Povidone-Iodine Vs Essential Oil Vs Tap Water Gargling For COVID-19 Patients (GARGLES)

• ClinicalTrials.gov Identifier: NCT04410159
• Recruitment Status: Completed
• First Posted: June 1, 2020
• Results First Posted: July 21, 2020
• Last Update Posted: July 21, 2020
• Sponsor: Universiti Sains Islam Malaysia
• Collaborator: Universiti Kebangsaan Malaysia Medical Centre
• Information provided by (Responsible Party): NURUL AZMAWATI MOHAMED, Universiti Sains Islam Malaysia

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: COVID-19
• Interventions: Drug: Povidone-Iodine; Drug: Essential oils; Other: Tap water
• Enrollment: 20

Participant Flow

Recruitment Details	All patients were recruited 2 to 3 days after date of diagnosis (nasophryngeal swab postive for SARS-C0V-2. All patients were asymptomatic and admitted to the hospital for observation
Pre-assignment Details	No significant event occurred after enrollment

Arm/Group Title	Povidone-iodine	Essential Oils	Tap Water	Control
Arm/Group Description	gargle with povidone-iodine 10mL, 30 seconds, 3 times per day, 7 days Povidone-Iodine: Gargle	gargle with essential oils 20mL, 30 seconds, 3 times per day, 7 days Essential oils: Gargle	gargle with tap water 100 mL, 30 seconds, 3 times per day, 7 days Tap water: Gargle	This group will receive the standard treatment protocol without any additional intervention
Period Title: Overall Study
Started	5	5	5	5
Completed	5	5	5	5
Not Completed	0	0	0	0

Baseline Characteristics

Arm/Group Title		Povidone-iodine	Essential Oils	Tap Water	Control	Total
Arm/Group Description		gargle with povidone-iodine 10mL, 30 seconds, 3 times per day, 7 days Povidone-Iodine: Gargle	gargle with essential oils 20mL, 30 seconds, 3 times per day, 7 days Essential oils: Gargle	gargle with tap water 100 mL, 30 seconds, 3 times per day, 7 days Tap water: Gargle	This group received the standard treatment protocol without any additional intervention	Total of all reporting groups
Overall Number of Baseline Participants		5	5	5	5	20
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	5 participants	5 participants	5 participants	5 participants	20 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	5 100.0%	5 100.0%	5 100.0%	5 100.0%	20 100.0%
	>=65 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	5 participants	5 participants	5 participants	5 participants	20 participants
		32.4 (7.44)	34.4 (12.50)	30.8 (3.77)	24.8 (2.68)	30.6 (7.91)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	5 participants	5 participants	5 participants	5 participants	20 participants
	Female	3 60.0%	1 20.0%	0 0.0%	0 0.0%	4 20.0%
	Male	2 40.0%	4 80.0%	5 100.0%	5 100.0%	16 80.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	5 participants	5 participants	5 participants	5 participants	20 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Asian	5 100.0%	5 100.0%	5 100.0%	5 100.0%	20 100.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	White	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	More than one race	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
Malaysia	Number Analyzed	5 participants	5 participants	5 participants	5 participants	20 participants
		5	5	5	5	20

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Early Viral Clearance
Description	Viral clearance is defined as two negative RT-PCR (of swabs from oropharynx and nasopharynx) results at least 24 hours apart
Time Frame	Day 6

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Povidone-iodine	Essential Oils	Tap Water	Control
Arm/Group Description:	gargle with povidone-iodine 10mL, 30 seconds, 3 times per day, 7 days Povidone-Iodine: Gargle	gargle with essential oils 20mL, 30 seconds, 3 times per day, 7 days Essential oils: Gargle	gargle with tap water 100 mL, 30 seconds, 3 times per day, 7 days Tap water: Gargle	This group will receive the standard treatment protocol without any additional intervention
Overall Number of Participants Analyzed	5	5	5	5
Measure Type: Count of Participants; Unit of Measure: Participants
	5 100.0%	4 80.0%	1 20.0%	0 0.0%

2. Secondary Outcome

Title	Number of Participants With Negative RT-PCR Results
Description	RT-PCR (swabs from oropharynx and nasopharynx) taken at day 12
Time Frame	Day 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Povidone-iodine	Essential Oils	Tap Water	Control
Arm/Group Description:	gargle with povidone-iodine 10mL, 30 seconds, 3 times per day, 7 days Povidone-Iodine: Gargle	gargle with essential oils 20mL, 30 seconds, 3 times per day, 7 days Essential oils: Gargle	gargle with tap water 100 mL, 30 seconds, 3 times per day, 7 days Tap water: Gargle	This group will receive the standard treatment protocol without any additional intervention
Overall Number of Participants Analyzed	5	5	5	5
Measure Type: Count of Participants; Unit of Measure: Participants
	5 100.0%	4 80.0%	2 40.0%	1 20.0%

3. Secondary Outcome

Title	Number of Patients That Progress to More Severe Disease
Description	Presence of signs and symptoms of more severe COVID19 Based symptoms diary and clinical evaluation
Time Frame	Day 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Povidone-iodine	Essential Oils	Tap Water	Control
Arm/Group Description:	gargle with povidone-iodine 10mL, 30 seconds, 3 times per day, 7 days Povidone-Iodine: Gargle	gargle with essential oils 20mL, 30 seconds, 3 times per day, 7 days Essential oils: Gargle	gargle with tap water 100 mL, 30 seconds, 3 times per day, 7 days Tap water: Gargle	This group will receive the standard treatment protocol without any additional intervention
Overall Number of Participants Analyzed	5	5	5	5
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	0 0.0%	0 0.0%	0 0.0%

4. Secondary Outcome

Title	Number of Patients With Abnormal Radiological Findings
Description	abnormal chest x-ray or CT scan
Time Frame	Day 0-14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Povidone-iodine	Essential Oils	Tap Water	Control
Arm/Group Description:	gargle with povidone-iodine 10mL, 30 seconds, 3 times per day, 7 days Povidone-Iodine: Gargle	gargle with essential oils 20mL, 30 seconds, 3 times per day, 7 days Essential oils: Gargle	gargle with tap water 100 mL, 30 seconds, 3 times per day, 7 days Tap water: Gargle	This group will receive the standard treatment protocol without any additional intervention
Overall Number of Participants Analyzed	5	5	5	5
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	0 0.0%	0 0.0%	0 0.0%

5. Secondary Outcome

Title	Number of Patients With Abnormal Laboratory Findings
Description	Abnormal absolute lymphocytic count Abnormal C-reactive protein
Time Frame	Day 0-14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Povidone-iodine	Essential Oils	Tap Water	Control
Arm/Group Description:	gargle with povidone-iodine 10mL, 30 seconds, 3 times per day, 7 days Povidone-Iodine: Gargle	gargle with essential oils 20mL, 30 seconds, 3 times per day, 7 days Essential oils: Gargle	gargle with tap water 100 mL, 30 seconds, 3 times per day, 7 days Tap water: Gargle	This group will receive the standard treatment protocol without any additional intervention
Overall Number of Participants Analyzed	5	5	5	5
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	0 0.0%	0 0.0%	0 0.0%

Adverse Events

Time Frame	Adverse event data were collected from day 1 of intervention until day 14
Adverse Event Reporting Description	Similar to clinicaltrial.gov
Arm/Group Title	Povidone-iodine	Essential Oils	Tap Water	Control
Arm/Group Description	gargle with povidone-iodine 10mL, 30 seconds, 3 times per day, 7 days Povidone-Iodine: Gargle	gargle with essential oils 20mL, 30 seconds, 3 times per day, 7 days Essential oils: Gargle	gargle with tap water 100 mL, 30 seconds, 3 times per day, 7 days Tap water: Gargle	This group will receive the standard treatment protocol without any additional intervention
All-Cause Mortality
	Povidone-iodine	Essential Oils	Tap Water	Control
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/5 (0.00%)	0/5 (0.00%)	0/5 (0.00%)	0/5 (0.00%)
Serious Adverse Events
	Povidone-iodine	Essential Oils	Tap Water	Control
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/5 (0.00%)	0/5 (0.00%)	0/5 (0.00%)	0/5 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Povidone-iodine	Essential Oils	Tap Water	Control
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/5 (0.00%)	0/5 (0.00%)	0/5 (0.00%)	0/5 (0.00%)

Limitations and Caveats

Inadequate budget for laboratory test lead to small numbers of subjects analyzed

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: NURUL AZMAWATI MOHAMED
• Organization: UNIVERSITI SAINS ISLAM MALAYSIA
• Phone: +603 42892400 ext 2417
• EMail: drnurul@usim.edu.my

Publications:

Eggers M, Koburger-Janssen T, Eickmann M, Zorn J. In Vitro Bactericidal and Virucidal Efficacy of Povidone-Iodine Gargle/Mouthwash Against Respiratory and Oral Tract Pathogens. Infect Dis Ther. 2018 Jun;7(2):249-259. doi: 10.1007/s40121-018-0200-7. Epub 2018 Apr 9.

Eggers M. Infectious Disease Management and Control with Povidone Iodine. Infect Dis Ther. 2019 Dec;8(4):581-593. doi: 10.1007/s40121-019-00260-x. Epub 2019 Aug 14. Erratum In: Infect Dis Ther. 2019 Aug 22;:

Dennison DK, Meredith GM, Shillitoe EJ, Caffesse RG. The antiviral spectrum of Listerine antiseptic. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1995 Apr;79(4):442-8. doi: 10.1016/s1079-2104(05)80124-6.

Satomura K, Kitamura T, Kawamura T, Shimbo T, Watanabe M, Kamei M, Takano Y, Tamakoshi A; Great Cold Investigators-I. Prevention of upper respiratory tract infections by gargling: a randomized trial. Am J Prev Med. 2005 Nov;29(4):302-7. doi: 10.1016/j.amepre.2005.06.013.

• Responsible Party: NURUL AZMAWATI MOHAMED, Universiti Sains Islam Malaysia
• ClinicalTrials.gov Identifier: NCT04410159
• Other Study ID Numbers: USIMalaysia
• First Submitted: May 27, 2020
• First Posted: June 1, 2020
• Results First Submitted: July 8, 2020
• Results First Posted: July 21, 2020
• Last Update Posted: July 21, 2020