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A double-blind placebo controlled randomized parallel-group phase 1-2 proof-of-concept clinical trial on efficacy and safety of Sri Weera Badhra Dhamma Prathishakthi Jeewa Panaya© for asymptomatic patients or patients with mild to moderate COVID-19.

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SLCTR Registration Number

SLCTR/2021/001


Date of Registration

05 Jan 2021

The date of last modification

Jan 05, 2021



Application Summary


Scientific Title of Trial

A double-blind placebo controlled randomized parallel-group phase 1-2 proof-of-concept clinical trial on efficacy and safety of Sri Weera Badhra Dhamma Prathishakthi Jeewa Panaya© for asymptomatic patients or patients with mild to moderate COVID-19.


Public Title of Trial

Randomized double-blind placebo controlled parallel-group phase 1-2 proof-of-concept clinical trial of the herbal preparation Sri Weera Badhra Dhamma Prathishakthi Jeewa Panaya© for patients with asymptomatic or with mild to moderate COVID-19.


Disease or Health Condition(s) Studied

COVID-19, SARS-COV-2 infection


Scientific Acronym

TEAM-COVID (Trial for Efficacy of Alternative Medicine in COVID)


Public Acronym

TEAM-COVID (Trial for Efficacy of Alternative Medicine in COVID)


Brief title

Trial for Efficacy of Alternative Medicine in COVID


Universal Trial Number

U1111-1262-3889


Any other number(s) assigned to the trial and issuing authority

ERC/2020/80-R (ERC, Faculty of Medical and Allied Health Sciences, Rajarata University of Sri Lanka)


Trial Details


What is the research question being addressed?

Is Sri Weera Badhra Dhamma Prathishakthi Jeewa Panaya©, a herbal preparation safe and efficacious comparted to placebo in reducing the viral load of patients with COVID-19 who are asymptomatic or have mild to moderate disease?


Type of study

Interventional


Study design

Allocation

Randomized controlled trial


Masking

Double blinded : Investigators, Data analysts, Healthcare providers, Outcome assessors


Control

Placebo


Assignment

Parallel


Purpose

Treatment


Study Phase

Phase 1-2


Intervention(s) planned

Study setting(s): Methsirisewana (affiliated to Teaching Hospital, Anuradhapura) and Nochchiyagama Divisional Hospital (A) –both dedicated COVID-19 treatment centers, Sri Lanka

Method of randomization: Participants will be randomized in groups of four (blocked randomization) using WINPEPI software following antibody negative and cycle threshold value of less than 38 in quantitative reverse transcription PCR (RT-qPCR). Randomization will be done blocks of 4 separately at the two trial sites. The combination of the blocks may be anyone of the following: TTCC (T for treatment, C for control), TCTC, TCCT, CTTC, CTCT, CCTT. A total of 32 blocks will be randomly generated.

Allocation concealment will be ensured by the use of sequentially numbered, opaque, sealed envelopes and the randomization code will not be released until the patient has been recruited into the trial. Block identity and sequence within each block will not be known to the treatment allocation team

Intervention: The interventional product is the Sri Weera Badhra Dhamma Prathishakthi Jeewa Panaya©, a novel herbal preparation. The formulation is a proprietary product containing bees honey, pericarp and mace of nutmeg (Myristica fragrans,), fennel seeds in powdered form (Foeniculum vulgare) and juice of raw ginger rhizomes (Zingiber officinale). The entire process of preparation was done under the supervision of an expert committee of Ayurveda physicians in accordance with the standard practices of Ayurveda drug manufacturing. The interventional arm will receive the interventional product 15 ml, orally, twice daily (12 hours apart) for 3 days. The first dose will be after the 2nd RT-qPCR and antibody test

Control: The control arm will receive an identical matched placebo to be taken 15ml, orally, twice daily (12 hours apart) for 3 days. The placebo will contain coconut treacle (©KIST). The interventional product and the placebo will be packed and a sealed in bottles with the printed logo at the Ayurvedic Drug Corporation and labelled A & B. Both treatment and placebo syrups in individual doses (15ml) will be packed in identical bottles, wrapped in the same cover, and packed in identical boxes.

Standard Treatment: The standard therapy will be provided to participants of both arms would be according to the Ministry of Health Guidelines (Ministry of Health Sri Lanka. Guidance for treating patients with COVID -19 infection in Sri Lanka_02.12.2020. 2020. p. 9. Ministry of Health Sri Lanka. Provisional Clinical Practice Guidelines on COVID-19 suspected and confirmed patients, 2020).

Blinding: Healthcare providers, Outcome assessors and Data analysts will be blinded to the interventional status. Patients will not be blinded as the interventional product and the control have a different taste.


Inclusion criteria

  1. All consenting male and female adults (18–80 years of age)
  2. Asymptomatic or mild or moderate disease (as defined in the case definition)
  3. Two positive RT-qPCR tests
  4. Negative antibody test
  5. Cycle threshold (Ct) value <38 at the time of recruitment

Case definition: US Department of Health and Human Services, Food and Drug Administration, Centre for Drug Evaluation and Research, Centre for Biologics Evaluation and Research. COVID-19: Developing Drugs and Biological Products for Treatment or Prevention Guidance for Industry. 2020;(May):1–11.


Exclusion criteria

  1. Pregnant (known pregnancy or positive urine strip test) and lactating females
  2. Patients who have ingested Sri Weera Badhra Dhamma Prathishakthi Jeewa Panaya© within the past six weeks
  3. Patients with known allergy to the individual ingredients (Bees honey, nutmeg, fennel, raw ginger) of Sri Weera Badhra Dhamma Prathishakthi Jeewa Panaya©
  4. Any diagnosed co-morbidity such as diabetes, hypertension, renal disease, liver disease or bronchial asthma.


Primary outcome(s)

1.

The Cycle threshold (Ct) value of the reverse transcriptase, a quantitative PCR test will be the primary outcome measure after three days of the treatment. In this study, Ct value of over 38 (negative RT-qPCR) will be taken as a primary outcome measure

Primary outcome would be the percentage of persons having a Ct value over 38 on day 3 (50% in treatment arm and 20% in the control arm – difference of 30%). An effect size (odds ratio) of 4.0 can be detected.

[

Timepoint: at baseline, day 4 and day 7 from the time of ingestion of the first dose.

]

Secondary outcome(s)

1.

The clinical outcome of the patients and improvement of symptoms.

Fever, loss of smell, cough, loss of taste, sore throat, headache, nasal symptoms, shortness of breath, loss of appetite/ nausea/ vomiting, diarrhea, myalgia/ arthralgia

For improvement of symptoms, 50% improvement in treatment arm and 20% in the control arm – difference of 30%: Can detect an effect size (odds ratio) of 4.0.

[

Timepoint: Clinical symptoms-daily from recruitment for a total of seven days.

]
2.

Changes in parameters of full blood count: White cell count more 1×10^9/L (normal white cell count 4.5 to 11.0 × 10^9/L. (Huang & Pranata, 2020). Platelet count 50 × 10^9/L will be considered as an adverse outcome (Wool et al., 2020).

To detect an increase of 1x10^9/L the mean white cell count in the control arm compared to the treatment arm – can detect an effect size of 1.32.

[

Timepoint: At baseline, day 4 and day 7 from the time of ingestion of the first dose.

]
3.

Changes in Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT): 3 times the upper limit of normal (In COVID-19 abnormal ALT/AST is expected depending on severity). Patients with abnormal ALT/AST above 3 times normal will from the baseline will be considered as an adverse outcome.

Assuming that 30% of patients in the treatment arm and 10% of patients in the control arm will have elevated ALT and/or AST more than 3 times the upper limit of normal – can detect an effect size of 3.86.

[

Timepoint: At baseline, day 4 and day 7 from the time of ingestion of the first dose.

]
4.

Renal function impairment: Increase in Serum creatinine (SCr) by > 0.3 mg/dl ( > 26.5 µmol/l) within 48 hours OR increase in SCr to > 1.5 times baseline will be considered as an adverse event (KDIGO criteria, 2012).

Using the same assumptions as above for renal impairment (i.e., increase in serum creatinine >0.3 mg/dl from baseline) to be 30% in the treatment arm and 10% in the control arm, an effect size of 3.86 can be detected.

[

Timepoint: At baseline, day 4 and day 7 from the time of ingestion of the first dose.

]

Target number/sample size

128 (64 in each arm) : to detect a difference of 30% of the proportion of patients showing negative RT-qPCR test from baseline to day four a sample of 64 in each arm total of 128. Primary outcome is the percentage of persons having a Ct value over 38 on d


Countries of recruitment

Sri Lanka


Anticipated start date

2021-01-05


Anticipated end date

2021-01-31


Date of first enrollment


Date of study completion


Recruitment status

Pending


Funding source

Ministry of Health, Sri Lanka


Regulatory approvals

Not applicable



State of Ethics Review Approval


Status

Approved


Date of Approval

2020-12-30


Approval number

ERC/2020/80/4


Details of Ethics Review Committee

Name: ERC of the Faculty of Medicine & Allied Sciences Rajarata University of Sri Lanka
Institutional Address:Faculty of Medicine & Allied Sciences Rajarata University of Sri Lanka Saliyapura, 50008, Sri Lanka
Telephone:0252234462
Email: deanfmas@yahoo.com

Contact & Sponsor Information


Contact person for Scientific Queries/Principal Investigator

Professor Sisira Siribaddana
Professor of Medicine and Consultant Physician
Teaching Hospital, Anuradhapura, Sri Lanka

Mob: 777326940
Fax: 252227706
sisra.siribaddana@gmail.com

Contact Person for Public Queries

Dr Senaka Pilapaitiya
Registered Ayurvedic Practioner, Registered Indigenous Practitioner, Consultant Physician, Dean Faculty of Medicine & Allied Sciences, Rajarata University of Sri Lanka
Jaffna Road, Saliyapura, Sri Lanka

Mob: 777281023
Fax: 252227706
senaka.pilapitiya@gmail.com


Primary study sponsor/organization

Ministry of Production, Supply and Regulation of Pharmaceuticals
Secretary to the Ministry of Production, Supply and Regulation of Pharmaceuticals
385, Suwasiripaya, Rev Baddegama Wimalawansa Thero Mawatha, Colombo-10 Sri Lanka
Tel: 011-2670424
Fax: 011-2670424
psrp.sec@health.gov

Secondary study sponsor (If any)

None





Trial Completion details


Do the investigators plan to share identified individual clinical trial participant-level data (IPD)?

Yes


IPD sharing plan description

The study protocol will be published in an open access journal. All de-identified individual participant data will be available. All data will be available to the Ministry of Health immediately after the study. Data will be available 3 months after publication and up to 5 years after publication for anybody who submits ethical and methodologically sound proposal. Informed consent form, analysis plans and codes can be made available in request. Requests can be directed to the PI or the Ministry of Health, Sri Lanka.


Study protocol available

Yes


Protocol version and date

Version 13 December 30 2020


Protocol URL


Results summary available

No


Date of posting results


Date of study completion


Final sample size


Date of first publication


Link to results


Brief summary of results