Eucalyptus Oil as Adjuvant Therapy for Coronavirus Disease 19 (COVID-19)
Condition: COVID-19
MeSH terms: COVID-19
Study type: Interventional
Phase: Phase 2

Summary: 
      Background :

      Based on several clinical trials, eucalyptus oil can suppress edema formation and reduce
      inflammation, where the effect of 1,8-cineole is due to the inhibition of cytokine secretion
      by T lymphocytes. This but not limited to the reduction of interleukin (IL) of IL-4, IL-5,
      and IL-10 in nasal lavage fluids and levels of IL- 1β, IL-6, Tumor Necrosis Factor-α (TNF-α),
      and Interferon-γ (IFN-γ) in lung tissue of mice infected with influenza virus. Hence the
      researchers assume that Eucalyptus may possess benefits in COVID-19 as adjuvant therapy.

      Objectives :

      The primary objective of this study is to evaluate the efficacy of Eucalyptus oil as adjuvant
      therapy in mild-moderate COVID-19 patients.

      Hypothesis :

      Eucalyptus oil may reduce the inflammatory cytokines which eventually improves clinical
      symptoms
    

Detailed description: 
      Detailed Objectives :

        1. To assess the safety of Eucalyptus oil as an adjuvant to the standard of care in
           treating patients with mild to moderate COVID-19 symptoms.

        2. To document the effect of Eucalyptus oil on clinical symptoms improvement, including
           cough, anosmia, and sore throat.

        3. To assess the effect of Eucalyptus oil on viral load indirectly reflected by the Real
           Time-Polymerase Chain Reaction/RT-PCR cycle threshold (CT)

        4. To assess the effect of Eucalyptus oil on NLR, Interleukin-6, Interleukin-10, and Tumor
           Growth Factor-β (TGF-β) as inflammatory marker

        5. To assess the effect of Eucalyptus oil on immunoglobulin (Ig) M and G in patient's serum

      Target population:

      Patients with mild-moderate COVID-19

      Setting:

      Hospital and outpatient care

      Intervention:

      External use of Eucalyptus oil

      Subject Recruitment and Screening :

        1. A written, signed, and dated (ICF) consent form will be obtained from the patient before
           the study's inclusion. Assessment and records of patient's clinical report forms
           including demographic data, comorbidities and concurrent medications, symptoms
           experienced by the patient, body weight, height of the body, body mass index, vital
           signs, and fingertip oxygen saturation.

        2. Baseline laboratory tests including complete blood count (CBC), neutrophil-lymphocyte
           ratio (NLR), liver (alanine aminotransferase (ALT), aspartate aminotransferase (AST),
           kidney function tests (serum creatinine), serum ferritin, blood glucose, coagulation
           test (prothrombin time and activated partial thromboplastin time), cytokine level (IL-6,
           IL-10, and TGF-β) will be assessed. On admission, computed tomography (CT) scan of the
           chest will also be performed.

      Detailed procedures :

      Eucalyptus oil will be applied to the surgery mask, 4 times a day, which is 45 minutes
      duration in each session for 14 days. Clinical assessment and vital signs, and follow-up
      RT-PCR tests by nasopharyngeal swab will be documented on days 5, 10, and 15. Follow-up
      laboratory results for blood, liver function, kidney function, blood glucose, cytokine level,
      and CT scan will be performed on Day 15. If moderate COVID-19 patients confirmed negative
      RT-PCR test results in 2 consecutive tests, the patient is allowed to be discharged and
      continue their adjuvant treatment at home (in the intervention group).

      Sample size estimation :

      following the sample size estimation of two different means

        1. Type 1 error 5%

        2. Power of study 80%

        3. superiority trial hypothesis

        4. equal allocation for two arms

      f. effect size is estimated at 0.7 total sample required : 52

      Statistical Analysis

        1. Intention to treat

        2. Descriptive statistic

        3. Repeated measurement analysis using mixed model analysis.
    

Intervention name(s): Eucalyptus Oil; Standard COVID medication
Intervention type(s): Drug; Drug
Intervention description(s): The Eucalyptus Oil pack contains Oleum Eucalyptus citriodora, Oleum Eucalyptus globulus, and Peppermint oil, given 4 times daily for 45 minutes each frequency, applied to the mask.; This standard treatment is personalized according to the severity but is not limited to standard antiviral therapy, azithromycin 500 mg a day, vitamin C 500 mg 8 hourly a day, zinc 20 mg a day, tablet of complex vitamin B, and other symptomatic treatments.
Other intervention name(s): Herbal Roll On; COVID Medication
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Patients will be randomized into 2 study groups before starting their medication. The first group was only given standard COVID-19 therapy. While the treated group will be given standard COVID-19 along with adjuvant therapy (Eucalyptus oil on external use)
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: COVID-19; Eucalyptus; Viral Clearance; Cytokine Level; Clinical Improvement