COVID-19: SARS-CoV-2 Detection in Saliva, Oropharyngeal and Nasopharyngeal Specimens

• ClinicalTrials.gov Identifier: NCT04715607
• Recruitment Status: Recruiting
• First Posted: January 20, 2021
• Last Update Posted: March 10, 2021
• Sponsor: Rigshospitalet, Denmark
• Collaborators: Hvidovre University Hospital; Region Hovedstadens Apotek
• Information provided by (Responsible Party): Tobias Todsen, Rigshospitalet, Denmark

Study Description

Brief Summary:

The aim of this study is to compare the SARS-CoV-2 detection rate using either a Saliva, oropharyngeal swabs or nasopharyngeal swab method for specimen collection.

Condition or disease	Intervention/treatment	Phase
SARS-CoV Infection; Covid19; Coronavirus	Diagnostic Test: Sequence of testing.	Not Applicable

Detailed Description:

The reference test to evaluate patients with suspected respiratory infection caused by virus is a real-time reverse transcription-polymerase chain reaction (RT-PCR) from a nasopharyngeal swab (NPS). However, other specimen collection methods like oropharyngeal swabs (OPS) and a saliva specimen collection have also been accepted by the Centers for Disease Control and Prevention for SARS-CoV-2 testing during the current coronavirus disease 19 (COVID-19) pandemic. It is unclear how much the SARS-CoV-2 detection rate differs when using different sampling methods and the aim of this study is to compare the expected COVID-19 detection rate using saliva, oropharyngeal swabs or nasopharyngeal swab in a public setting.

We, therefore, aim to investigate the detection rate of SARS-CoV-2 in Saliva, oropharyngeal swab, and nasopharyngeal swab specimen samples collected in symptomatic and non-symptomatic individuals tested for COVID-19 in a public test center during the COVID-19 pandemic.

Individuals referred for outpatient COVID-19 testing center will be invited to participate in a prospective clinical study. They will have saliva, OPS, and NPS specimen collection performed at the same time and analyzed separately for SARS-CoV-2. The rate for SARS-CoV-2 detection in saliva, OPS, and NPS will be compared using a logistic regression mixed-effect analysis. A Sample Size Calculation estimated that a sample of 18,000 participants would be needed for the trial with 80% power at a significance level of 5%.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 22000 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: All participants will have Saliva collected and recieve nasopharyngeal swabs and oropharyngeal swabs for SARS-COV2. To avoid systematic bias we plan to randomize the sequence of testing.
• Masking: Double (Investigator, Outcomes Assessor)
• Primary Purpose: Diagnostic
• Official Title: Comparison of Detection Rate of SARS-CoV-2 in Saliva, Oropharyngeal and Nasopharyngeal Specimens in a Public COVID-19 Test Setting
• Actual Study Start Date: January 22, 2021
• Estimated Primary Completion Date: May 5, 2021
• Estimated Study Completion Date: May 30, 2021

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Nasopharyngeal swab, oropharyngeal swab, and salvia collection; The participants will first be tested with nasopharyngeal swabs followed by oropharyngeal swab and saliva collection. The collection material, virus transport medium and laboratory equipment for each method is the same in both arms	Diagnostic Test: Sequence of testing.; The participants will be tested in the following sequences of sampling technique: (1) nasopharyngeal swab, oropharyngeal swab, and salvia collection OR (2) oropharyngeal swab, salvia collection, and nasopharyngeal swab OR (3) salvia collection, nasopharyngeal swab, and oropharyngeal swab. Only the sequence is different in the different arm, while the sampling technique for each method is the same in all arms.
Active Comparator: Oropharyngeal swab, salvia collection, and nasopharyngeal swab; The participants will first be tested with oropharyngeal swabs followed by saliva collection and nasopharyngeal swab. The collection material, virus transport medium and laboratory equipment for each method is the same in both arms	Diagnostic Test: Sequence of testing.; The participants will be tested in the following sequences of sampling technique: (1) nasopharyngeal swab, oropharyngeal swab, and salvia collection OR (2) oropharyngeal swab, salvia collection, and nasopharyngeal swab OR (3) salvia collection, nasopharyngeal swab, and oropharyngeal swab. Only the sequence is different in the different arm, while the sampling technique for each method is the same in all arms.
Active Comparator: Salvia collection, nasopharyngeal swab, and oropharyngeal swab; The participants will first be tested with saliva collection followed by nasopharyngeal swab and oropharyngeal swabs. The collection material, virus transport medium and laboratory equipment for each method is the same in both arms	Diagnostic Test: Sequence of testing.; The participants will be tested in the following sequences of sampling technique: (1) nasopharyngeal swab, oropharyngeal swab, and salvia collection OR (2) oropharyngeal swab, salvia collection, and nasopharyngeal swab OR (3) salvia collection, nasopharyngeal swab, and oropharyngeal swab. Only the sequence is different in the different arm, while the sampling technique for each method is the same in all arms.

Outcome Measures

Primary Outcome Measures :

1. SARS-CoV-2 detection rates for oropharyngeal swabs (OPS) compared with nasopharyngeal swabs and saliva collection. [ Time Frame: 48 hours after testing ]
   Due to the high specificity of RT-PCR, we will define a participant with an RT-PCR positive result from either Saliva, OPS or NPS as having a COVID-19 infection. The combined Saliva/OPS/NPS result will therefore be used as the diagnostic reference standard to calculate the sensitivity for the Saliva, OPS and NPS tests.

Secondary Outcome Measures :

1. SARS-CoV-2 RT-PCR cycle threshold (Ct) values [ Time Frame: 48 hours after testing ]
   Ct values are compared between testing methods
2. OPS, NPS and saliva test discomfort and likelihood to get retested [ Time Frame: immediately after testing (10 minutes) ]
   Discomfort scores (1-10) and likelihood to get retested are compared between testing methods
3. Ratio of mutations in SARS-CoV-2 [ Time Frame: 48 hours after testing ]
   Detection rate of any mutations in SARS-CoV-2

Eligibility Criteria

• Ages Eligible for Study: 16 Years to 120 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Gender Based Eligibility: Yes
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• volunteers, who are attending the COVID-19 test facilities to obtain a RT-PCR test.
• oral and written informed consent to participate before entering the study.

Exclusion Criteria:

• Failure to understand and provide informed consent.
• Neck breathers (tracheostomy/laryngectomy patients) or other nasopharyngeal or oropharyngeal anomalies that do not allow for sampling using swabs.

Contacts and Locations

Contacts

Contact: Tobias Todsen, MD, PhD; 00 45 3545 6033; Tobias.todsen@regionh.dk

Locations

Denmark

Valby COVID-19 teststed; Recruiting

Copenhagen, Valby, Denmark, 2500

Contact: Tobias Gredal

Sponsors and Collaborators

Rigshospitalet, Denmark

Hvidovre University Hospital

Region Hovedstadens Apotek

Investigators

• Principal Investigator: Tobias Todsen, MD, PhD; Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet
• Study Director: Nikolai Kirkby, MD, PhD; Department of Clinical Microbiology, Rigshospitalet

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Todsen T, Tolsgaard M, Folke F, Jakobsen KK, Ersbøll AK, Benfield T, von Buchwald C, Kirkby N. SARS-CoV-2 in saliva, oropharyngeal and nasopharyngeal specimens. Dan Med J. 2021 Apr 7;68(5). pii: A01210087.

• Responsible Party: Tobias Todsen, MD, PhD, Assistant professor Tobias Todsen, Rigshospitalet, Denmark
• ClinicalTrials.gov Identifier: NCT04715607
• Other Study ID Numbers: 2021-01
• First Posted: January 20, 2021
• Last Update Posted: March 10, 2021
• Last Verified: January 2021

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

Additional relevant MeSH terms:

Severe Acute Respiratory Syndrome; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases