CTRI Number	CTRI/2020/05/025214 [Registered on: 15/05/2020] Trial Registered Prospectively
Last Modified On:	13/04/2021
Post Graduate Thesis	No
Type of Trial	Interventional
Type of Study	Drug Ayurveda
Study Design	Randomized, Parallel Group, Active Controlled Trial
Public Title of Study	To observe the effect of Ayurvedic medicine for the treatment of COVID-19
Scientific Title of Study	A Randomized, Open Label, Parallel Efficacy, Active Control, Exploratory Clinical Trial to Evaluate Efficacy and Safety of an Ayurvedic Formulation (AYUSH 64) as Adjunct Treatment to Standard of Care for the management of Mild to Moderate COVID-19 Patients
Secondary IDs if Any	Secondary ID  Registry  NIL  NIL
Details of Principal Investigator or overall Trial Coordinator (multi-center study) Modification(s)	Name  Dr Sumit Shrivastva  Address  77, Chandi Path, Sector 46B, Sector 46 Ward No. 1 to 5 (General ward Male and Female) Chandigarh CHANDIGARH 160047 India  Phone  9781110780   Fax     Email  sumitpankaj@gmail.com
Details Contact Person Scientific Query Modification(s)	Name  Dr Sumit Shrivastva  Address  77, Chandi Path, Sector 46B, Sector 46 Room No. 116, Ground floor, Shri Dhanwantry Ayurvedic Hospital Chandigarh CHANDIGARH 160047 India  Phone  9781110780   Fax     Email  sumitpankaj@gmail.com
Details Contact Person Public Query Modification(s)	Name  Dr Sumit Shrivastva  Address  77, Chandi Path, Sector 46B, Sector 46 Room No. 116, Ground floor, Shri Dhanwantry Ayurvedic Hospital Chandigarh CHANDIGARH 160047 India  Phone  9781110780   Fax     Email  sumitpankaj@gmail.com
Source of Monetary or Material Support	Central Council for Research in Ayurvedic Sciences, New Delhi
Primary Sponsor	Name  Central Council for Research in Ayurvedic Sciences  Address  Jawahar Lal Nehru Bhartiya Chikitsa Evam Homoeopathy Anusandhan Bhawan 61-65, Institutional Area, Opposite D-Block, Janakpuri, New Delhi-110058   Type of Sponsor  Government funding agency
Details of Secondary Sponsor	Name  Address  NIL  NIL
Countries of Recruitment	India
Sites of Study Modification(s)	No of Sites = 1   Contact Person  Name of Site  Site Address  Phone/Fax/Email  Dr Sumit Shrivastva  Shri Dhanwantry Ayurvedic College and Hospital  Room No. 116, Ground floor, Shri Dhanwantry Ayurvedic Hospital 77, Chandi Path, Sector 46 B, Sector 46 Chandigarh   9781110780 sumitpankaj@gmail.com
Details of Ethics Committee	No of Ethics Committees= 1   Name of Committee  Approval Status  Institute Ethics Committee Central Ayurveda Research Institute for Respiratory Disorders Moti Bagh Road Patiala Punjab 147001  Approved
Regulatory Clearance Status from DCGI	Status  Not Applicable
Health Condition / Problems Studied Modification(s)	Health Type  Condition  Patients  Coronavirus as the cause of diseases classified elsewhere
Intervention / Comparator Agent	Type  Name  Details  Intervention  AYUSH 64  Dose:2 capsules (500 mg each) thrice daily Dosage form:Capsules/Tablets Route of Administration: Oral Time of Administration: Thrice a day after food Anupana: Water Duration of therapy: 30 days   Comparator Agent  Conventional standard therapy for COVID-19 positive patients   Conventional standard therapy as per ICMR/WHO parameters
Inclusion Criteria	Age From  18.00 Year(s) Age To  75.00 Year(s) Gender  Both  Details  1.Typical clinical presentation of acute onset febrile illness with cough and a RT_PCR based laboratory confirmation test for COVID-19 2.Typical clinical presentation of acute onset febrile illness with sore throat and dry cough with or without shortness of breath in a patient from a known ‘hot spot’ area or in close contact with a confirmed COVID-19 case with a negative laboratory test for COVID 19 and H1N1 influenza 3.Patients with either sex, 18 to 75 years age 4.Patients with mild-moderately severe disease 5.All patients must agree not to share medication 6.Patients willing to participate and sign an informed consent Understands and agrees to comply with planned study procedures. 7.Agrees to the give OP swabs and venous blood for testing as per protocol.
ExclusionCriteria	Details  1. Patients suffering from severe COVID-19 Disease as judged by a physician and fulfilling at least two of the following three criteria (i) Respiratory distress at room ambience (equal or more than 30 breaths per min) (ii) Oxygen saturation at rest equal or less than 93% (peripheral digital arterial oxymetry) and requiring oxygen support for over one hour to normalize (iii) Any of the known COVID-19 complications and emergency procedures which may require shift/admission in intensive care unit such as respiratory failure, adult respiratory distress syndrome, requirement of oxygen support for over 1 hour, requirement of mechanical ventilation, septic shock, or severe non-respiratory organ dysfunction or failure. 2.Chronic, Severe, Unstable, Uncontrolled co-existent medical illness such as Diabetes, Hypertension, Cardiac disorders, liver, kidney disorders and lung disorders or other disease of concern which may put the patient at increased risk during the study 3. History of immunosuppression: solid organ or bone marrow transplant, use of immunosuppressive antimetabolic and biologic agents, intrinsic immunodeficiencies, HIV infection. 4. Active cancer diagnosis, on palliative treatment or requiring current therapy with antimetabolic agents, immunotherapy or radiotherapy. 5. Patients on parenteral nutrition 6. Patients with known sensitivity or contraindication to any of the ingredients of study medication 7. History of bleeding haemorrhoids, haemoptysis, acid peptic diseases, ulcers and pulmonary diseases (tuberculosis, asthma, etc.) 8. Patients who are likely to worsen or planed ICU admission or ventilator support due to any reason 9. Pregnancy and lactation 10. Participation in a drug interventional clinical drug trial of any nature in the three month period preceding onset of COVID-19 11. Participation in any other clinical trial of an experimental agent treatment for COVID-19 12. Patients on any kind of Ayurveda treatment or any other alternative and complementary medicinal systems such as Homeopathy, Unani, Siddha and in particular requiring oral therapy of any kind. 13. Physician decision that involvement in the study is not in the patient´s best interest
Method of Generating Random Sequence	Computer generated randomization
Method of Concealment	An Open list of random numbers
Blinding/Masking	Open Label
Primary Outcome	Outcome  TimePoints  a) Mean time (days) for clinical recovery [Day of randomization to the day of clinical recovery b) Proportion of patients showing ‘clinical recovery’.   On 7th day, 15th day, 23rd day and 30th day
Secondary Outcome	Outcome  TimePoints  Improvement in the symptoms,supported by in lab investigations and other radiological examination  On baseline and 30th day
Target Sample Size	Total Sample Size="80" Sample Size from India="80"
Phase of Trial	Phase 2/ Phase 3
Date of First Enrollment (India)	24/05/2020
Date of First Enrollment (Global)	No Date Specified
Estimated Duration of Trial	Years="0" Months="6" Days="0"
Recruitment Status of Trial (Global) Modification(s)	Not Applicable
Recruitment Status of Trial (India)	Completed
Publication Details Modification(s)	under publication
Brief Summary	COVID-19 has emerged as the latest pandemic, that erupted in the Wuhan City of People’s Republic of China in December 2019, which is affecting human health and economy across the world. 1133758 cases have been reported globally as on April 5, according to the WHO Coronavirus disease 2019 (COVID-19) Situation Report – 76. The occurrence of the ongoing COVID-19 in developed countries also highlights the fact that developed countries and rich populations are not immune to the outbreaks of infectious diseases. Coronaviruses (CoVs) belong to the family Coronaviridae and are enveloped, single-stranded, positive-sense RNA viruses. The SARS-CoV-2 belongs to the beta CoV genus which also includes the SARS-CoV-1 and the MERS-CoV. The lack of approved effective drug therapeutic protocols for CoVs would be a challenge for the treatment of the newly emerged COVID-19 infections worldwide. Drug repurposing, which is defined as identifying alternative uses for approved or investigational drugs outside their defined indication, could be a possible way to overcome the time limitation of research and development needed to design a therapeutic drug to combat the pathogen. The drug repurposing or repositioning approach thus can facilitate prompt clinical decisions at lower costs than de novo drug development. Though drug repurposing is sometimes based on chance observations, target-based repurposing of drugs depends on prior understanding of the precise molecular or cellular element that is recognized by the proposed drug. Ayurveda and traditional systems of Medicine in India have been treating diseases of infectious and non-infectious origin equally with expansive success rates, treating the patients through an individualized person to person approach depending upon the presentation of clinical symptoms in each. Central Council for Research in Ayurvedic Sciences, apex body for research and development in Ayurveda in India under Ministry of AYUSH has developed a poly-herbal drug ‘AYUSH 64’ through extensive pharmacological, toxicological and clinical studies. The experimental studies of AYUSH 64 has shown that it was safe and non-toxic in the dose of 500 mg/kg of body weight for 12 weeks. It is found to be effective in fevers of unknown etiology, filarial lymphangitis and derangement of liver function besides its anti-malarial activity. Taking leads from the clinical experiences of physicians who had successfully used AYUSH-64, for management of Influenza like Illness (ILI), a pilot study was conducted by this Council, which was concluded recently and is under the process of publication. This study was done in 30 cases of flu like illness, among whom, 28 participants recovered without any further medication. This lead to the idea of repurposing AYUSH 64 for use in the management of Covid-19 positive cases which also present with Influenza like symptoms owing to affliction of respiratory tract. The composition of AYUSH 64 includes, Saptaparna (Alstonia scholaris R. Br.) Katuki (Picrorhiza kurroa Royle ex. Benth), Kiratatikta (Swertia Chirata Pexbex. Karst) and Kuberaksha (Caesalpinia crista Linn.). Studies on the ingredients of AYUSH-64 has shown anti-inflammatory and immunomodulatory activities. Animal study has demonstrated that total alkaloids from Saptaparna inhibited the production of inflammatory cytokines TNF-α and IL-8 in the BALF and lung. Swertia chirata showed antiviral properties against Herpes simplex virus type-1 and crude extract of the whole Swertia chirata plant inhibited the expression of Vpr in Hela cells harboring the TREx plasmid encoding full-length Vpr (TREx-HeLa-Vpr cells).