Slctr

Randomized Double-Blind Phase II Clinical Trial to Assess the Efficacy and Safety of an Ayurvedic Formulation, in COVID-19 Infected Patients

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SLCTR Registration Number

SLCTR/2021/002

Date of Registration

08 Jan 2021

The date of last modification

Aug 26, 2022

Trial Status

Application Summary

Scientific Title of Trial

Randomized Double-Blind Phase II Clinical Trial to Assess the Efficacy and Safety of an Ayurvedic Formulation, in COVID-19 Infected Patients

Public Title of Trial

Efficacy and safety of Link Natural Sudarshana tablet (an Ayurvedic medicine) against COVID-19 infection – A single center, randomized double-blind, placebo-controlled clinical trial

Disease or Health Condition(s) Studied

COVID-19

Scientific Acronym

None

Public Acronym

None

Brief title

Link Natural Sudarshana tablet, an Ayurvedic formulation against COVID-19

Universal Trial Number

U1111-1263-2664

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

EC-20-EM08, UOC

Trial Details

What is the research question being addressed?

Is Link Natural Sudarshana Tablet, an Ayurvedic formulation, efficacious and safe against COVID-19 infection?

Type of study

Interventional

Study design

Allocation

Randomized controlled trial

Masking

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

Control

Placebo

Assignment

Parallel

Purpose

Treatment

Study Phase

Phase 2

Intervention(s) planned

This study will be conducted at the National Institute of Infectious Diseases, Angoda, Sri Lanka. Patients who fulfill the inclusion criteria will be randomized into two groups using computer-generated random numbers. One group will receive the investigational medicinal product, Link Natural Sudarshana Tablet [Ingredients found in Bhaisajya Ratnavali, Sharangadhara Samhitha, Ayurveda Pharmacopoeia of Sri Lanka and Ayurveda Formulary of India] which will be given as two tablets 8 hrly for 10 days, and the other group will receive a placebo containing microcrystalline cellulose BP., maize starch BP., sodium starch glycolate BP., carboxymethyl cellulose BP., aerosil 200 Pharma., magnesium stearate BP [All excipients in the investigational medicine other than the active ingredient] also two tablets, 8 hrly for 10 days. Both groups will receive standard treatment according to the Ref. Circular no. Epid/400/2019n-cov, Ministry of Health, Sri Lanka. According to the present guideline, patients will be discharged after 14 days or more (Ref. Circular no. DDG/LS/CV-GL/2020, Ministry of Health,, Sri Lanka).

Inclusion criteria

• Patients who are over 18 years of age

• Both male and female

• Confirmed diagnosis of COVID-19 by a PCR test nasopharyngeal/throat/sputum swab within 48 hours prior to randomization [at hospital reception before admission]

• Onset of one or more of COVID-19 related symptoms and/or signs of mild to moderate disease within 96 hours prior to randomization. [Symptoms of mild disease are: i. Fever ii. Cough iii. Sore throat iv. Malaise v. Headache vi. Muscle pain vii. Gastrointestinal symptoms. Signs of moderate disease (in addition to symptoms of mild disease) i. Shortness of breath with exertion ii.Respiratory rate >= 20 but <30/min iii.Saturation of oxygen >93% of room air iv.Heart rate >= 90/min but <125/min]

Exclusion criteria

Patients who have a known allergy to the Ayurveda drug Sudarshana Cúrna or Link Natural Sudarshana Tablet (LNST) or any of its components.
Pregnant women (confirmed or suspected with a history of a missing menstrual period for more than a week)
Breast-feeding mothers
Patients with cerebrovascular disease, or stroke, or ischaemic heart disease, or diabetes, or hypertension, or history of liver disease, or renal disease (all the patients will be screened for diabetes (DM), or high blood pressure (BP). Even without a history DM or high BP, if the random blood sugar done on admission is >200 mg/dL, or if the systolic blood pressure is >140 or diastolic blood pressure is > 90 mmHg, they will be excluded from the study)
Patients with severe disease as indicated by SpO2 <=93% on room air at sea level or PaO2/FiO2 < 300, respiratory rate >=30 per minute, heart rate >=125 per minute (38c)

*Patients with critical disease ie. those who require mechanical ventilation or anticipated impending need for mechanical ventilation

Primary outcome(s)

1. 87% reduction of viral burden by measuring semi-quantitative viral RNA of SARS-COV-2 as measured by cycle threshold from nasopharyngeal swabs. (viral burden is calculated using the Ct values as done in BALZE-1 study protocol. Ref. Chen, P.et al. (2020). SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19. New England Journal of Medicine.doi:10.1056 /nejmoa2029849)	[ Day 11 from the date of intervention ]
2. Clinical progression using the WHO ordinal outcome scale - WHO Working Group on the Clinical Characterisations and Management of COVID-19 infection. A minimal common outcome measure set for COVID-19 clinical research. Lancet Infect Dis 2020. Published Online June 12, 2020. https://doi.org /10.1016/S1473-3099(20)30483-7)	[ Day 6, 10 and 14 from the date of intervention ]

Secondary outcome(s)

1. Reduction of symptom score by 50% by day 6 and by 100% by day 10 of intervention ( Each symptom is scored daily by the participant as absent (score 0), mild (1), moderate (2) or severe (3) as used in the BLAZE-1 study)	[ Day 6, 10 and 14 of hospital stay ]
2. 100% reduction of hospital stay to 14 days	[ At discharge from the hospital. ]
3. 50% reduction of development of hypoxia (SPO2 <94%. Reference: Wang Y. et al. Remdesivir in adults with severe COVID-19: A randomised,double-blind, placebo-controlled, multicentre trial. Lancet 2020; 395: 1569–78 https://doi.org/10.1016/S0140-6736(20)31022-9)	[ Throughout the hospital stay ]
4. 100% normalization of C-Reactive protein (CRP), Erythrocyte Sedimentation Rate (ESR), Aspartate aminotransferease (AST), Alanine aminotransferase (ALT), and serum creatinine by day 14 of intervention.	[ Every 4th day of hospital stay since enrollment ]
5. 50% improvement of lymphopaenia by day 10 and 100% improvement by day 14. (lymphopaenia= lymphocyte count <1•0 × 109/L. Reference: Huang C. et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 15-21 February; 395(10223): 497–506. doi: 10.1016/S0140-6736(20)30183-5)	[ Every 4th day of hospital stay since enrollment ]
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Target number/sample size

154 (77 in a group)

Countries of recruitment

Sri Lanka

Anticipated start date

2021-01-08

Anticipated end date

2021-03-31

Date of first enrollment

2021-01-08

Date of study completion

Recruitment status

Complete: follow up complete

Funding source

Link Natural Products (Pvt) Ltd,199, Kew Road, Colombo 02

Regulatory approvals

Not applicable.

State of Ethics Review Approval

Status

Approved

Date of Approval

2020-12-17

Approval number

EC-20-EM 08

Details of Ethics Review Committee

Name:	Ethics Review Committee of the Faculty of Medicine
Institutional Address:	Faculty of Medicine. University of Colombo. No.25,Kynsey Road, Colombo 08. Sri Lanka.
Telephone:	+94 112 695 300 ext: 240
Email:	ethicscommitteemfc@gmail.com

Contact & Sponsor Information

Contact person for Scientific Queries/Principal Investigator

Dr. Ananda Wijewickrama
Consultant Physician
National Institute of Infectious Disease Mandawila road, Angoda, Sri Lanka.
+94112411224
0777559398
+94112410031
anandawijewickrama012@gmail.com

Contact Person for Public Queries

Ananda Wijewickrama
Consultant Physician
National Institute of Infectious Disease Mandawila road, Angoda, Sri Lanka.
+941122411224
0777559398
+94112410031
anandawijewickrama012@gmail.com

Primary study sponsor/organization

Link Natural Products (Pvt) Ltd

199, Kew Road, Colombo 02, Sri Lanka.
+94 115 60 60 60
+94 112 409 293
info2@linknaturalproducts.com
https://linknaturalproducts.com/

Secondary study sponsor (If any)

Trial Completion details

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

Yes

IPD sharing plan description

Individual participant data that underlie the results reported in the publication of results, after de-identification (text, tables, figures, and appendices), will be shared. The study protocol and Statistical Analysis Plan will be shared. Data will be available beginning 3 months and ending 5 years following article publication. Data will be shared with investigators whose proposed use of the data has been approved by an independent review committee (“learned intermediary”) identified for this purpose. Data will be available for individual participant data meta-analysis. Data will be available for proposals submitted up to 36 months following publication of results.

Study protocol available

Yes

Protocol version and date

Version 2.2 received by ERC on 2020.12.07

Protocol URL

Results summary available

Date of posting results

Date of study completion

Final sample size

Date of first publication

Link to results

Brief summary of results