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

• ClinicalTrials.gov Identifier: NCT04347954
• Recruitment Status: Completed
• First Posted: April 15, 2020
• Results First Posted: October 21, 2021
• Last Update Posted: October 21, 2021
• Sponsor: Stanford University
• Information provided by (Responsible Party): Stanford University

Study Description

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."

Condition or disease	Intervention/treatment	Phase
COVID-19	Drug: Povidone-Iodine 2%; Drug: Povidone-Iodine 0.5%; Drug: Isotonic saline 0.9%	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 47 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Effect of PVP-I Nasal Sprays vs Normal Saline Nasal Sprays on SARS-CoV-2 Nasopharyngeal Titers
• Actual Study Start Date: August 15, 2020
• Actual Primary Completion Date: December 13, 2020
• Actual Study Completion Date: December 13, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Povidone-Iodine 2%; 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%; Two sprays to each nare of PVP-I 2% via nasal spray bottle, four times a day
Experimental: Povidone-Iodine 0.5%; 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%; Two sprays to each nare of PVP-I 0.5% via nasal spray bottle, four times a day
Placebo Comparator: Isotonic saline 0.9%; 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%; Two sprays to each nare of isotonic saline (0.9% NaCl) via nasal spray bottle, four times a day

Outcome Measures

Primary Outcome Measures :

1. Mean Cycle Threshold (Ct) Values Through Day 3 as a Measure of Change in Viral Titers of SARS-CoV-2 [ Time Frame: Day 1 (baseline), Day 1 (1 hour), Day 3 ]

   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.

Secondary Outcome Measures :

1. Count of Participants Experiencing Adverse Events of Interest After Nasal Sprays [ Time Frame: Assessed on days 3 and 5 ]
   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.
2. Count of Participants Experiencing Fevers as a Measure of Frequency of Symptoms Related to SARS-CoV-2 [ Time Frame: Assessed on days 3 and 5 ]
   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.'
3. Count of Participants Experiencing Chills as a Measure of Frequency of Symptoms Related to SARS-CoV-2 [ Time Frame: Assessed on days 3 and 5 ]
   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.'
4. Count of Participants Experiencing Fatigue as a Measure of Frequency of Symptoms Related to SARS-CoV-2 [ Time Frame: Assessed on days 3 and 5 ]
   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.'
5. Count of Participants Experiencing Loss of Sense of Smell as a Measure of Frequency of Symptoms Related to SARS-CoV-2 [ Time Frame: Assessed on days 3 and 5 ]
   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.'
6. Count of Participants Experiencing Loss of Sense of Taste as a Measure of Frequency of Symptoms Related to SARS-CoV-2 [ Time Frame: Assessed on days 3 and 5 ]
   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.'
7. Count of Participants Experiencing Nasal Congestion as a Measure of Frequency of Symptoms Related to SARS-CoV-2 [ Time Frame: Assessed on days 3 and 5 ]
   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.'
8. Count of Participants Experiencing Sore Throat as a Measure of Frequency of Symptoms Related to SARS-CoV-2 [ Time Frame: Assessed on days 3 and 5 ]
   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.'
9. Compliance With Study Drug Administration [ Time Frame: 5 days ]
   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.
10. Count of Participants Normosmia, Microsmia, or Anosmia as a Measure of Change in the University of Pennsylvania Smell Identification Test (UPSIT) [ Time Frame: Day 1 (baseline), Day 30 ]
    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).

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, California

Stanford Health Care

Stanford, California, United States, 94305

Sponsors and Collaborators

Stanford University

Investigators

• Principal Investigator: Jayakar V. Nayak, MD, PhD; Stanford University
• Principal Investigator: Neelaysh Vukkadala, MD; Stanford University

  Study Documents (Full-Text)

Documents provided by Stanford University:

Study Protocol and Statistical Analysis Plan  [PDF] July 10, 2020

More Information

• Responsible Party: Stanford University
• ClinicalTrials.gov Identifier: NCT04347954
• Other Study ID Numbers: IRB-56134
• First Posted: April 15, 2020
• Results First Posted: October 21, 2021
• Last Update Posted: October 21, 2021
• Last Verified: October 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Stanford University:

nasal spray; PVP-I; COVID-19

Additional relevant MeSH terms:

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Iodine; Cadexomer iodine; Povidone-Iodine; Povidone; Anti-Infective Agents, Local; Anti-Infective Agents; Trace Elements; Micronutrients; Physiological Effects of Drugs; Plasma Substitutes; Blood Substitutes