COVID-19: Povidone-Iodine Intranasal Prophylaxis in Front-line Healthcare Personnel and Inpatients
Condition: COVID-19; SARS-CoV 2
MeSH terms: COVID-19
Study type: Interventional
Phase: Phase 2

Summary: 
      Povidone-iodine (PVP-I) is a broad-spectrum antiseptic with activity against bacteria, fungi,
      and viruses. It has been previously used in both intranasal preparations against Methicillin
      Resistant Staphylococcus Aureus (MRSA) as well as oral preparations in in-vitro studies of
      Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), Middle Eastern Respiratory Syndrome
      Coronavirus (MERS-CoV), influenza H1N1, and rotavirus with good efficacy. This study will
      evaluate the efficacy of PVP-I as prophylaxis in Coronavirus Disease 2019 (COVID19)-negative
      front-line health care workers, hospital patients, and community members.
    

Detailed description: 
      The COVID-19 pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus - 2
      (SARS-CoV-2), has been implicated in over 12 million cases and counting in the United States
      alone and has killed at least 1300 health care workers and >250,000 citizens. This, added to
      the national shortage of personal protective equipment (PPE) and the need to reuse PPE, lends
      to the significantly increased risk to healthcare providers. At the beginning of this trial,
      there were only 360,000 cases.

      The highest concentration of viral particles resides within the nasopharynx. The virus is
      thought to spread via respiratory droplets with the potential for transmission via inhalation
      of droplets, contact to the nose and mouth with infected materials, and airborne
      transmission. Given that frontline workers are involved in high-risk procedures including
      intubation, bronchoscopy, proning patients (which can lead to droplet production) and in some
      cases are reusing PPE, finding ways to reduce viral load or viral exposure are paramount.

      Povidone-iodine (PVP-I) is a broad-spectrum antiseptic with activity against bacteria, fungi,
      and viruses. It has been previously used in both intranasal preparations against MRSA as well
      as oral preparations in in-vitro studies of SARS-CoV-2, MERS-CoV, H1N1, and rotavirus with
      good efficacy.

      Due to the known breadth of its antiviral activity and similarities in molecular structure,
      it can be extrapolated that PVP-I should have robust activity against SARS-CoV-2. Eggers et
      al found that at a concentration of 1% there was a reduction of viral activity of 99.99% in
      in-vitro assays. At 2 minutes, a concentration of 0.23% was enough to reduce viral loads
      appreciably. New data has demonstrated efficacy in-vitro of PVP-I against SARS-CoV-2 at low
      concentrations.

      PVP-I is widely used as an antiseptic and is well-tolerated and has been shown to have little
      to no effect on mucociliary clearance, olfaction, or thyroid function if iodine holidays are
      taken, although care must be utilized in monitoring.

      In this study, front line healthcare workers will be asked to complete a pre-participation
      survey and screened for COVID positivity. They will then be given premade PVP-I gargles and
      nasal sprays, as well as a calendar card to mark compliance. PVP-I nasal spray and gargle
      (10% diluted 1:30) will be used prior to the start of a shift, during "lunch break", and at
      the end of shift. First, the nasal spray will be sprayed in the nose (2 sprays each naris).
      For adequate coverage, the participant should be able to taste the iodine or see it in the
      back of the throat. This should be left in place for 30 seconds. Then, the participant will
      gargle the solution for 30 seconds and not have anything to eat or drink by mouth for 30
      minutes. Treatment will continue for 3 weeks, or until the healthcare worker presents with
      COVID symptoms. Participants will then be tested for COVID positivity and asked to fill out a
      second questionnaire assessing study tolerability. At completion of the study, they will be
      asked to turn in their calendar card to assess how many applications they were able to
      complete.

      Given the high rate of asymptomatic carriers, a second arm will also be planned for patients
      who have a 7+ day hospitalization or who are set to undergo a significant surgical procedure.
      These patients will be offered participation in the study as well and will be given the same
      questionnaire and undergo preoperative testing if they consent. For patients in the study
      group, PVIP gargle and nasal sprays will be applied preoperatively or shortly after admission
      and enrollment in the study for the non-operative group. The patients will then be retested
      in 2 weeks or as directed by the presentation of symptoms concerning for infection with
      SARS-CoV-2.

      Community spread has been found to be the most likely implicated in infection and thus the
      trial is now being expanded to include community members. Thus, a THIRD arm has now been
      added to include community members. Prescreening questionnaires will be given. As long as the
      participant has had no prior history of a positive COVID-19 test, they will be considered
      eligible for participation. After a screening consultation, they will undergo a COVID-19 test
      (should be completed within 72 hours of screening). If negative, they will be eligible.
      Participants who are pregnant, breastfeeding, have thyroid disease or cancer, or who have an
      allergy to iodine/shellfish/or contrast dye can still participate but will automatically be
      on the control arm. Participants may opt to be on either the PVP-I arm or the control arm.
      They will be asked to fill out a daily questionnaire regarding their exposures and whether
      they were wearing a mask or if other people were wearing a mask at that time.
    

Intervention name(s): Povidone-Iodine Nasal Spray and Gargle; Povidone-Iodine Nasal Spray and Gargle; Povidone-Iodine Nasal Spray and Gargle
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Healthcare workers will receive standard PPE and a pre- and post-study nasal swab COVID19 test. Additionally, they will receive povidone-iodine nasal spray and gargle (10% diluted 1:30) to use at the beginning of their shift, in the middle, and at the end of their shift.; Patients will receive standard of care treatment and a pre- and post-study nasal spray COVID19 test. Additionally, they will receive povidone-iodine nasal spray and gargle shortly after admission or preoperatively.; Community members will receive a pre- and post-study nasal swab COVID19 test. Additionally, they will receive povidone-iodine nasal spray and gargle (10% diluted 1:30) to use at home.
Intervention MeSH terms: Iodine; Cadexomer iodine; Povidone-Iodine; Povidone
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: COVID-19; SARS-CoV 2; Health Care Workers; COVID-19 Prophylaxis