COVID-19Phase 2/3Bari-SolidActNCT04891133
EU SolidAct: An Adaptive Pandemic and Emerging Infection Platform Trial
A Phase 2/3 study testing Baricitinib in people with COVID-19 and Emerging Infectious Disease, run by Oslo University Hospital at 92 sites in 15 countries.
Trial summary
EU SolidAct is a randomized, multifactorial, adaptive platform trial for COVID-19 and emerging infectious diseases and pandemics. The purpose of this study is to evaluate the effect of a range of interventions to improve outcome of patients admitted to hospital with COVID-19. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19, Emerging Infectious Disease
- What is being tested?
- Baricitinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 290 participants
- Where
- 92 sitesin 15 countries
- Study dates
- 3 Jun 2021to 23 Jan 2023
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- Participants are excluded from the study if any of the following general exclusion criteria (GE) apply:
- GE1. Anticipated transfer to another non-trial hospital within 72 hours
- Additional exclusion criteria, including prohibited medication, confounding trials and details on contraception and pregnancy are given in the intervention-specific sub-protocols
- SE-01. Patients receiving Janus kinase (JAK) inhibitors (including baricitinib) for any indication at screening.
- SE-20. Have received tocilizumab or sarilumab for any indication 4 weeks prior to screening.
- Note: Tocilizumab as rescue therapy will be allowed in patients with clinical progression after inclusion, see section 6.8 concomitant medication. If tocilizumab or other immunosuppressive rescue therapy is started, IMP should be discontinued.
Show all 29Show fewer
- SE-21. Patients with recent changes in immunosuppressive therapy that could interfere with the potential effect of baricitinib.
- Note: An assessment of the total level of immunosuppression, hematological parameters (SE-13 and SE-14), drug half-lives, drug-drug interactions, and underlying medical conditions (SE-22) must be performed as part of the risk/benefit evaluation.
- Recipients of bone marrow transplant or solid organ transplant last 6 months, or with transplant rejection last 6 months, should not be included.
- Organ transplant recipients receiving triple immunosuppression can only be included if the anti-metabolite (mycophenolic acid or mTOR inhibitor) has been temporarily discontinued per clinical practice10. IMP should be discontinued once triple immunosuppression is restarted.
- SE-22. Any medical condition that in the opinion of the investigator poses an inacceptable risk of serious infection or aggravation of the medical condition by participating in the trial.
- Note: Patients with acute leukemia or history of lymphoma should not be included. Cancer patients under active treatment, HIV positive individuals with detectable HIV-RNA, or other patient group associated with high risk of serious infection or aggravation of the medical condition should only be included if, in the judgement of the investigator, the potential benefit outweighs the potential risk.
- SE-03. Have received dexamethasone 6 mg daily (or alternative regimens with equivalent of corticosteroids) for more than 4 days prior to screening as part of SoC for severe/critical COVID-19
- SE-04. Had COVID-related symptoms > 21 days or hospitalized > 7 days.
- SE-05. Strong inhibitors of organic anion transporter 3 [OAT3] (e.g., probenecid) that cannot be discontinued at study entry.
- SE-07. Have received any live vaccine within 4 weeks before screening, or intend to receive a live vaccine during the study (until day 90 (+/- 14 days)).
- Note: Use of non-live (inactivated) vaccinations, including COVID-19 vaccinations, is allowed for all participants.
- SE-08. Are using or will use extracorporeal blood purification (EBP) device to remove proinflammatory cytokines from the blood such as a cytokine absorption or filtering device, for example, CytoSorb®.
- SE-09. Have diagnosis of current active tuberculosis (TB) or, if known, latent TB treated for less than 4 weeks with appropriate anti-tuberculosis therapy per local guidelines (by history only, no screening tests required).
- SE-10. Suspected serious, active bacterial, fungal, viral, or other infection (besides COVID-19) that in the opinion of the investigator could constitute a risk when taking investigational product.
- SE-12. Have a history of venous thromboembolism (VTE) (deep vein thrombosis [DVT] and/or pulmonary embolism [PE]) within 12 weeks prior to randomization or have a history of recurrent (>1) VTE (DVT/PE).
- SE-13. Neutropenia (absolute neutrophil count <1000 cells/microliters).
- SE-14. Lymphopenia (absolute lymphocyte count <200 cells/microliters).
- SE-15. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >5 times ULN.
- SE-16. Subjects with estimated glomerular filtration rate (eGFR) (Modification of Diet in Renal Disease [MDRD]) <30 millilitre/minute/1.73 meters squared are excluded.
- SE-17. Known hypersensitivity to baricitinib or any of its excipients.
- SE-18. Are pregnant or breastfeeding, or intend to become pregnant or breastfeed during the study.
- Note: Women of child bearing potential (WOCBP) can only be included based on a negative pregnancy test and WOCBP must comply with requirements regarding highly effective contraception. Refer to section 10.1 for contraception requirements.
- SE-19 Participation in any therapeutic clinical trials investigating immunomodulators for COVID-19
Trial locations and contacts
92 sites in 15 countries.
92 sites in 15 countries
Italy17 sites
Ospedale Santa Maria Annunziata, Malattie Infettive
Bagno a Ripoli, 50012
ASST - Spedali Civili di Brescia - University of Brescia
Brescia, 25123
ATS Sardegna - PO SS Trinità, U.O.C. Malattie Infettive
Cagliari, 09121
Azienda Opsedaliera Universitaria Mater Domini, U.O. Malattie Infettive e Tropicali
Catanzaro, 88100
ASL Frosinone - Ospedale Fabrizio Spaziani, U.O.C. Medicina Interna
Frosinone, 03100
Ospedale S.M. Goretti di Latina, U.O.C. Malattie Infettive
Latina, 04100
Ospedale Mater Salutis di Legnago, U.O.C. di Pneumologia
Legnano, 37045
Ospedale Mater Salutis di Legnago, U.O.S. di Malattie Infettive
Legnano, 37045
ASST Santi Paolo e Carlo, S.C. Malattie Infettive
Milan, 20142
Azienda Ospedaliera Universitaria Vanvitelli, U.O.C. Malattie Infettive
Naples, 80138
AOU Policlinico "P. Giaccone", U.O.C. Malattie Infettive
Palermo, 90127
Azienda Ospedaliera Ospedali Riuniti Marche Nord, U.O.C. Malattie Infettive
Pesaro, 61122
ASL Taranto - Ospedale Oncologico San Giuseppe Moscati, U.O.C. Pneumologia
Taranto, 74010
AOU Città della Salute e Scienza Presidio Molinette
Torino, 10126
Azienda Sanitaria Universitaria Giuliano Isontina (ASU GI), S.C. Malattie Infettive
Trieste, 34128
IRCCS Ospedale Sacro Cuore Don Calabria, U.O.S. Malattie Infettive e Tropicali
Verona, 37024
Azienda Ospedaliera Universitaria Integrata di Verona, U.O.C. Malattie Infettive e Tropicali
Verona, 37314
France16 sites
CHU Amiens Picardie (ICU)
Amiens, 80054
CHU Amiens Picardie (ID)
Amiens, 80054
CHU de Bordeaux / Hopital Pellegrin (ICU)
Bordeaux, 33076
CHU de Bordeaux / Hopital Pellegrin (ID)
Bordeaux, 33076
Louis Mourier (ID)
Colombes, 92700
Lous Mourier (ICU)
Colombes, 92700
CHU François Mitterrand
Dijon, 21000
CHU Lille - Hopital Roger Salengro -Pôle Rèanimaition
Lille, 59037
Hopital de la Croix - Rousse - HCL (ICU)
Lyon, 69004
Hopital de la Croix - Rousse - HCL (ID)
Lyon, 69004
GHRMSA Hopital Emile Muller (ICU)
Mulhouse, 68100
GHRMSA Hopital Emile Muller (IM)
Mulhouse, 68100
Hôpital Saint-Antoine (ICU)
Paris, 75012
Hôpital Saint-Antoine (ID)
Paris, 75012
Hôpital Bichat - Claude Bernard (ICU)
Paris, 75017
Hôpital Bichat - Claude Bernard (ID)
Paris, 75017
Norway10 sites
Drammen (Vestre Viken) Hospital
Drammen, NO-3004
Østfold sykehuset i Kalnes
Grålum, 1714
Akershus Universitetssykehus
Lørenskog, 1478
Lovisenberg Diaconal Hospital
Oslo, 04400
OUS Ullevål
Oslo, N-0424
Bærum Hospital
Sandvika, 1346
Stavanger University Hospital
Stavanger, 4011
Vestfold Hospital
Tønsberg, 3103
University Hospital North Norway
Tromsø, 9019
St. Olavs Hospital
Trondheim, 7006
Ireland8 sites
Cork University Hospital
Cork, T12 DFK4
St Vincent's University Hospital
Dublin, 4
Mater Misericordiae University Hospital
Dublin, D07 R2WY
St James's Hospital, Dublin
Dublin, D08 NHY1
Beaumont Hospital, Dublin
Dublin, D09VZNO
Tallaght University Hospital
Dublin, D24 NR0A
University Hospital Galway
Galway, H91 YR71
University Hospital Limerick
Limerick, V94 F858
Portugal8 sites
CHMT - Centro Hospitalar do Médio Tejo- Hospital de Abrantes
Abrantes, 2200-202
CHUC - Centro Hospitalar e Universitário de Coimbra
Coimbra, 3000-075
CHUA-Faro - Centro Hospitalar Universitário do Algarve
Faro
CHLC-HCC - Hospital Curry Cabral, Centro Hospitalar Universitário Lisboa Central
Lisbon, 1050-099
CHLO - Centro Hospitalar de Lisboa Ocidental - HEM and HSFX
Lisbon, 1349-019
CHSJ - São João Hospital Center
Lisbon, 1349-019
CHLN - Centro Hospitalar Universitário Lisboa Norte
Lisbon, 1649-035
HBA - Hospital Beatriz Ângelo
Loures, 2674-514
Spain8 sites
Hospital Universitario Reina Sofia
Córdoba, 14004
Hospital Universitario de Jaen
Jaén, 23001
Hospital Universitario La Paz
Madrid, 28046
Hospital Virgen de la Victoria
Málaga, 29101
Hospital Costa del Sol
Marbella, 29603
Hospital Universitario Virgen Macarena
Seville, 41009
Hospital Universitario Virgen del Rocio
Seville, 41013
Hospital Universitario Virgen de Valme
Seville, 41014
Slovakia5 sites
University Hospital Bratislava, Kramare
Bratislava, 83105
University Hospital Martin
Martin, 036 01
Nsp Trebisov, Svet Zdravia a.s.
Trebišov, 075 01
Faculty Hospital Trencin
Trenčín, 91171
University Hospital Trnava
Trnava, 917 75
Turkey (Türkiye)5 sites
Hacettepe Üniversitesi Tıp Fakültesi, İnfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı (Site 1)
Ankara, 06230
Hacettepe Üniversitesi Tıp Fakültesi, İnfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı (Site 2)
Ankara, 06230
Ankara Üniversitesi Tıp Fakültesi, Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı
Ankara
İstanbul Üniversitesi İstanbul Tıp Fakültesi, Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı
Istanbul
Dokuz Eylül Üniversitesi Tıp Fakültesi Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı
Izmir, 35340
Austria3 sites
Medical University of Innsbruck (University Hospital for Neurosurgery)
Innsbruck, 6020
Medical Unversity of Innsbruck (Joint Institute for Emergency Medicine and Critical Care)
Innsbruck, 6020
Medical Unversity of Innsbruck (University Hospital for Anaesthesia and Intensive Care)
Innsbruck, 6020
Belgium3 sites
Erasme Hospital
Brussels, 1070
UZ Brussel
Brussels, 1090
Cliniques Universitaires Saint-Luc
Brussels, 1200
Hungary3 sites
University of Debrecen (Clinic for Infectology)
Debrecen, 4031
University of Pécs
Pécs, 7623
University of Szeged (Pandemic Clinics)
Szeged, 6725
Germany2 sites
Gesundheit Nord gGmbH (GeNo)
Bremen, 28177
Technische Universität München (TUM) - Klinikum rechts der Isar
München, 81675
Greece2 sites
Evangelismos Hospital
Athens, 10675
Attikon University Hospital
Athens, 12462
About this study
Official title: European DisCoVeRy for Solidarity: An Adaptive Pandemic and Emerging Infection Platform Trial
EU SolidAct is a randomized, multifactorial, adaptive platform trial for COVID-19 and emerging infectious diseases and pandemics. The purpose of this study is to evaluate the effect of a range of interventions to improve outcome of patients admitted to hospital with COVID-19. The platform is designed for running phase 2 and phase 3 trials, and with modular data capture (end point/safety data, biobanking, add-on studies) depending on the capacity of participating sites. The study consists of two parts with different primary end points depending on disease stage: EU SolidAct part A includes hospitalized patients with moderate disease, whereas EU SolidAct part B includes hospitalized patients with severe and critical disease.
Read the detailed description
There is an urgent need for developing an adaptive pan-European research platform for rapid and coordinated investigation of new candidate drugs during ongoing pandemics. EU-SolidAct is an Adaptive Platform Trial master protocol developed for evaluating drug interventions in hospitalized patients with COVID-19. While this master protocol is developed for therapeutic interventions in hospitalized patients, it could also form the basis for trial protocols on other interventions and/or in non-hospitalized populations. The protocol is additionally developed to facilitate a joint European response to the challenge of evaluating interventions during future epidemics. The described disease states and endpoints may need to be adapted to the epidemic in question.
EU-SolidAct is a European, multicentre, randomized, parallel, phase 2 and 3 platform trial on drug interventions, both new and repurposed, single or in combination, in hospitalized adult patients with moderate or severe COVID-19, as defined by the WHO Working Group on the Clinical Characterisation and Management of COVID-191. Participants with moderate disease (WHO score 4-5) will be eligible for EU-SolidAct Part A, whereas participants with severe/critical disease (WHO score 6-9) will be eligible for EU-SolidAct Part B. This might include participants progressing from Part A.
In Part A of phase 3 confirmatory trials, the primary objective is to determine the effect of therapeutic interventions on occurrence of disease progression, from moderate disease to severe/critical disease or death within 14 days. In Part B, the primary objective is to determine the effect of therapeutic interventions on occurrence of death within 60 days.
In phase 2 the default objective for both parts is to explore the effect of the therapeutic intervention on respiratory dysfunction at day 5. Other objectives, e.g. effect on virological outcomes may be considered based on the treatment mode of action.
In phase 3 trials, both superiority and non-inferiority hypotheses may be evaluated. In phase 2 trials, only superiority hypotheses will be evaluated. In addition to single treatments, combination of treatments could also be assessed through factorial design. EU-SolidAct is designed to be adaptive and to enable inclusion of hospitals in Europe and beyond, regardless of epidemic waves and available resources. This requires the master protocol to be modular, ranging from a core set of outcomes to more advanced data capture. Hospitals will access the study on different pre-set levels, ranging from a core set of clinical endpoints and safety measures, to a more advanced level with biobanking and possibilities for add-on studies
- Conditions
- COVID-19, Emerging Infectious Disease
- Being tested
- Baricitinib, Placebo
- Medical subject headings
- COVID-19, Communicable Diseases, Emerging
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BaricitinibDrug
Also called Olumiant
4 mg baricitinib (2 tablets of 2 mg) once daily
PlaceboDrug
4 mg placebo (2 tablets of 2 mg) once daily
| Study group | Role | What they receive |
|---|---|---|
| Active arm | Experimental | 4mg Baricitinib up to 14 days + SoC Receives: Drug: Baricitinib |
| Comparator | Placebo comparator | Matching placebo up to 14 days + SoC Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurrence of death within 60 days (primary end point, EU SolidAct part B)
The primary outcome for phase 3 trials in EU SolidAct part B is occurrence of death within 60 days
Measured: 60 days
Occurrence of disease progression within 14 days (primary end point, EU SolidAct part A)
The primary outcome for phase 3 trials in EU SolidAct part A is occurrence of disease progression, defined as a progression of disease state from moderate (WHO score 4-5) to severe/critical (WHO score 6-9) or death (WHO score 10)
Measured: 14 days
SpO2/FiO2-ratio at day 5 (primary end point, phase 2 trials)
In phase 2 exploratory trials, the default primary objective for both part A and B is to explore the effect of the intervention on respiratory dysfunction assessed by SpO2/FiO2-ratio at day 5
Measured: 5 days
Secondary outcomes (9)
Occurrence of disease progression within 28 days (shared secondary end point for part A and B)
Occurrence of disease progression, defined as a progression of disease state from moderate (WHO score 4-5) to severe/critical/death (WHO score 6-10) or from severe/critical (WHO score 6-9) to death
Measured: 28 days
Time to sustained recovery (shared secondary end point for part A and B)
Time from randomization to sustained recovery, defined as being discharged from the index hospitalization, followed by being alive and at home for 14 consecutive days within 90 days
Measured: 90 days
Time to first hospital discharge (shared secondary end point for part A and B)
Time from randomization to first hospital discharge within 90 days
Measured: 90 days
Disease state at Day 15 and Day 29 (shared secondary end point for part A and B)
Disease state on a 5-point scale defined as:
- Mild (WHO score 1-3) or better,
- Moderate (WHO score 4-5),
- Severe (WHO score 6),
- Critical (WHO score 7-9) or
- Death at Day 15 and 29
Measured: 28 days
Time from randomization to recovery (shared secondary end point for part A and B)
Time from randomization to recovery defined as no need for oxygen
Measured: 90 days
SpO2/FiO2-ratio at Day 3, 5 and 8 (shared secondary end point for part A and B)
Respiratory dysfunction assessed by SpO2/FiO2-ratio at Day 3, 5 and 8
Measured: 8 days
Viral clearance during hospitalization (shared secondary end point for part A and B)
Viral clearance as assessed by SARS-CoV-2 PCR in naso/oropharyngeal specimens collected at Days 1, 3, 5, 8 and 15 (± 1 day, except baseline) if still hospitalized
Measured: Days 1, 3, 5, 8 and 15
Occurrence of serious adverse events within 90 days (shared secondary end point for part A and B)
Occurrence of serious adverse events leading to study treatment discontinuation or death
Measured: 90 days
Patient related outcomes at day 90 (shared secondary end point for part A and B)
The Oslo COVID-19 QLQ-PW80 subscale scores at Day 90
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2021
- Study start3 Jun 2021
- Primary completion15 Dec 2022
- Study completion23 Jan 2023
Why it stopped: The trial was stopped prematurely due to external evidence that arose during the study period showing that the IMP, baricitinib, was not effective in the primary study population.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for COVID-19Studies of the same condition, open and under way.
- More trials run by Oslo University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 290 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oslo University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Institut National de la Santé Et de la Recherche Médicale, France, Epidemiological and Clinical Research Information Network
- Responsible party
- Principal investigator, Marius Trøseid, Oslo University Hospital
- Investigators
- Domique Costagliola, PhD, Study chair, Institut National de la Santé Et de la Recherche Médicale, FranceJose R Arribas, MD PhD, Principal investigator, Hospital Universario La Paz, Madrid
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04891133
- Sponsor's protocol ID
- EU SolidAct
- Other IDs
- 2022-500385-99-00
- Acronym
- Bari-SolidAct
- Status last verified
- Feb 2023
- First submitted
- 7 May 2021
- Last updated
- 6 Feb 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual patient-level data will be made as public as possible while maintaining the integrity and privacy of the trial participants. Anonymized data will be made publicly available using a data repository, including any programming code used to produce the trial results. De-identified data will be made available upon request and evaluation of the requestee's ability and willingness to maintain the integrity and privacy of the trial participants. Further details of data sharing will be given in a separate data sharing plan.
Publications
Troseid M, Arribas JR, Assoumou L, Holten AR, Poissy J, Terzic V, Mazzaferri F, Bano JR, Eustace J, Hites M, Joannidis M, Paiva JA, Reuter J, Puntmann I, Patrick-Brown TDJH, Westerheim E, Nezvalova-Henriksen K, Beniguel L, Dahl TB, Bouscambert M, Halanova M, Peterfi Z, Tsiodras S, Rezek M, Briel M, Unal S, Schlegel M, Ader F, Lacombe K, Amdal CD, Rodrigues S, Tonby K, Gaudet A, Heggelund L, Mootien J, Johannessen A, Moller JH, Pollan BD, Tveita AA, Kildal AB, Richard JC, Dalgard O, Simensen VC, Balde A, de Gastines L, Del Alamo M, Aydin B, Lund-Johansen F, Trabaud MA, Diallo A, Halvorsen B, Rottingen JA, Tacconelli E, Yazdanpanah Y, Olsen IC, Costagliola D; EU SolidAct study group. Efficacy and safety of baricitinib in hospitalized adults with severe or critical COVID-19 (Bari-SolidAct): a randomised, double-blind, placebo-controlled phase 3 trial. Crit Care. 2023 Jan 10;27(1):9. doi: 10.1186/s13054-022-04205-8.
PubMed 36627655Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.
PubMed 34473343
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- European DisCoVeRy for Solidarity: An Adaptive Pandemic and Emerging Infection Platform Trial
- ClinicalTrials.gov ID
- NCT04891133
- Acronym / sponsor ID
- Bari-SolidAct / EU SolidAct
- Conditions
- COVID-19, Emerging Infectious Disease
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The trial was stopped prematurely due to external evidence that arose during the study period showing that the IMP, baricitinib, was not effective in the primary study population.
- Enrolment
- 290 participants (actual)
- Lead sponsor
- Oslo University HospitalUniversity, hospital or other
- Collaborators
- Institut National de la Santé Et de la Recherche Médicale, France, Epidemiological and Clinical Research Information Network
- Study start
- 3 Jun 2021 (actual)
- Primary completion
- 15 Dec 2022 (actual)
- Study completion
- 23 Jan 2023 (actual)
- First posted
- 18 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
EU SolidAct is a randomized, multifactorial, adaptive platform trial for COVID-19 and emerging infectious diseases and pandemics. The purpose of this study is to evaluate the effect of a range of interventions to improve outcome of patients admitted to hospital with COVID-19. The platform is designed for running phase 2 and phase 3 trials, and with modular data capture (end point/safety data, biobanking, add-on studies) depending on the capacity of participating sites. The study consists of two parts with different primary end points depending on disease stage: EU SolidAct part A includes hospitalized patients with moderate disease, whereas EU SolidAct part B includes hospitalized patients with severe and critical disease.
Detailed description
There is an urgent need for developing an adaptive pan-European research platform for rapid and coordinated investigation of new candidate drugs during ongoing pandemics. EU-SolidAct is an Adaptive Platform Trial master protocol developed for evaluating drug interventions in hospitalized patients with COVID-19. While this master protocol is developed for therapeutic interventions in hospitalized patients, it could also form the basis for trial protocols on other interventions and/or in non-hospitalized populations. The protocol is additionally developed to facilitate a joint European response to the challenge of evaluating interventions during future epidemics. The described disease states and endpoints may need to be adapted to the epidemic in question.
EU-SolidAct is a European, multicentre, randomized, parallel, phase 2 and 3 platform trial on drug interventions, both new and repurposed, single or in combination, in hospitalized adult patients with moderate or severe COVID-19, as defined by the WHO Working Group on the Clinical Characterisation and Management of COVID-191. Participants with moderate disease (WHO score 4-5) will be eligible for EU-SolidAct Part A, whereas participants with severe/critical disease (WHO score 6-9) will be eligible for EU-SolidAct Part B. This might include participants progressing from Part A.
In Part A of phase 3 confirmatory trials, the primary objective is to determine the effect of therapeutic interventions on occurrence of disease progression, from moderate disease to severe/critical disease or death within 14 days. In Part B, the primary objective is to determine the effect of therapeutic interventions on occurrence of death within 60 days.
In phase 2 the default objective for both parts is to explore the effect of the therapeutic intervention on respiratory dysfunction at day 5. Other objectives, e.g. effect on virological outcomes may be considered based on the treatment mode of action.
In phase 3 trials, both superiority and non-inferiority hypotheses may be evaluated. In phase 2 trials, only superiority hypotheses will be evaluated. In addition to single treatments, combination of treatments could also be assessed through factorial design. EU-SolidAct is designed to be adaptive and to enable inclusion of hospitals in Europe and beyond, regardless of epidemic waves and available resources. This requires the master protocol to be modular, ranging from a core set of outcomes to more advanced data capture. Hospitals will access the study on different pre-set levels, ranging from a core set of clinical endpoints and safety measures, to a more advanced level with biobanking and possibilities for add-on studies
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active arm | Experimental | Drug: Baricitinib4mg Baricitinib up to 14 days + SoC |
| Comparator | Placebo comparator | Drug: PlaceboMatching placebo up to 14 days + SoC |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (29 listed)
- Participants are excluded from the study if any of the following general exclusion criteria (GE) apply:
- GE1. Anticipated transfer to another non-trial hospital within 72 hours
- Additional exclusion criteria, including prohibited medication, confounding trials and details on contraception and pregnancy are given in the intervention-specific sub-protocols
- Note: Tocilizumab as rescue therapy will be allowed in patients with clinical progression after inclusion, see section 6.8 concomitant medication. If tocilizumab or other immunosuppressive rescue therapy is started, IMP should be discontinued.
- SE-21. Patients with recent changes in immunosuppressive therapy that could interfere with the potential effect of baricitinib.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BaricitinibAlso: Olumiant4 mg baricitinib (2 tablets of 2 mg) once daily | Drug | Active arm |
| Placebo4 mg placebo (2 tablets of 2 mg) once daily | Drug | Comparator |
Primary outcome
Occurrence of death within 60 days (primary end point, EU SolidAct part B)
Time frame: 60 days
The primary outcome for phase 3 trials in EU SolidAct part B is occurrence of death within 60 days
Occurrence of disease progression within 14 days (primary end point, EU SolidAct part A)
Time frame: 14 days
The primary outcome for phase 3 trials in EU SolidAct part A is occurrence of disease progression, defined as a progression of disease state from moderate (WHO score 4-5) to severe/critical (WHO score 6-9) or death (WHO score 10)
SpO2/FiO2-ratio at day 5 (primary end point, phase 2 trials)
Time frame: 5 days
In phase 2 exploratory trials, the default primary objective for both part A and B is to explore the effect of the intervention on respiratory dysfunction assessed by SpO2/FiO2-ratio at day 5
9 secondary outcomes
Occurrence of disease progression within 28 days (shared secondary end point for part A and B)
Time frame: 28 days
Time to sustained recovery (shared secondary end point for part A and B)
Time frame: 90 days
Time to first hospital discharge (shared secondary end point for part A and B)
Time frame: 90 days
Disease state at Day 15 and Day 29 (shared secondary end point for part A and B)
Time frame: 28 days
Time from randomization to recovery (shared secondary end point for part A and B)
Time frame: 90 days
SpO2/FiO2-ratio at Day 3, 5 and 8 (shared secondary end point for part A and B)
Time frame: 8 days
Viral clearance during hospitalization (shared secondary end point for part A and B)
Time frame: Days 1, 3, 5, 8 and 15
Occurrence of serious adverse events within 90 days (shared secondary end point for part A and B)
Time frame: 90 days
Patient related outcomes at day 90 (shared secondary end point for part A and B)
Time frame: 90 days
Results and safety
The study was stopped early (reason given: The trial was stopped prematurely due to external evidence that arose during the study period showing that the IMP, baricitinib, was not effective in the primary study population.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2023.
- Results publication: PubMed 36627655Troseid M, Arribas JR, Assoumou L, Holten AR, Poissy J, Terzic V, Mazzaferri F, Bano JR, Eustace J, Hites M, Joannidis M, Paiva JA, Reuter J, Puntmann I, Patrick-Brown TDJH, Westerheim E, Nezvalova-Henriksen K, Beniguel L, Dahl TB, Bouscambert M, Halanova M, Peterfi Z, Tsiodras S, Rezek M, Briel M, Unal S, Schlegel M, Ader F, Lacombe K, Amdal CD, Rodrigues S, Tonby K, Gaudet A, Heggelund L, Mootien J, Johannessen A, Moller JH, Pollan BD, Tveita AA, Kildal AB, Richard JC, Dalgard O, Simensen VC, Balde A, de Gastines L, Del Alamo M, Aydin B, Lund-Johansen F, Trabaud MA, Diallo A, Halvorsen B, Rottingen JA, Tacconelli E, Yazdanpanah Y, Olsen IC, Costagliola D; EU SolidAct study group. Efficacy and safety of baricitinib in hospitalized adults with severe or critical COVID-19 (Bari-SolidAct): a randomised, double-blind, placebo-controlled phase 3 trial. Crit Care. 2023 Jan 10;27(1):9. doi: 10.1186/s13054-022-04205-8.
- Derived from this study: PubMed 34473343Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.
- Individual participant dataSharing planned: Yes. Individual patient-level data will be made as public as possible while maintaining the integrity and privacy of the trial participants. Anonymized data will be made publicly available using a data repository, including any programming code used to produce the trial results. De-identified data will be made available upon request and evaluation of the requestee's ability and willingness to maintain the integrity and privacy of the trial participants. Further details of data sharing will be given in a separate data sharing plan.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Domique Costagliola, PhD study chair
Institut National de la Santé Et de la Recherche Médicale, France
Jose R Arribas, MD PhD principal investigator
Hospital Universario La Paz, Madrid
92 sites in 15 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Baricitinib in people with COVID-19 and Emerging Infectious Disease, run by Oslo University Hospital at 92 sites in 15 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 6 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 92 sites in Italy, France, Norway, Ireland, Portugal and 10 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The trial was stopped prematurely due to external evidence that arose during the study period showing that the IMP, baricitinib, was not effective in the primary study population.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Occurrence of death within 60 days (primary end point, EU SolidAct part B) (time frame: 60 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04891133, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2023.