Malaysian COVID-19 Anosmia Study (Phase 2) - A Nationwide Multicentre Case-Control Study

• ClinicalTrials.gov Identifier: NCT04384042
• Recruitment Status: Not yet recruiting
• First Posted: May 12, 2020
• Last Update Posted: May 14, 2020
• Sponsor: Hospital Sultanah Bahiyah
• Collaborators: Hospital Tuanku Fauziah, Kangar, Perlis; Hospital Sultanah Maliha, Langkawi, Kedah; Penang Hospital, Malaysia; Hospital Raja Permaisuri Bainun; Hospital Sungai Buloh, Selangor; Kuala Lumpur General Hospital; Hospital Tuanku Jaafar, Seremban, Negeri Sembilan; Hospital Melaka, Melaka; Hospital Sultan Ismail, Johor Bahru, Johor; Hospital Permai, Johor Bahru, Johor; Hospital Sultanah Aminah Johor Bahru; Hospital Enche Besar Hajjah Khalsom, Kluang, Johor; Hospital Raja Perempuan Zainab II, Kota Bahru, Kelantan; Hospital Sultanah Nur Zahirah, Kuala Terengganu, Terengganu; Hospital Tengku Ampuan Afzan, Kuantan, Pahang; Sarawak General Hospital; Hospital Queen Elizabeth, Malaysia
• Information provided by (Responsible Party): Siti Sabzah bt Mohd Hashim, MD, MS (ORL-HNS), Hospital Sultanah Bahiyah

Tracking Information

• First Submitted Date: May 10, 2020
• First Posted Date: May 12, 2020
• Last Update Posted Date: May 14, 2020
• Estimated Study Start Date: May 2020
• Estimated Primary Completion Date: July 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 10, 2020)

• Presence or absence of olfactory and taste disturbances in study participants [ Time Frame: 2 weeks prior to answering questionnaire/ prior to diagnosis of COVID-19 infection ]
  In the patient-reported online questionnaire, subjects will be asked regarding whether they experienced symptoms of olfactory and/or taste disturbances
• Adjusted odds ratio of olfactory & taste disturbances in COVID-19 infection [ Time Frame: 2 weeks prior to answering questionnaire/ prior to diagnosis of COVID-19 infection ]
  The relationship between case & control status and each exposure variable will be estimated by odds ratios and their 95% confidence intervals using conditional logistic regression models.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 10, 2020)

• Clinical manifestations of study participants [ Time Frame: 2 weeks prior to answering questionnaire/ prior to diagnosis of COVID-19 infection ]
  In the patient-reported online questionnaire, subjects will be asked regarding other symptoms they experienced when they were diagnosed with COVID-19/within the past 2 weeks of answering the questionnaire (e.g. headache, nasal congestion, fever, chills, cough, dyspnoea, gastrointestinal symptoms, eye & ear symptoms)
• Other pre-existing health conditions [ Time Frame: Baseline ]
  In the patient-reported online questionnaire, subjects will be asked regarding their pre-existing health conditions (for example, obesity, diabetes, hypertension, cardiac conditions, previous head trauma, chronic rhinosinusitis, etc.)
• Positive predictive value (PPV) of olfactory and taste disturbances in predicting diagnosis of COVID-19 infection [ Time Frame: Baseline ]
  PPV reflects the probability that the presence of olfactory and taste disturbances will have a positive diagnosis of COVID-19. This is derived from dividing the number of patients with olfactory & taste disturbances with COVID-19 infection over the total number of patients with olfactory and taste disturbances, and multiplying by 100%
• Negative predictive value (NPV) of olfactory and taste disturbances in predicting absence of COVID-19 infection [ Time Frame: Baseline ]
  NPV reflects the probability that the absence of olfactory and taste disturbances will have a negative diagnosis of COVID-19. This is derived from dividing the number of patients without olfactory & taste disturbances and without COVID-19 infection over the total number of patients with no olfactory and taste disturbances, and multiplying by 100%
• Sensitivity of olfactory and taste disturbances in predicting COVID-19 infection [ Time Frame: Baseline ]
  The percentage of true positives, i.e. the proportion of patients with olfactory and taste disorders with COVID-19 infection. This can be calculated by dividing the number of subjects with olfactory & taste disturbances who have COVID-19 infection with the number of patients with olfactory & taste disturbances, and multiplying by 100%
• Specificity of olfactory and taste disturbances in predicting COVID-19 infection [ Time Frame: Baseline ]
  The percentage of true negatives, i.e. the proportion of patients without olfactory and taste disorders who do not have COVID-19 infection. This can be calculated by dividing the number of subjects without olfactory & taste disturbances who do not have COVID-19 infection with the number of patients without olfactory & taste disturbances, and multiplying by 100%

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Malaysian COVID-19 Anosmia Study (Phase 2) - A Nationwide Multicentre Case-Control Study
• Official Title: Olfactory and Gustatory Disturbances as a Clinical Presentation of Coronavirus Disease 2019 (COVID-19) Infection in Malaysia - A Nationwide Multicentre Case-Control Study

Brief Summary

The Malaysian COVID-19 Anosmia Study is a nationwide multicentre observational study to investigate the prevalence and characteristics of olfactory and gustatory/taste disturbances in COVID-19 infection in Malaysia, and to evaluate the predictive value of screening for these symptoms in COVID-19 infection.

This study consists of two phases: the first phase is a cross-sectional study and the second phase is a case-control study. The case-control study is described here (the cross-sectional study is described in a separate ClinicalTrials.gov record).

Detailed Description

The world is currently in the midst of the Coronavirus 2019 (COVID-19) pandemic that is caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). According to published cohort studies on COVID-29 infected patients, the most prevalent symptoms consist of fever, dry cough, dyspnoea, sputum production, myalgia, arthralgia, headache, diarrhoea, and sore throat. Recently, there have been concerns of significant viral transmission through asymptomatic, pre-symptomatic or even mildly symptomatic patients.

There is increasing anecdotal evidence from patients and healthcare professionals highlighting isolated loss of sense of smell (anosmia) and taste disturbances (dysgeusia) as atypical symptoms of COVID-19 infection in otherwise asymptomatic patients. In parallel, expert statements from the British Association of Otorhinolaryngology-Head & Neck Surgery (ENT UK), British Rhinological Society, and the American Association of Otolaryngology-Head & Neck Surgery (AAO-HNS) have suggested that olfactory and taste disturbances could be a clinical feature of COVID-19 infection.

Rapidly emerging evidence from Europe, the United Kingdom and the United States have found olfactory and taste disturbances to be highly prevalent in patients diagnosed with COVID-19. In contrast, there is currently limited evidence from Asia on the prevalence of these symptoms in COVID-19 infection. Additionally, there is also limited evidence on the predictive value of screening for olfactory and taste disturbance in COVID-19 patients with subclinical symptoms.

The aim of this case-control study is to study the predictive value of screening for olfactory and taste disturbance in patients with COVID-19 infection in Malaysia. The cases will be selected from the cohort of COVID-19 positive patients recruited from participating Malaysian Ministry of Health-designated COVID-19 treating hospitals across the country (from Phase 1 of the Malaysian COVID-19 Anosmia Study). Controls will be recruited from healthy volunteers who will will answer the an online questionnaire to evaluate and characterise their olfactory and taste symptoms. This is the same questionnaire that is answered by the COVID-19 patients in case cohort.

• Study Type: Observational
• Study Design: Observational Model: Case-Control; Time Perspective: Retrospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Probability Sample

Study Population

This study population will draw subjects from the cohort in Phase 1 of the Malaysian COVID-19 Anosmia Study (Nationwide Multicentre Cross-Sectional Study) as cases. These cases will comprise adult patients with laboratory-confirmed COVID-19 infection from participating Malaysian hospital sites in this study, since the arrival of COVID-19 infection in Malaysia (January 2020) until present time.

The control subjects will be age and sex-matched healthy volunteers recruited from participating hospital sites in this study.

Condition

• SARS-CoV Infection
• COVID-19
• Anosmia
• Dysgeusia

Intervention

Other: Patient-Reported Online Questionnaire on Olfactory & Taste Disturbances

This is an online patient-reported questionnaire that examines the presence or absence of olfactory and taste disturbances, the onset of olfactory and taste disturbances in relation to other COVID-19 symptoms, and the temporal evolution of the severity of olfactory and taste disturbances. The occurrence of ear symptoms in COVID-19 infection will also be evaluated in this questionnaire as a secondary outcome. The questionnaire will also have questions relating to the patient's underlying health conditions, risk factors for COVID-19 infection, and demographics.

Study Groups/Cohorts

• Malaysian COVID-19 Cohort (Cases)
  A cohort of COVID-19 positive patients will be recruited from participating Malaysian Ministry of Health-designated COVID-19 treating hospitals across the country.
  Intervention: Other: Patient-Reported Online Questionnaire on Olfactory & Taste Disturbances
• Healthy Volunteers (Controls)
  A cohort of age and sex-matched healthy volunteers will be recruited from participating Malaysian Ministry of Health-designated COVID-19 treating hospitals across the country.
  Intervention: Other: Patient-Reported Online Questionnaire on Olfactory & Taste Disturbances

Publications *

• Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24. Erratum in: Lancet. 2020 Jan 30;:.
• Giacomelli A, Pezzati L, Conti F, Bernacchia D, Siano M, Oreni L, Rusconi S, Gervasoni C, Ridolfo AL, Rizzardini G, Antinori S, Galli M. Self-reported Olfactory and Taste Disorders in Patients With Severe Acute Respiratory Coronavirus 2 Infection: A Cross-sectional Study. Clin Infect Dis. 2020 Jul 28;71(15):889-890. doi: 10.1093/cid/ciaa330.
• Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, Chang J, Hong C, Zhou Y, Wang D, Miao X, Li Y, Hu B. Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China. JAMA Neurol. 2020 Jun 1;77(6):683-690. doi: 10.1001/jamaneurol.2020.1127.
• Lechien JR, Chiesa-Estomba CM, De Siati DR, Horoi M, Le Bon SD, Rodriguez A, Dequanter D, Blecic S, El Afia F, Distinguin L, Chekkoury-Idrissi Y, Hans S, Delgado IL, Calvo-Henriquez C, Lavigne P, Falanga C, Barillari MR, Cammaroto G, Khalife M, Leich P, Souchay C, Rossi C, Journe F, Hsieh J, Edjlali M, Carlier R, Ris L, Lovato A, De Filippis C, Coppee F, Fakhry N, Ayad T, Saussez S. Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study. Eur Arch Otorhinolaryngol. 2020 Aug;277(8):2251-2261. doi: 10.1007/s00405-020-05965-1. Epub 2020 Apr 6.
• Kaye R, Chang CWD, Kazahaya K, Brereton J, Denneny JC 3rd. COVID-19 Anosmia Reporting Tool: Initial Findings. Otolaryngol Head Neck Surg. 2020 Jul;163(1):132-134. doi: 10.1177/0194599820922992. Epub 2020 Apr 28. Review.
• Yan CH, Faraji F, Prajapati DP, Boone CE, DeConde AS. Association of chemosensory dysfunction and COVID-19 in patients presenting with influenza-like symptoms. Int Forum Allergy Rhinol. 2020 Jul;10(7):806-813. doi: 10.1002/alr.22579. Epub 2020 Jun 1.
• Spinato G, Fabbris C, Polesel J, Cazzador D, Borsetto D, Hopkins C, Boscolo-Rizzo P. Alterations in Smell or Taste in Mildly Symptomatic Outpatients With SARS-CoV-2 Infection. JAMA. 2020 May 26;323(20):2089-2090. doi: 10.1001/jama.2020.6771.

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: May 10, 2020): 60
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 2020
• Estimated Primary Completion Date: July 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Age at least 18 years old
2. For Cases: Laboratory confirmed COVID-19 infection [Reverse Transcription Polymerase Chain Reaction (RT-PCR)]
3. Patients clinically able to answer the questionnaire

Exclusion Criteria:

1. Patients with olfactory or taste/gustatory disorders before the COVID-19 epidemic
2. For Cases: Patients without a laboratory-confirmed COVID-19 diagnosis
3. For Cases: Patients in intensive care unit at the time of study

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Siti Sabzah Mohd Hashim, MD MS; +604 740 7335; dr_ctsabzah@yahoo.com

Contact: Shen-Han Lee, MB PhD MRCS; +6016 474 0088; shen-han.lee@cantab.net

• Listed Location Countries: Malaysia

Administrative Information

• NCT Number: NCT04384042
• Other Study ID Numbers: MCO-002
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Siti Sabzah bt Mohd Hashim, MD, MS (ORL-HNS), Hospital Sultanah Bahiyah
• Study Sponsor: Hospital Sultanah Bahiyah

Collaborators

• Hospital Tuanku Fauziah, Kangar, Perlis
• Hospital Sultanah Maliha, Langkawi, Kedah
• Penang Hospital, Malaysia
• Hospital Raja Permaisuri Bainun
• Hospital Sungai Buloh, Selangor
• Kuala Lumpur General Hospital
• Hospital Tuanku Jaafar, Seremban, Negeri Sembilan
• Hospital Melaka, Melaka
• Hospital Sultan Ismail, Johor Bahru, Johor
• Hospital Permai, Johor Bahru, Johor
• Hospital Sultanah Aminah Johor Bahru
• Hospital Enche Besar Hajjah Khalsom, Kluang, Johor
• Hospital Raja Perempuan Zainab II, Kota Bahru, Kelantan
• Hospital Sultanah Nur Zahirah, Kuala Terengganu, Terengganu
• Hospital Tengku Ampuan Afzan, Kuantan, Pahang
• Sarawak General Hospital
• Hospital Queen Elizabeth, Malaysia

Investigators

• Study Chair: Siti Sabzah Mohd Hashim, MD MS; Hospital Sultanah Bahiyah

• PRS Account: Hospital Sultanah Bahiyah
• Verification Date: May 2020