nasal Sprays vs Normal Saline Nasal Sprays on SARS-CoV-2 Nasopharyngeal Titers

Conditions
-----------------
COVID-19

Intervention / Treatment
-----------------
* Drug: Povidone-Iodine 2%
* Drug: Povidone-Iodine 0.5%
* Drug: Isotonic saline 0.9%


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of COVID-19 by lab test within 5 days of study participation Exclusion Criteria: Allergy to iodine, shellfish, or food dye Receiving intranasal steroids Sinus surgery within 30 days of beginning the study Intubated at the time of enrollment Pregnancy Participation in other COVID-19 studies - to be determined on a case by case basis

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Povidone-Iodine 2%<br>Participants will administer PVP-I 2% nasal spray for 5 days. Nasopharyngeal swabs will be taken on Day 1 at baseline, Day 1 at four hours post-first dose, and Day 5. Participants will complete a daily symptom journal from Day 1 through Day 5. | Drug: Povidone-Iodine 2%<br>* Two sprays to each nare of PVP-I 2% via nasal spray bottle, four times a day<br>|
| Experimental: Povidone-Iodine 0.5%<br>Participants will administer PVP-I 0.5% nasal spray for 5 days. Nasopharyngeal swabs will be taken on Day 1 at baseline, Day 1 at four hours post-first dose, and Day 5. Participants will complete a daily symptom journal from Day 1 through Day 5 | Drug: Povidone-Iodine 0.5%<br>* Two sprays to each nare of PVP-I 0.5% via nasal spray bottle, four times a day<br>|
| Placebo Comparator: Isotonic saline 0.9%<br>Participants will administer two sprays of isotonic saline nasal spray for 5 days. Nasopharyngeal swabs will be taken on Day 1 at baseline, Day 1 at four hours post-first dose, and Day 5. Participants will complete a daily symptom journal from Day 1 through Day 5. | Drug: Isotonic saline 0.9%<br>* Two sprays to each nare of isotonic saline (0.9% NaCl) via nasal spray bottle, four times a day<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Cycle Threshold (Ct) Values Through Day 3 as a Measure of Change in Viral Titers of SARS-CoV-2 | Nasopharyngeal swabs were obtained and quantitative reverse transcription-polymerase chain reaction (RT-PCR) testing was performed to determine the viral load in the nasopharynx. Cycle threshold (Ct) denotes how many PCR cycles are required before the SARS-CoV-2 viral RNA reached a detectable level. Higher Ct values correspond to lower viral copy numbers. For reference, Ct values of 20 correspond to  2.12 x 106 viral copies per milliliter, while a Ct value of 40 is undetectable and is considered the lower limit of detection of this RT-PCR test for SARS-CoV-2. | Day 1 (baseline), Day 1 (1 hour), Day 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Count of Participants Experiencing Adverse Events of Interest After Nasal Sprays | Participants were asked on day 3 whether they experienced the adverse event since baseline, then asked on day 5 whether they experienced the adverse event since day 3 (collected by questionnaire). Adverse events of interest include: Nasal burning/pain, headaches, ear pain, sneezing, and nose bleeds. | Assessed on days 3 and 5 | 
| Count of Participants Experiencing Fevers as a Measure of Frequency of Symptoms Related to SARS-CoV-2 | Count of participants that experienced fevers at either mild, moderate, or severe intensity. Participants were asked on day 3 whether they experienced the symptom since baseline, then asked on day 5 whether they experienced the symptom since day 3. Participants rated the severity of their symptoms on a 4-point Likert scale with 1 representing 'not experiencing that symptom,' 2 representing mild symptoms, 3 representing 'moderate symptoms,' and 4 representing 'severe symptoms.' | Assessed on days 3 and 5 | 
| Count of Participants Experiencing Chills as a Measure of Frequency of Symptoms Related to SARS-CoV-2 | Count of participants that experienced chills at either mild, moderate, or severe intensity. Participants were asked on day 3 whether they experienced the symptom since baseline, then asked on day 5 whether they experienced the symptom since day 3. Participants rated the severity of their symptoms on a 4-point Likert scale with 1 representing 'not experiencing that symptom,' 2 representing mild symptoms, 3 representing 'moderate symptoms,' and 4 representing 'severe symptoms.' | Assessed on days 3 and 5 | 
| Count of Participants Experiencing Fatigue as a Measure of Frequency of Symptoms Related to SARS-CoV-2 | Count of participants that experienced fatigue at either mild, moderate, or severe intensity. Participants were asked on day 3 whether they experienced the symptom since baseline, then asked on day 5 whether they experienced the symptom since day 3. Participants rated the severity of their symptoms on a 4-point Likert scale with 1 representing 'not experiencing that symptom,' 2 representing mild symptoms, 3 representing 'moderate symptoms,' and 4 representing 'severe symptoms.' | Assessed on days 3 and 5 | 
| Count of Participants Experiencing Loss of Sense of Smell as a Measure of Frequency of Symptoms Related to SARS-CoV-2 | Count of participants that experienced loss of sense of smell at either mild, moderate, or severe intensity. Participants were asked on day 3 whether they experienced the symptom since baseline, then asked on day 5 whether they experienced the symptom since day 3. Participants rated the severity of their symptoms on a 4-point Likert scale with 1 representing 'not experiencing that symptom,' 2 representing mild symptoms, 3 representing 'moderate symptoms,' and 4 representing 'severe symptoms.' | Assessed on days 3 and 5 | 
| Count of Participants Experiencing Loss of Sense of Taste as a Measure of Frequency of Symptoms Related to SARS-CoV-2 | Count of participants that experienced loss of sense of taste at either mild, moderate, or severe intensity. Participants were asked on day 3 whether they experienced the symptom since baseline, then asked on day 5 whether they experienced the symptom since day 3. Participants rated the severity of their symptoms on a 4-point Likert scale with 1 representing 'not experiencing that symptom,' 2 representing mild symptoms, 3 representing 'moderate symptoms,' and 4 representing 'severe symptoms.' | Assessed on days 3 and 5 | 
| Count of Participants Experiencing Nasal Congestion as a Measure of Frequency of Symptoms Related to SARS-CoV-2 | Count of participants that experienced nasal congestion at either mild, moderate, or severe intensity. Participants were asked on day 3 whether they experienced the symptom since baseline, then asked on day 5 whether they experienced the symptom since day 3. Participants rated the severity of their symptoms on a 4-point Likert scale with 1 representing 'not experiencing that symptom,' 2 representing mild symptoms, 3 representing 'moderate symptoms,' and 4 representing 'severe symptoms.' | Assessed on days 3 and 5 | 
| Count of Participants Experiencing Sore Throat as a Measure of Frequency of Symptoms Related to SARS-CoV-2 | Count of participants that experienced sore throat at either mild, moderate, or severe intensity. Participants were asked on day 3 whether they experienced the symptom since baseline, then asked on day 5 whether they experienced the symptom since day 3. Participants rated the severity of their symptoms on a 4-point Likert scale with 1 representing 'not experiencing that symptom,' 2 representing mild symptoms, 3 representing 'moderate symptoms,' and 4 representing 'severe symptoms.' | Assessed on days 3 and 5 | 
| Compliance With Study Drug Administration | Participants were asked to estimated doses completed at day 5 (0-25%, 26-50%, 51-75%, or 76-100%). The count of participants who estimated their compliance to be within each range is reported. | 5 days | 
| Count of Participants Normosmia, Microsmia, or Anosmia as a Measure of Change in the University of Pennsylvania Smell Identification Test (UPSIT) | Participants scratch test cards and attempt to identify the smell from a multiple choice set of options. Their scores are then computed and categorized as normosmia (normal), mild, moderate, or severe microsmia (loss of smell), or anosmia (total loss of smell). | Day 1 (baseline), Day 30 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
nasal spray, PVP-I, COVID-19