EU SolidAct: An Adaptive Pandemic and Emerging Infection Platform Trial (Bari-SolidAct)
COVID-19, Emerging Infectious Disease
About this trial
This is an interventional treatment trial for COVID-19
Eligibility Criteria
**EU SOLIDACT PLATFORM INCLUSION CRITERIA**:
Participants are eligible to be included in the study only if all the following general inclusion (GI) criteria apply:
- GI1. ≥ 18 years of age
- GI2. Laboratory-confirmed SARS-CoV-2 infection (new infection or reinfection) as determined by PCR not more than 14 days old.
- GI3. Admitted to hospital
- GI4. Informed consent by the participant or legally authorized representative
- GI5A (SolidAct part A): Moderate disease state defined as hospitalised patients without oxygen therapy or oxygen by mask or nasal prongs needed, or
GI5B (SolidAct part B): Severe/critical disease state defined as fulfilling at least one of the following criteria:
- SpO2<90% on room air, or
- SpO2 90-94% with a downwards trend and/or signs of respiratory distress*, or
- Need of oxygen by NIV (CPAP, BIPAP), high flow or non-rebreather mask, or
Need of mechanical ventilation/ECMO
- persistently increased respiratory rate, use of accessory muscles, inability to complete full sentences. Clinical judgement must be applied to determine whether a low oxygen saturation is indicative of disease progression or severity or is habitual for a given patient (i.e., with underlying chronic lung disease).
NIV=non-invasive ventilation. CPAP= Continuous Positive Airway Pressure, BPAP= Bi-level Positive Airway Pressure, ECMO = extracorporeal membrane oxygenation.
Additional inclusion criteria are given in the intervention-specific sub-protocols.
Note: these are based on the same criteria as in the WHO living guidelines recommending corticosteroid treatment for severe and critical COVID-195.
In addition, the following specific inclusion criteria apply:
SI-01. Immunocompromised patients defined as the presence of at least one of the following conditions9:
- Hematological malignancy or pre-malignancy, except acute leukemia or history of lymphoma
- Organ transplant recipients, except recipients of bone marrow or solid organ transplant last 6 months, or with transplant rejection last 6 months
- HIV positive with CD4 count < 350 cells and on stable antiretroviral therapy
- Primary immunodeficiency
- Rheumatoid arthritis, lupus, vasculitis, inflammatory bowel disease or other autoimmune disorder for which a patient is being treated with systemic immunosuppressive medication
- Other specified cause, such as history of cancer, cancer treatment or other condition that in the opinion of the investigator could cause impaired host immunity
SI-02. Elevation of 2 or more inflammatory markers above the following cutoffs:
- Ferritin > 700 ug/l
- LDH > 400 U/L
- CRP > 75 mg/L
Note: Carefully check exclusion criteria SE-01, SE-20 and SE-21 (immunosuppressive therapy), SE-22 (medical condition), SE-13 (neutropenia) and SE-14 (lymphopenia) for eligibility criteria.
Immunocompromised patients should receive appropriate SoC, including anti-SARS-CoV2 monoclonal antibodies or emerging antiviral treatment, if available and indicated by current treatment guidelines at time of inclusion.
EXCLUSION CRITERIA:
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.
• 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
Sites / Locations
- Medical University of Innsbruck (University Hospital for Neurosurgery)
- Medical Unversity of Innsbruck (Joint Institute for Emergency Medicine and Critical Care)
- Medical Unversity of Innsbruck (University Hospital for Anaesthesia and Intensive Care)
- Erasme Hospital
- UZ Brussel
- Cliniques Universitaires Saint-Luc
- St Anne University Hospital
- CHU Amiens Picardie (ICU)
- CHU Amiens Picardie (ID)
- CHU de Bordeaux / Hopital Pellegrin (ICU)
- CHU de Bordeaux / Hopital Pellegrin (ID)
- Louis Mourier (ID)
- Lous Mourier (ICU)
- CHU François Mitterrand
- CHU Lille - Hopital Roger Salengro -Pôle Rèanimaition
- Hopital de la Croix - Rousse - HCL (ICU)
- Hopital de la Croix - Rousse - HCL (ID)
- GHRMSA Hopital Emile Muller (ICU)
- GHRMSA Hopital Emile Muller (IM)
- Hôpital Saint-Antoine (ICU)
- Hôpital Saint-Antoine (ID)
- Hôpital Bichat - Claude Bernard (ICU)
- Hôpital Bichat - Claude Bernard (ID)
- Gesundheit Nord gGmbH (GeNo)
- Technische Universität München (TUM) - Klinikum rechts der Isar
- Evangelismos Hospital
- Attikon University Hospital
- University of Debrecen (Clinic for Infectology)
- University of Pécs
- University of Szeged (Pandemic Clinics)
- Cork University Hospital
- St Vincent's University Hospital
- Mater Misericordiae University Hospital
- St James's Hospital, Dublin
- Beaumont Hospital, Dublin
- Tallaght University Hospital
- University Hospital Galway
- University Hospital Limerick
- Ospedale Santa Maria Annunziata, Malattie Infettive
- ASST - Spedali Civili di Brescia - University of Brescia
- ATS Sardegna - PO SS Trinità, U.O.C. Malattie Infettive
- Azienda Opsedaliera Universitaria Mater Domini, U.O. Malattie Infettive e Tropicali
- ASL Frosinone - Ospedale Fabrizio Spaziani, U.O.C. Medicina Interna
- Ospedale S.M. Goretti di Latina, U.O.C. Malattie Infettive
- Ospedale Mater Salutis di Legnago, U.O.C. di Pneumologia
- Ospedale Mater Salutis di Legnago, U.O.S. di Malattie Infettive
- ASST Santi Paolo e Carlo, S.C. Malattie Infettive
- Azienda Ospedaliera Universitaria Vanvitelli, U.O.C. Malattie Infettive
- AOU Policlinico "P. Giaccone", U.O.C. Malattie Infettive
- Azienda Ospedaliera Ospedali Riuniti Marche Nord, U.O.C. Malattie Infettive
- ASL Taranto - Ospedale Oncologico San Giuseppe Moscati, U.O.C. Pneumologia
- AOU Città della Salute e Scienza Presidio Molinette
- Azienda Sanitaria Universitaria Giuliano Isontina (ASU GI), S.C. Malattie Infettive
- IRCCS Ospedale Sacro Cuore Don Calabria, U.O.S. Malattie Infettive e Tropicali
- Azienda Ospedaliera Universitaria Integrata di Verona, U.O.C. Malattie Infettive e Tropicali
- Centre Hospitalier de Luxembourg
- Drammen (Vestre Viken) Hospital
- Østfold sykehuset i Kalnes
- Akershus Universitetssykehus
- Lovisenberg Diaconal Hospital
- OUS Ullevål
- Bærum Hospital
- Stavanger University Hospital
- University Hospital North Norway
- St. Olavs Hospital
- Vestfold Hospital
- CHMT - Centro Hospitalar do Médio Tejo- Hospital de Abrantes
- CHUC - Centro Hospitalar e Universitário de Coimbra
- CHUA-Faro - Centro Hospitalar Universitário do Algarve
- CHLC-HCC - Hospital Curry Cabral, Centro Hospitalar Universitário Lisboa Central
- CHLN - Centro Hospitalar Universitário Lisboa Norte
- CHLO - Centro Hospitalar de Lisboa Ocidental - HEM and HSFX
- CHSJ - São João Hospital Center
- HBA - Hospital Beatriz Ângelo
- University Hospital Bratislava, Kramare
- University Hospital Martin
- Nsp Trebisov, Svet Zdravia a.s.
- Faculty Hospital Trencin
- University Hospital Trnava
- Hospital Universitario Reina Sofia
- Hospital Universitario de Jaen
- Hospital Universitario La Paz
- Hospital Costa del Sol
- Hospital Virgen de la Victoria
- Hospital Universitario Virgen Macarena
- Hospital Universitario Virgen del Rocio
- Hospital Universitario Virgen de Valme
- Hacettepe Üniversitesi Tıp Fakültesi, İnfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı (Site 1)
- Hacettepe Üniversitesi Tıp Fakültesi, İnfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı (Site 2)
- Ankara Üniversitesi Tıp Fakültesi, Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı
- İstanbul Üniversitesi İstanbul Tıp Fakültesi, Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı
- Dokuz Eylül Üniversitesi Tıp Fakültesi Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı
Arms of the Study
Arm 1
Arm 2
Experimental
Placebo Comparator
Active arm
Comparator
4mg Baricitinib up to 14 days + SoC
Matching placebo up to 14 days + SoC