Authors: Kiran Ejaz  ( School of Medicine, Emory University Atlanta, GA, USA )
Tanveer Kauser  ( Rollins School of Public Health, Emory University, Atlanta, GA. USA )
Amnah Siddiqa  ( The Jackson Laboratory for Genomics Medicine. )

Here, we present an overview of the clinical trials that are currently being conducted or have concluded to date on COVID-19 globally. A comprehensive search was conducted to present 16 trial registries from around the world. Collectively, there are 1,528 trials reported for COVID-19 to date. Out of them, 50 studies included paediatric age group from day 0 to less than or equal to 18 years of age. A few 18 studies involve only females and 20 only males. There are 2 trials currently underway in Bangladesh, 4 in Pakistan and 13 in India. Overall, 940 trials are related to medicines and/or interventions. They include standard of care for any viral illness, antivirals, anti-inflammatory and immune altering medications. Two out of 10 vaccine trials are novel vaccines. It is knowledgeable and resourceful to reach out to the concerned sponsor if a physician thinks his patient can benefit from the trials in the region.

Keywords: Coronavirus, 2019-nCoV, SARS-CoV-2, 2019nCoV, Clinical Trial, Asia.

DOI: https://doi.org/10.5455/JPMA.37

 

Introduction

 

There are numerous speculations about diagnosis and treatment of the novel coronavirus detected in the end of 2019 (COVID-19) since Wuhan's whistleblowers informed the world about the current outbreak.¹ As members of the scientific community we need to inform our patients and communities with sound scientific information. Hence, we present here an overview of the clinical trials that are currently being conducted or have concluded to date on COVID-19 globally.

 

Methods

 

To have an extensive search, 16 trial registries from around the world were included. These include Australian New Zealand Clinical Trials Registry (ANZCTR),² Chinese Clinical Trial Registry (ChiCTR),³ ClinicalTrials.gov from United States,⁴ Clinical Trials Registry - India (CTRI),⁵ European Union (EU) Clinical Trials Register,⁶ DRKS - German Clinical Trials Register,⁷ Iranian Registry of Clinical Trials,⁸ International Standard Randomized Controlled Trial Number (ISRCTN)⁹ registry by World Health Organization (WHO), International Clinical Trials Registry Platform (ICTRP) and the International Committee of Medical Journal Editors (ICMJE), Japan Primary Registries Network (JPRN),¹⁰ Lebanese Clinical Trials Registry (LBCTR),¹¹ Netherlands Trial Registry (NTR),¹² Pan African Clinical Trial Registry (PACTR),¹³ Brazilian Registry of Clinical Trials (ReBEC),¹⁴ Peruvian Clinical Trials Registry (REPEC),¹⁵ Cuban Public Registry of Clinical Trials (RPCEC),¹⁶ and Thai Clinical Trials Registry (TCTR).¹⁷ All these registries combine their data under the umbrella of WHO to ensure a single point of access and the documentation of trials.¹⁸ We used it to extract all our findings. The data is dynamic and updated frequently. Hence, we report all findings as noted on April 27, 2020.¹⁸ Trials not registered in these registries were excluded. All the trial registries were searched for specific key words, 'COVID-19' and 'SARS-CoV-2' and 'Severe acute respiratory syndrome coronavirus 2' and '2019-nCoV'.

 

Results

Demographics

 

Collectively there are 1,528 trials involving COVID-19 to date.¹⁸ Fifty studies included paediatric age group from day 0 to less than or equal to 18 years of age. Two studies involved newborns up to 1 year of age currently underway in China, of which one is an interventional study testing moxibustion in preventing COVID-19 pneumonia. The other is an observational study about pneumonia due to COVID-19 in neonates.¹⁸

There are 18 studies involving only females.¹⁸ Majority (n=14) are just observational and are related to pregnancy. A researcher from China is studying the impact of the novel virus on ovarian function as a basic science project.¹⁸ A study about diagnostic testing such as detecting the virus in vaginal secretions is also currently underway in China.¹⁸ Two studies are interventional: one related to postpartum depression and another about effects of a mobile meditation application on stress.  There are 20 studies involving only males.¹⁸ Most (n=14) of which are observational while only one is a single validation study about COVID-19 RNA diagnostic kits among males happening in China. Remaining trials included both genders.

There are 2 trials in Bangladesh, 4 in Pakistan and 13 in India. Details of trials currently underway in some Asian countries are mentioned in Table-1.

 

Treatment Trials

 

Scientists are studying treatment options from a vast array of new medications to household remedies noted in various cultures. Overall, 940 trials are related to medicines and/or interventions. The top treatment options currently being studied are considerable.^18,19 They include standard of care for any viral illness, antivirals, anti-inflammatory and immune altering medications. Direct-acting antiviral drugs, LPV/r (lopinivir-ritonavir), LPV/r plus direct-acting antiviral drugs, LPV/r plus interferon, LPV/r plus corticosteroids, favipliravir, remedesivir, umifenovir, umifenovir plus interferon, azithromycin, tocilizumab are the most tested immunosuppressive drugs.^18,19 Others include sarilumab, corticosteroids and hydroxychloroquine plus antivirals. A total of 157 trials include chloroquine phosphate and/or hydroxychloroquine sulphate,¹⁸ used either alone or in combination with another medication. ClinicalTrials.gov reported that a Brazilian study was terminated at early stages due to high death rates associated with the adverse effects linked to higher doses of hydroxychloroquine and azithromycin required to treat the novel virus.²⁰

Seven immunoglobulin and 41 inactivated convalescent plasma and some stem cell therapies are also being tested.¹⁸ Psychological interventions are also being studied for adjacent therapy.

 

Vaccine Trials

 

To date, 10 vaccine trials are underway.¹⁸ Two are novel LV-SMENP-DC and Cuban vaccine CIGB 2020 (CIGB 2020).¹⁸ Others are previously used vaccines that are being tested for their safety and efficacy on COVID19 prevention. These include Bacille Calmette-Guérin (BCG), adenovirus type 5, measles, mumps, and rubella (MMR).

Traditional Chinese Medicine is the most studied other than allopathic medicines. Twenty-eight are traditional, mostly Chinese such as Lianhua Qingwen Capsules.¹⁸ Others are from Iran including medium-chain triglyceride intake and a mixture of Astragalus gossypinus plus food spice based on Ferula assa-foetida mixed in apple juice.

 

Conclusion

 

This is an overview of the clinical trials underway to face this pandemic. It is knowledgeable and resourceful to reach out to the concerned sponsor if a physician thinks that his patient might benefit from the trials in the region.

 

References

 

1.      Sophia Yan, Beijing. International Bar Association [Internet]. London, United Kingdom: Wuhan's whistleblowers; 2012 [updated 2020 April 9; cited 2020Apr 27]. Available from: https://www.ibanet.org/Article/NewDetail.aspx?ArticleUid=D0E01D66-E92A-419A-B0E0-2A1732341FAD

2.      Australian New Zealand Clinical Trials Registry [Internet] Sydney (NSW): NHMRC Clinical Trials Centre, University of Sydney (Australia); 2005. About us; 2012 [cited 2020 Apr 27]. Available from: https://www.anzctr.org.au/TrialSearch.aspx

3.      Chinese Clinical Trial Register [Internet] Chengdu (Sichuan): Ministry of Health (China). 2007 Jun 27 [cited 2020 Apr 27]. Available from: http://www.chictr.org.cn/abouten.aspx

4.      ClinicalTrials.gov [Internet] Bethesda, MD: National Library of Medicine (US). 2000 Feb 29 - . [cited 2020 Apr 27]. Available from: https://clinicaltrials.gov/ct2/about-site/background

5.      Clinical Trials Registry India [Internet] New Delhi: Database Publisher (India). 2007 Jun 20 - . [cited 2020 Apr 27]. Available from: http://ctri.nic.in/Clinicaltrials/login.php

6.      European Union (EU) Clinical Trials Register. European Medicines Agency [Internet]. Amsterdam, The Netherlands; 1995 [cited 2020 Apr 27]. Available from: https://www.clinicaltrialsregister.eu/

7.      German Clinical Trials Register. [Internet] Cologne, Germany [updated 2019 Jan 09; cited 2020 Apr 27]. Available from: https://www.drks.de/drks_web/

8.      Iranian Registry of Clinical Trials [Internet] Tehran, Iran; 2008 [updated 2012 Jun 15; cited 2020 Apr 27]. Available from: https://www.irct.ir/

9.      Current Controlled Trials [Internet] London: BioMed Central [ cited 2020 Apr 27]. Available from: https://www.isrctn.com/page/about

10.    Japan Primary Registries Network [Internet] Japan [cited 2020 Apr 27]. Available from: http://rctportal.niph.go.jp/link.html

11.    Lebanese Clinical Trials Registry. Ministry of Public Health [Internet] Ogero Beirut - Lebanon: Diabetes Australia; 2020 [updated 2012 Jun 15; cited 2020 Apr 27]. Available from: http://lbctr.emro.who.int/

12.    Nederlands Trial Register [Internet] Amsterdam: Academic Medical Center The Netherlands. 2004 Oct 26 [cited 2020 Apr 27]. Available from: http://www.trialregister.nl

13.    Pan African Clinical Trial Registry [Internet] Tygerberg, South Africa; 2020 [cited 2020 Apr 27]. Available from: https://pactr.samrc.ac.za/

14.    Brazilian Registry of Clinical Trials Oswaldo Cruz Foundation [Internet] Rio de Janeiro, RJ Brazil [cited 2020 Apr 27]. Available from: http://www.ensaiosclinicos.gov.br/

15.    Peruvian Clinical Trials Registry. National Institute of Health [Internet] Lima, Perú [cited 2020 Apr 27]. Available from: https://ensayosclinicos-repec.ins.gob.pe/en/

16.    Cuban Public Registry of Clinical Trials. [Internet] La Habana, Cuba: 2014 [cited 2020 Apr 27]. Available from: http://registroclinico.sld.cu/en/home

17.    Thai Clinical Trials Registry. Medical Research Foundation [Internet] Bangkok, Thailand [cited 2020 Apr 27]. Available from: https://www.clinicaltrials.in.th/

18.    International Clinical Trials Registry Platform. World Health Organization. [Internet] Geneva [updated 2020; cited 2020 Apr 27]. Available from: https://www.who.int/ictrp/en/

19.    Thorlund K, Dron L, Park J, Hsu G, Forrest JI, Mills EJ. A real-time dashboard of clinical trials for COVID-19. Lancet Digital Health 2020. doi: 10.1016/S2589-7500(20)30086-8.

20.    Azidus Brasil. Efficacy and safety of hydroxychloroquine and azithromycin for the treatment of hospitalized patients with moderate to severe COVID-19. ClinicalTrials.gov [Internet] Bethesda, MD: National Library of Medicine (US) [updated 2020 Apr 22; cited 2020 Apr 27]; [about 6 screens]. Available from: https://clinicaltrials.gov/ct2/show/NCT04329572?recrs=g&cond=COVID-19&draw=2&rank=1.