Ongoing Clinical Trials for the Management of the COVID-19 Pandemic
Authors: Mark P. Lythgoe, Paul Middleton
Journal: Trends in Pharmacological Sciences (2020)

COVID-19 has rapidly developed into a worldwide pandemic with a significant health and economic burden. There are currently no approved treatments or preventative therapeutic strategies. Hundreds of clinical studies have been registered with the intention of discovering effective treatments. Here, we review currently registered interventional clinical trials for the treatment and prevention of COVID-19 to provide an overall summary and insight into the global response. COVID-19 has rapidly developed into a worldwide pandemic with a significant health and economic burden. There are currently no approved treatments or preventative therapeutic strategies. Hundreds of clinical studies have been registered with the intention of discovering effective treatments. Here, we review currently registered interventional clinical trials for the treatment and prevention of COVID-19 to provide an overall summary and insight into the global response. Over the past two decades, three novel pathogenic human coronaviruses have emerged from animal reservoirs [1.Paules C.I. et al.Coronavirus infections: more than just the common cold.JAMA. 2020; 323: 707-708Crossref Scopus (1385) Google Scholar]. These are Middle East respiratory syndrome-related coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), and, most recently, severe acute respiratory syndrome coronavirus 2 (referred to as COVID-19, SARS-CoV-2, or 2019-nCoV). All three have led to global health emergencies, with significant morbidity and mortality [2.Song Z. et al.From SARS to MERS, thrusting coronaviruses into the spotlight.Viruses. 2019; 11: 59Crossref PubMed Scopus (811) Google Scholar]. Before 2020, the largest outbreak was of SARS-CoV in 2003, which affected over 8000 individuals globally and was associated with 774 deaths (case fatality rate of 9.6%)i [3.de Wit E. et al.SARS and MERS: recent insights into emerging coronaviruses.Nat. Rev. Microbiol. 2016; 14: 523-534Crossref PubMed Scopus (2429) Google Scholar]. The overall cost to the global economy of SARS-CoV was estimated to be between US$30 billion and US$100 billion [4.Keogh-Brown M.R. Smith R.D. The economic impact of SARS: how does the reality match the predictions?.Health Policy. 2008; 88: 110-120Crossref PubMed Scopus (226) Google Scholar]. Following the first identification in patients with severe pneumonia in Wuhan province, China in November 2019, COVID-19 has spread rapidly and now affects all permanently inhabited continents. This is the greatest pandemic of modern times and has been declared a Public Health Emergency of International Concern by the WHO Director-Generalii. As of 27 March 2020 (date of submission), COVID-19 was affecting 199 countries and territories, with >510 000 confirmed cases globallyiii. It is associated with an estimated mortality of between 1% and 5%iii. Furthermore, human-to-human transmission has continued apace, despite escalating public health measures. Current estimates of the impact on the worldwide economy are US$1 trillion and risingiv. Currently, there are no approved therapies for either the treatment or prevention of COVID-19. With the predicted number of cases set to rise significantly, this represents a prodigious acute unmet medical need. Several national and international research groups are working collaboratively on a variety of preventative and therapeutic interventions. Potential avenues being explored include vaccine development, convalescent plasma, interferon-based therapies, small-molecule drugs, cell-based therapies, and monoclonal antibodies (mAbs) [5.Li G. de Clercq E. Therapeutic options for the 2019 novel coronavirus (2019-nCoV).Nat. Rev. Drug Discov. 2020; 19: 149-150Crossref PubMed Scopus (1248) Google Scholar]. However, drug therapy development is a costly and timely process with a high attrition rate [6.Lythgoe M.P. et al.Why drugs fail in clinical trials in pulmonary arterial hypertension, and strategies to succeed in the future.Pharmacol. Ther. 2016; 164: 195-203Crossref PubMed Scopus (39) Google Scholar]. The speed of the normal drug development pathway is unacceptable in the context of the current global emergency. Therefore, there has been considerable interest in repurposing existing drugs and expediting developmental antiviral treatments, such as those for influenza, hepatitis B (HBV), hepatitis C (HCV), and filoviruses, to allow more rapid development [5.Li G. de Clercq E. Therapeutic options for the 2019 novel coronavirus (2019-nCoV).Nat. Rev. Drug Discov. 2020; 19: 149-150Crossref PubMed Scopus (1248) Google Scholar]. The swift genomic sequencing of COVID-19 has facilitated this process, allowing comparison with MERS-CoV, SARS-CoV, and other morbific viruses [7.Lu R. et al.Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding.Lancet. 2020; 395: 565-574Abstract Full Text Full Text PDF PubMed Scopus (8314) Google Scholar]. This strategy has identified several genomic regions of interest for therapeutic modulation, specifically the identification of highly conserved regions involving viral enzymes between different pathogenic coronaviruses. Since 2005, it has been recommended by the International Committee of Medical Journal Editors (ICMJE) that all clinical trials should be registered in publicly available domains before they may be considered for publication [8.De Angelis C. et al.Clinical trial registration: a statement from the International Committee of Medical Journal Editors.Lancet. 2004; 364: 911-912Abstract Full Text Full Text PDF PubMed Scopus (256) Google Scholar]. The introduction of this requirement and other initiatives to increase clinical trial transparency has contributed to an increasing number of trials being recorded in online registries, such as ClinicalTrials.govv and the International Clinical Trials Registry Platform (ICTRP)vi of the WHO. The logging of trials on registries has vastly facilitated the dissemination of information across several domains, including intervention, methodology, patient group, and outcome measures. Furthermore, in the event of the nonpublication of results, it means that trial information remains freely available for analysis. In the context of the current global COVID-19 pandemic, we performed an analysis of online registries (ClinicalTrials.govv, WHO ICTRPvi, EU Clinical Trials Registervii, and Cochrane Central Register of Controlled Trialsviii; Figure 1) to collate all registered therapeutic and preventative interventions under clinical investigation. We hope that this will clarify current investigational advances and guide potential future strategies. We identified 344 interventional studies focusing on both preventative strategies and the treatment of patients with COVID-19 (Figure 1) as of 20 March 2020. This search identified 100 studies that focused on forms of traditional Chinese medicine (TCM), including herbal medicines, acupuncture and other forms of complementary medicine. These have not been further analysed due to a lack of scientific rationale, inadequate provision of information regarding active ingredients, and limited applicability to mainstream medical practice. Table 1 (Key Table) shows interventional treatments (Table 1A) and preventative strategies (Table 1B) under clinical investigation for COVID-19.Table 1Key Table. Ongoing Clinical Trials for the (A) Treatment and (B) Prevention of COVID-19 (Current as of 20 March, 2020)aAbbreviations: Ad5, adenovirus type 5; APC, antigen-presenting cells; CIK cells, cytokine-induced killer cells; CRRT, continuous renal replacement therapy; DC, dendritic cell; ECMO, extracorporeal membrane oxygenation; IVIG, intravenous immunoglobulin; MSCs, mesenchymal stem cells; NK cells, natural killer cells; rhG-CSF, recombinant human granulocyte colony-stimulating factor; rSFIN-co, recombinant supercompound interferon; TFF2, Trefoil factor 2; vMIP, viral macrophage inflammatory protein.Clinical trial ID (Registry)InterventionbFor part (B), this column indicates the intervention to prevent infection.SizecParticipant size as stated in registry entry.RandomisedBlindedStatusCountry of origin (pharma sponsor)(A) Ongoing clinical trials for treatment of COVID-19AntiviralChiCTR2000029609 (ICTPR)Arm A (mild–moderate): chloroquineArm B (mild–moderate): lopinavir/ritonavirArm C (mild–moderate): lopinavir/ritonavir + chloroquineArm D (severe): lopinavir/ritonavirArm E (severe): chloroquine205NoNoRecruitingChinaChiCTR2000029600 (ICTPR)Arm A: interferon alpha atomisationArm B lopinavir/ritonavir and interferon alpha atomisationArm C: favipiravir and interferon alpha atomisation90NoNoRecruitingChinaNCT04261270 (ClinicalTrials.gov)Arm A: ASC09 and oseltamivirArm B: ritonavir and oseltamivirArm C: oseltamivir60YesSingleRecruitingChinaNCT04261907 (ClinicalTrials.gov)Arm A: ASC09/ritonavirArm B: lopinavir/ritonavir160YesNoRecruitingChina (Ascletis Pharm)ChiCTR2000030487 (ICTPR)Arm A: azvudine10NoNoRecruitingChinaChiCTR2000030424 (ICTPR)Arm A: azvudine30NoNoNot recruitingChinaChiCTR2000030041 (ICTPR)Arm A: azvudine40NoNoNot recruitingChinaChiCTR2000029853 (ICTPR)Arm A: azvudineArm B: standard treatment20YesNoRecruitingChinaChiCTR2000029544 (ICTPR)Arm A: baloxavir marboxilArm B: favipiravirArm C: standard treatment30YesUnspecifiedNot recruitingChinaChiCTR2000029548 (ICTPR)Arm A: baloxavir marboxilArm B: favipiravirArm C: lopinavir/ritonavir30YesNoNot recruitingChinaChiCTR2000030001 (ICTPR)Arm A: basic treatment + triazavirinArm B: basic treatment240YesYesRecruitingChinaNCT04273763 (ClinicalTrials.gov)Arm A: bromhexine (mucolytic), umifenovir, interferon a2b, and favipiravirArm B: umifenovir and interferon a2b60YesNoRecruitingChina (WanBangDe Pharm. Group)ChiCTR2000030002 (ICTPR)Arm A: conventional treatmentArm B: conventional treatment + tranilast60YesNoRecruitingChinaChiCTR2000030472 (ICTPR)Arm A: danoprevir/ritonavirArm B: standard treatment20UnspecifiedNoRecruitingChinaChiCTR2000030259 (ICTPR)Arm A: danoprevir/ritonavirArm B: standard treatment60YesUnspecifiedRecruitingChinaChiCTR2000030000 (ICTPR)Arm A: danoprevir/ritonavirArm B: PegasysArm C: NovaferonArm D: CoriolusArm E: standard treatment50UnspecifiedNoRecruitingChinaNCT04252274 (ClinicalTrials.gov)Arm A: darunavir and cobicistatArm B: standard treatment30YesNoRecruitingChinaNCT04304053 (ClinicalTrials.gov)Arm A: darunavir/cobicistatArm B: isolation3040YesNoRecruitingSpainChiCTR2000029541 (ICTPR)Arm A: darunavir/cobicistat and thymosinArm B: lopinavir/ritonavir and thymosinArm C: thymosin100YesNoNot recruitingChinaNCT04291729 (ClinicalTrials.gov)Arm A: darunavir/ritonavir and atomised interferonArm B: peginterferon a2Arm C: interferon alpha (Novaferon)Arm D: lopinavir/ritonavirArm E: atomised interferon + Chinese medicine (unspecified)50NoNoRecruitingChina (Ascletis Pharmaceutical)ChiCTR2000030535 (ICTPR)Arm A: ebastine and interferon alpha inhalation and lopinavirArm B: interferon alpha inhalation and lopinavir100YesSingleRecruitingChinaChiCTR2000030113 (ICTPR)Arm A: favipiravirArm B: ritonavir20YesNoRecruitingChinaChiCTR2000030254 (ICTPR)Arm A: favipiravirArm B: umifenovir240YesNoRecruitingChinaChiCTR2000030987 (ICTPR)Arm A: favipiravir and chloroquineArm B: favipiravirArm C: placebo150YesUnspecifiedRecruitingChinaNCT04310228 (ClinicalTrials.gov)Arm A: favipiravir and tocilizumabArm B: favipiravirArm C: tocilizumab150YesNoRecruitingChinaChiCTR2000029895 (ICTPR)Arm A: GD31160NoUnspecifiedRecruitingChinaIRCT20100228003449N27 (ICTPR)Arm A: hydroxychloroquine, lopinavir/ritonavir, and interferon beta 1bArm B: hydroxychloroquine and lopinavir/ritonavir30YesNoRecruitingIranIRCT20100228003449N28 (ICTPR)Arm A: hydroxychloroquine, lopinavir/ritonavir, and interferon beta 1aArm B: hydroxychloroquine and lopinavir/ritonavir30YesNoRecruitingIranIRCT20100228003449N29 (ICTPR)Arm A: hydroxychloroquine, lopinavir/ritonavir, and sofosbuvir/ledipasvirArm B: hydroxychloroquine and lopinavir/ritonavir50YesNoRecruitingIranJPRN-jRCTs041190120 (ICTPR)Arm A: immediate favipiravir (Day 1–10)Arm B: delayed favipiravir (Day 6–15)86YesNoRecruitingJapan2020-001023-14 (EU-CTR)Arm A: inhaled interferon alpha 1bArm B: placebo400YesDoubleRecruitingUK (Synairgen Ltd)ChiCTR2000029989 (ICTPR)Arm A: interferon a1b eye dropsArm B: placebo eye drops300YesUnspecifiedNot recruitingChinaNCT04293887 (ClinicalTrials.gov)Arm A: interferon a1b nebulisedArm B: standard treatment328YesNoNot recruitingChinaChiCTR2000030922 (ICTPR)Arm A: interferon alpha 2a and ribavirinArm B: umifenovir and ribavirin30YesUnspecifiedRecruitingChinaChiCTR2000029308 (ICTPR) [11.Cao B. et al.A trial of lopinavir–ritonavir in adults hospitalized with severe Covid-19.N. Engl. J. Med. 2020; (Published online March 18. 2020. https://doi.org/10.1056/NEJMoa2001282)Crossref Scopus (3870) Google Scholar]Arm A: lopinavir/ritonavirArm B standard treatment160YesNoRecruitingChinaNCT04307693 (ClinicalTrials.gov)Arm A: lopinavir/ritonavirArm B: hydroxychloroquineArm C: no intervention150YesNoRecruitingSouth KoreaChiCTR2000030187 (ICTPR)Arm A: lopinavir/ritonavirArm B: standard of care60YesUnspecifiedRecruitingChina2020-001113-21 (EU-CTR)Arm A: lopinavir/ritonavirArm B: dexamethasoneArm C: interferon beta 1aArm D: placebo2000YesNoRecruitingUK2020-000936-23 (EU-CTR)Arm A: lopinavir/ritonavirArm B: interferon beta 1aArm C: remdesivir3000YesNoRecruitingFranceNCT04251871 (ClinicalTrials.gov)Arm A: lopinavir/ritonavir and interferon alpha inhalation and traditional Chinese medicineArm B: lopinavir/ritonavir and interferon alpha inhalation150YesNoRecruitingChinaChiCTR2000029468 (ICTPR)Arm A: lopinavir/ritonavir and emtricitabine/tenofovirArm B: lopinavir/ritonavir120UnspecifiedUnspecifiedNot recruitingChinaJPRN-jRCTs031190227 (ICTPR)Arm A: lopinavir/ritonavir and hydroxychloroquine50UnspecifiedUnspecifiedNot recruitingJapanChiCTR2000030166 (ICTPR)Arm A: lopinavir/ritonavir and interferon alpha 2b and Qing-Wen Bai-Du-Yin granulesArm B: lopinavir/ritonavir and interferon alpha 2b20YesNoNot recruitingChinaChiCTR2000030218 (ICTPR)Arm A: lopinavir/ritonavir and Xiyanping injectionArm B: ritonavir80UnspecifiedUnspecifiedRecruitingChinaNCT04252885 (ClinicalTrials.gov)Arm A: lopinavir/ritonavir + basic treatment (unspecified)Arm B: umifenovir + basic treatment (unspecified)Arm C: basic treatment (unspecified)125YesNoRecruitingChinaNCT04276688 (ClinicalTrials.gov)Arm A: lopinavir/ritonavir + ribavirin + interferon beta 1bArm B: lopinavir/ritonavir70YesNoRecruitingHong KongChiCTR2000029539 (ICTPR)Arm A: lopinavir/ritonavirArm B: standard treatment328YesNoRecruitingChinaChiCTR2000029996 (ICTPR)Arm A: low-dose favipiravirArm B: medium-dose favipiravirArm C: high-dose favipiravir60YesNoRecruitingChinaChiCTR2000029638 (ICTPR)Arm A: nebulised rSIFN-coArm B: nebulised interferon alpha100YesYesRecruitingChinaChiCTR2000029496 (ICTPR)Arm A: Novaferon atomisation inhalationArm B: lopinavir/ritonavirArm C: Novaferon and lopinavir/ritonavir90YesNoRecruitingChinaNCT04303299 (ClinicalTrials.gov)Arm A: oseltamivir and chloroquineArm B: lopinavir/ritonavir and favipiravirArm C: lopinavir/ritonavir and oseltamivirArm D: lopinavir/ritonavir and oseltamivirArm E: favipiravir and lopinavir/ritonavirArm F: darunavir/ritonavir, oseltamivir, and chloroquineArm G: standard treatment80YesNoNot recruitingThailandNCT04302766 (ClinicalTrials.gov)Arm A: remdesivirUnspecifiedUnspecifiedUnspecifiedAvailableUSANCT04292899 (ClinicalTrials.gov)Arm A: remdesivirArm B: standard treatment400YesNoRecruitingUSA and Asia (Gilead)NCT04292730 (ClinicalTrials.gov)Arm A: remdesivirArm B: standard treatment600YesNoRecruitingUSA and Asia (Gilead)NCT04280705 (ClinicalTrials.gov)Arm A: remdesivirArm B: placebo394YesDoubleRecruitingUSA and South Korea2020-000841-15 (EU-CTR)Arm A: remdesivirArm B: standard treatment400YesNoRecruitingWorldwide (Gilead)2020-000842-32 (EU-CTR)Arm A: remdesivirArm B: standard treatment600YesNoRecruitingWorldwide (Gilead)NCT04252664 (ClinicalTrials.gov)Arm A: remdesivirArm B: placebo308YesQuadrupleRecruitingChinaNCT04257656 (ClinicalTrials.gov)Arm A: remdesivirArm B: placebo453YesQuadrupleRecruitingChinaNCT04315948 (ClinicalTrials.gov)Arm A: remdesivirArm B: lopinavir/ritonavirArm C: lopinavir/ritonavir and interferon beta 1aArm D: hydroxychloroquineArm E: standard treatment3100YesNoRecruitingFranceChiCTR2000029387 (ICTPR)Arm A: ribavirin and interferon alpha-1bArm B: lopinavir/ritonavir, and interferon alpha-1bArm C: ribavirin, lopinavir/ritonavir, and interferon alpha-1b108UnspecifiedUnspecifiedRecruitingChinaIRCT20200128046294N2 (ICTPR)Arm A: sofosbuvir/daclatasvirArm B: standard treatment70YesSingleRecruitingIranChiCTR2000029400 (ICTPR)Arm A: traditional Chinese medicineArm B: lopinavir/ritonavirArm C: traditional Chinese medicine and lopinavir/ritonavir60UnspecifiedUnspecifiedRecruitingChinaChiCTR2000030262 (ICTPR)Arm A: type 1 interferon and TFF2 dose 1Arm B: type 1 interferon and TFF2 dose 2Arm C: standard treatment30YesUnspecifiedRecruitingChinaChiCTR2000029573 (ICTPR)Arm A: umifenovirArm B: Novaferon and umifenovirArm C: lopinavir/ritonavirArm D: umifenovirArm E: novaferon and lopinavir/ritonavirArm F: novaferon and umifenovir480YesNoNot recruitingChinaChiCTR2000029621 (ICTPR)Arm A: umifenovirArm B: standard treatment380YesNoRecruitingChinaNCT04254874 (ClinicalTrials.gov)Arm A: umifenovirArm B: umifenovir and pegylated interferon alpha 2b100YesSingleRecruitingChinaNCT04255017 (ClinicalTrials.gov)Arm A: umifenovirArm B: oseltamivirArm C: lopinavir/ritonavir400YesSingleRecruitingChinaChiCTR2000029993 (ICTPR)Arm A: umifenovir and Liushen capsuleArm B: standard treatment40YesNoRecruitingChinaNCT04275388 (ClinicalTrials.gov)Arm A: Xiyanping injection, lopinavir/ritonavir and interferon alpha nebulisationArm B: lopinavir/ritonavir and interfern alpha nebulisation348YesNoNot recruitingChina (Jiangxi Qingfeng Pharmaceutical)AntimalarialChiCTR2000030031 (ICTPR)Arm A: chloroquineArm B: placebo120YesDoubleRecruitingChinaChiCTR2000029988 (ICTPR)Arm A: chloroquineArm B: standard treatment80UnspecifiedUnspecifiedRecruitingChinaChiCTR2000029975 (ICTPR)Arm A: chloroquine10NoUnspecifiedNot recruitingChinaChiCTR2000029939 (ICTPR)Arm A: chloroquineArm B: standard treatment100YesSingleRecruitingChinaChiCTR2000029935 (ICTPR)Arm A: chloroquine100NoUnspecifiedRecruitingChinaChiCTR2000029837 (ICTPR)Arm A: chloroquineArm B: placebo120YesDoubleNot recruitingChinaChiCTR2000029826 (ICTPR)Arm A: chloroquineArm B: placebo45YesDoubleNot recruitingChinaChiCTR2000029542 (ICTPR)Arm A: chloroquineArm B: standard treatment20UnspecifiedUnspecifiedRecruitingChinaChiCTR2000029741 (ICTPR)Arm A: chloroquineArm B: lopinavir/ritonavir112YesNoRecruitingChinaChiCTR2000030718 (ICTPR)Arm A: chloroquineArm B: standard treatment80YesNoRecruitingChinaChiCTR2000029992 (ICTPR)Arm A: chloroquine and hydroxychloroquineArm B: standard treatment100YesNoNot recruitingChinaChiCTR2000030417 (ICTPR)Arm A: chloroquine aerosol inhalationArm B water aerosol inhalation30UnspecifiedUnspecifiedNot recruitingChinaChiCTR2000030082 (ICTPR)Arm A: dihydroartemisinin/piperaquine tablets combined with antiviral treatment (presumed alpha-interferon + umifenovir)Arm B: alpha-interferon + umifenovir40YesNoSuspendedChinaChiCTR2000029898 (ICTPR)Arm A: hydroxychloroquineArm B: chloroquine100YesNoRecruitingChinaNCT04261517 (ClinicalTrials.gov)Arm A: hydroxychloroquineArm B: standard of care30YesNoRecruitingChinaChiCTR2000030054 (ICTPR)Arm A: hydroxychloroquineArm B: standard treatment100YesNoNot recruitingChinaChiCTR2000029868 (ICTPR)Arm A: hydroxychloroquineArm B: standard treatment200YesUnspecified.RecruitingChinaChiCTR2000029740 (ICTPR)Arm A: hydroxychloroquineArm B: standard treatment78YesNoRecruitingChinaChiCTR2000029559 (ICTPR)Arm A: hydroxychloroquineArm B: hydroxychloroquineArm C: placebo300UnspecifiedUnspecifiedRecruitingChina2020-000890-25 (EU-CTR) [17.Gautret P. et al.Hydroxychloroquine and azithromycin as a treatment of COVID-19: preliminary results of an open-label non-randomized clinical trial.Int. J. Antimicrob. Agents. 2020; (Published online March 20, 2020. https://doi.org/10.1016/j.ijantimicag.2020.105949)Crossref PubMed Scopus (3763) Google Scholar]Arm A: hydroxychloroquine25NoNoRecruitingFranceChiCTR2000029899 (ICTPR)Arm A: hydroxychloroquineArm B: chloroquine100YesNoRecruitingChinaNCT04315896 (ClinicalTrials.gov)Arm A: hydroxychloroquineArm B: placebo500YesQuadrupleNot recruitingMexicoNCT04316377 (ClinicalTrials.gov)Arm A: hydroxychloroquineArm B: standard treatment202YesNoNot recruitingNorwayImmunosuppressantsNCT04263402 (ClinicalTrials.gov)Arm A: methylprednisolone (<40 mg/day)Arm B: methylprednisolone (40–80 mg/day)100YesSingleRecruitingChinaChiCTR2000030089 (ICTPR)Arm A: conventional treatment + adalimumabArm B: conventional treatment60YesNoNot yet recruitingChinaChiCTR2000030481 (ICTPR)Arm A: early corticosteroid interventionArm B: middle–late corticosteroid interventionArm C: standard care200YesNoRecruitingChinaNCT04288713 (ClinicalTrials.gov)Arm A: eculizumabUnspecifiedUnspecifiedUnspecifiedAvailableUSANCT04280588 (ClinicalTrials.gov)Arm A: fingolimodArm B: standard treatment30NoNoRecruitingChinaChiCTR2000030703 (ICTPR)Arm A: ixekizumab and antiviral therapyArm B: antiviral therapy40YesSingleRecruitingChinaNCT04275245 (ClinicalTrials.gov) [20.Bian H. et al.Meplazumab treats COVID-19 pneumonia: an open-labelled, concurrent controlled add-on clinical trial.medRxiv. 2020; (Published online March 24, 2020. https://doi.org/10.1101/2020.03.21.20040691)Google Scholar]Arm A: meplazumab20NoNoRecruitingChinaNCT04273321 (ClinicalTrials.gov)Arm A: methylprednisoloneArm B: standard treatment400YesNoRecruitingChinaNCT04244591 (ClinicalTrials.gov)Arm A: methylprednisoloneArm B: standard treatment80YesNoRecruitingChinaChiCTR2000029656 (ICTPR)Arm A: methylprednisoloneArm B: standard treatment100YesNoNot recruitingChinaChiCTR2000029386 (ICTPR)Arm A: methylprednisoloneArm B: standard treatment48YesUnspecifiedRecruitingChinaNCT04315298 (ClinicalTrials.gov)Arm A: sarilumab high doseArm B: sarilumab low doseArm C: placebo400YesQuadrupleRecruitingUSA (Regeneron Pharmaceuticals)ChiCTR2000030058 (ICTPR)Arm A: standard treatment + leflunomideArm B: standard treatment + placebo200YesYesNot yet recruitingChinaChiCTR2000030196 (ICTPR)Arm A: tocilizumab60NoNoNot recruitingChinaChiCTR2000029765 (ICTPR)Arm A: tocilizumabArm B: standard treatment188YesUnspecifiedRecruitingChinaNCT04315480 (ClinicalTrials.gov)Arm A: tocilizumab30NoNoNot recruitingFranceNCT04317092 (ClinicalTrials.gov)Arm A: tocilizumab330NoNoRecruitingItalyChiCTR2000030442 (ICTPR)Arm A: tocilizumab, IVIG, and CCRT100NoUnspecifiedNot recruitingChinaChiCTR2000030580 (ICTPR)Arm A: tozumabdNo literature outside trial protocol; likely tocilizumab. and adalimumabArm B: standard treatment60YesUnspecifiedRecruitingChinaImmune modulatorsNCT04317040 (ClinicalTrials.gov)Arm A: CD24FcArm B: placebo230YesQuadrupleNot recruitingUSA (OncoImmune)ChiCTR2000029776 (ICTPR)Arm A: conventional treatment + polyinosinic-polycytidylic acidArm B: conventional treatment40YesNoRecruitingChinaNCT04299724 (ICTPR)Arm A: Covid-19/aAPC vaccine100NoNoRecruitingChinaChiCTR2000030939 (ICTPR)Arm A: CSA000110YesUnspecifiedRecruitingChinaChiCTR2000030016 (ICTPR)Arm A: inhaled inactive Mycobacterium vaccineArm B: inhaled physiological saline60YesYesRecruitingChinaChiCTR2000030167 (ICTPR)Arm A: interleukin-2Arm B: standard treatment80YesUnspecifiedNot recruitingChinaNCT04261426 (ClinicalTrials.gov)Arm A: IVIGArm B: standard treatment80YesNoNot recruitingChinaNCT04276896 (ICTPR)Arm A: LV-SMENP-DC vaccine and antigen specific cytotoxic T cells100NoNoRecruitingChinaNCT04268537 (ClinicalTrials.gov)Arm A: PD-1-blocking AbArm B: thymosinArm C: standard treatment120YesSingleNot recruitingChinaChiCTR2000030028 (ICTPR)Arm A: PD-1 mAb + standard treatmentArm B: standard treatment40YesNoNot yet recruitingChinaNCT04312997 (ClinicalTrials.gov)Arm A: PUL-042 nebuliserArm B: sterile saline inhaler100YesQuadrupleNot recruitingUSA (Pulmotect)ChiCTR2000030750 (ICTPR)Arm A: recombinant chimeric DC vaccineArm B: normal saline120YesUnspecifiedNot recruitingChinaChiCTR2000030007 (ICTPR)Arm A: standard treatment + rhG-CSFArm B: standard treatment200YesNoNot yet recruitingChinaChiCTR2000029636 (ICTPR)Arm A: standard treatment and vMIP atomised inhalation40NoNoRecruitingChinaChiCTR2000029806 (ICTPR)Arm A: subcutaneous thymosinArm B: camrelizumab infusionArm C: conventional treatment120YesNoRecruitingChinaChiCTR2000030779 (ICTPR)Arm A: ulinastatin (trypsin inhibitor)Arm B: standard treatment100YesNoRecruitingChinaCytokine removalChiCTR2000030475 (ICTPR)Arm A: CytoSorb cytokine removal19NoNoNot recruitingChinaChiCTR2000030477 (ICTPR)Arm A: oXiris membrane19NoNoNot recruitingChinaChiCTR2000030265 (ICTPR)Arm A: oXiris membraneArm B: standard treatment30UnspecifiedUnspecifiedNot recruitingChinaChiCTR2000030835 (ICTPR)Arm A: high-dose MSCsArm B: low-dose MSCs20NoUnspecifiedRecruitingChinaChiCTR2000029817 (ICTPR)Arm A: high-dose NK cells and MSCsArm B: conventional-dose NK cells and MSCsArm C: preventive-dose NK cells and MSCs60UnspecifiedUnspecifiedNot recruitingChina (Guangchou Reborn Health Management Co)ChiCTR2000029606 (ICTPR)Arm A: menstrual blood-derived stem cellsArm B: artificial liver therapyArm C: artificial liver therapy and menstrual blood-derived stem cellsArm D: standard treatment73UnspecifiedUnspecifiedRecruitingChinaNCT04315987 (ClinicalTrials.gov)Arm A: MSCs24NoNoNot recruitingBrazil (Cellavita Pesquisa Cientifica Ltd)NCT04276987 (ClinicalTrials.gov)Arm A: MSC-derived exosomes30NoNoNot recruitingChina (Cellular Biomedicine Group)NCT04288102 (ClinicalTrials.gov)Arm A: MSCsArm B: placebo60YesQuadrupleRecruitingChinaNCT04252118 (ClinicalTrials.gov)Arm A: MSCsArm B: standard treatment20NoNoRecruitingChina (IPM, Vcanbio Cell and Gene Engineering)ChiCTR2000030300 (ICTPR)Arm A: MSCs9NoUnspecifiedRecruitingChinaChiCTR2000030224 (ICTPR)Arm A: MSCsArm B: normal saline32UnspecifiedUnspecifiedNot recruitingChinaChiCTR2000030173 (ICTPR)Arm A: MSCsArm B: standard treatment60UnspecifiedUnspecifiedNot recruitingChina (Hunan yuanpin Cell Biotech)ChiCTR2000030020 (ICTPR)Arm A: MSCs20NoNoRecruitingChinaChiCTR2000029990 (ICTPR) [22.Leng Z. et al.Transplantation of ACE2-mesenchymal stem cells improves the outcome of patients with COVID-19 pneumonia.Aging Dis. 2020; 11: 216Crossref PubMed Scopus (916) Google Scholar]Arm A: MSCsArm B: saline120YesUnspecifiedRecruitingChinaChiCTR2000030261 (ICTPR)Arm A: MSC-derived exosomesArm B: standard treatment26UnspecifiedUnspecifiedNot recruitingChinaNCT04280224 (ClinicalTrials.gov)Arm A: NK cellsArm B: standard treatment30YesNoRecruitingChinaChiCTR2000030509 (ICTPR)Arm A: NK cellsArm B: electrolyte injection40UnspecifiedUnspecifiedNot recruitingChinaChiCTR2000030944 (ICTPR)Arm A: NK cells and MSCArm B: standard treatment20YesNoNot recruitingChinaNCT04302519 (ClinicalTrials.gov)Arm A: pulp MSCs24NoNoNot recruitingChina (CAR-T Biotechnology Co, Ltd)ChiCTR2000029580 (ICTPR)Arm A: ruxolitinib and MSCsArm B: standard treatment70YesSingleRecruitingChinaNCT04299152 (ClinicalTrials.gov)Arm A: stem cell educator therapyArm B: standard treatment20YesSingleNot recruitingUSA (Tianhe Stem Cell Biotechnologies Inc)ChiCTR2000030329 (ICTPR)Arm A: umbilical cord blood CIK cellsArm B umbilical cord NK cellsArm C: standard treatment90UnspecifiedUnspecifiedNot recruitingChinaChiCTR2000029812 (ICTPR)Arm A: umbilical cord blood mononuclear cell preparationsArm B: standard treatment60UnspecifiedUnspecifiedNot recruitingChina (Guangzhou Reborn Health Management Consultation Co)ChiCTR2000029572 (ICTPR)Arm A: umbilical cord blood mononuclear cellsArm B: standard treatment30YesUnspecifiedRecruitingChinaChiCTR2000029818 (ICTPR)Arm A: umbilical cord blood plasma preparationsArm B: standard treatment60UnspecifiedUnspecifiedNot recruitingChina (Guangzhou Reborn Health Management Consultation Co)NCT04293692 (ClinicalTrials.gov)Arm A: umbilical cord MSCsArm B: placebo48YesTripleWithdrawnChina (Wuhan Hamilton Biotechnology)NCT04273646 (ClinicalTrials.gov)Arm A: umbilical cord MSCsArm B: placebo48YesNoNot recruitingChina (Wuhan Biotechnology)NCT04269525 (ClinicalTrials.gov)Arm A: umbilical cord MSCs10NoNoRecruitingChina (Tuohua Biological Technology Co)ChiCTR2000030138 (ICTPR)Arm A: umbilical cord MSCsArm B: placebo60YesDoubleNot recruitingChinaChiCTR2000030484 (ICTPR)Arm A: umbilical cord MSCsArm B: umbilical cord MSCs and derived exosomesArm C: placebo120UnspecifiedUnspecifiedNot recruitingChinaChiCTR2000030116 (ICTPR)Arm A: umbilical cord MSCs dose AArm B umbilical cord MSCs dose B16YesUnspecifiedRecruitingChinaChiCTR2000029816 (ICTPR)Arm A: umbilical cord MSCsArm B: standard treatment60YesNoNot recruitingChina (Guangzhou Reborn Health Management)NCT04313322 (ClinicalTrials.gov)Arm A: Wharton jelly MSCs5NoNoRecruitingJordan (Stem Cells Arabia)ChiCTR2000030088 (ICTPR)Arm A: Wharton jelly MSCsArm B: saline20YesUnspecifiedNot recruitingChinaPlasma-based therapyChiCTR2000030702 (ICTPR)Arm A: convalescent plasma therapyArm B: standard treatment50YesNoRecruitingChinaChiCTR2000030046 (ICTPR)Arm A: anti-2019-nCoV virus inactivated plasma10NoNoRecruitingChinaChiCTR2000030381 (ICTPR)Arm A: anti-SARS-CoV-2 inactivated convalescent plasmaArm B: ordinary plasma40YesNoNot recruitingChinaChiCTR2000030010 (ICTPR)Arm A: anti-SARS-CoV-2 virus inactivated plasmaArm B: ordinary plasma100YesDoubleNot recruitingChinaChiCTR2000030841 (ICTPR)Arm A: convalescent immunoglobulinArm B: gamma-globulin10NoNoRecruitingChinaNCT04264858 (ClinicalTrials.gov)Arm A: convalescent immunoglobulinArm B: gamma globulin10NoNoNot recruitingChinaChiCTR2000030039 (ICTPR)Arm A: convalescent plasmaArm B: standard treatment90NoNoRecruitingChinaChiCTR2000029850 (ICTPR)Arm A: convalescent plasmaArm B: standard treatment20NoUnspecifiedRecruitingChinaChiCTR2000