EU SolidAct: An Adaptive Pandemic and Emerging Infection Platform Trial

NCT04891133 | Terminated Phase 2 DMC FDA Drug

• 2 other identifiers: EU SolidAct2022-500385-99-00
• Study Type: interventional
• Target: 290
• Locations: 15 countries
• Sites: 92

Brief 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. 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.

Conditions

COVID-19; Emerging Infectious Disease

Outcome Measures

Primary Outcomes (3)

• 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

  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)

  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

  5 days

Secondary Outcomes (9)

• Occurrence of disease progression within 28 days (shared secondary end point for part A and B)

  28 days

• Time to sustained recovery (shared secondary end point for part A and B)

  90 days

• Time to first hospital discharge (shared secondary end point for part A and B)

  90 days

• Disease state at Day 15 and Day 29 (shared secondary end point for part A and B)

  28 days

• Time from randomization to recovery (shared secondary end point for part A and B)

  90 days

Other Outcomes (8)

• Changes in C-reactive protein from baseline

  Days 1, 3, 5, 8, 15 and 22

• Changes in Ferritin from baseline

  Days 1, 3, 5, 8, 15 and 22

• Changes in Lactate dehydrogenase from baseline

  Days 1, 3, 5, 8, 15 and 22

Study Arms (2)

Active arm

EXPERIMENTAL

4mg Baricitinib up to 14 days + SoC

Drug: Baricitinib

Comparator

PLACEBO COMPARATOR

Matching placebo up to 14 days + SoC

Drug: Placebo

Interventions

Baricitinib DRUG

4 mg baricitinib (2 tablets of 2 mg) once daily

Also known as: Olumiant

Active arm

Placebo DRUG

4 mg placebo (2 tablets of 2 mg) once daily

Comparator

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Note: these are based on the same criteria as in the WHO living guidelines recommending corticosteroid treatment for severe and critical COVID-195.
• 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

You may not qualify if:

• GE1. Anticipated transfer to another non-trial hospital within 72 hours
• 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.
• 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®.

Sponsors & Collaborators

• Oslo University Hospital: lead
• Institut National de la Santé Et de la Recherche Médicale, France: collaborator
• Epidemiological and Clinical Research Information Network: collaborator

Study Sites (92)

Medical University of Innsbruck (University Hospital for Neurosurgery)

Innsbruck, 6020, Austria

Location

Medical Unversity of Innsbruck (Joint Institute for Emergency Medicine and Critical Care)

Innsbruck, 6020, Austria

Location

Medical Unversity of Innsbruck (University Hospital for Anaesthesia and Intensive Care)

Innsbruck, 6020, Austria

Location

Erasme Hospital

Brussels, 1070, Belgium

Location

UZ Brussel

Brussels, 1090, Belgium

Location

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

Location

St Anne University Hospital

Brno, 65691, Czechia

Location

CHU Amiens Picardie (ICU)

Amiens, 80054, France

Location

CHU Amiens Picardie (ID)

Amiens, 80054, France

Location

CHU de Bordeaux / Hopital Pellegrin (ICU)

Bordeaux, 33076, France

Location

CHU de Bordeaux / Hopital Pellegrin (ID)

Bordeaux, 33076, France

Location

Louis Mourier (ID)

Colombes, 92700, France

Location

Lous Mourier (ICU)

Colombes, 92700, France

Location

CHU François Mitterrand

Dijon, 21000, France

Location

CHU Lille - Hopital Roger Salengro -Pôle Rèanimaition

Lille, 59037, France

Location

Hopital de la Croix - Rousse - HCL (ICU)

Lyon, 69004, France

Location

Hopital de la Croix - Rousse - HCL (ID)

Lyon, 69004, France

Location

GHRMSA Hopital Emile Muller (ICU)

Mulhouse, 68100, France

Location

GHRMSA Hopital Emile Muller (IM)

Mulhouse, 68100, France

Location

Hôpital Saint-Antoine (ICU)

Paris, 75012, France

Location

Hôpital Saint-Antoine (ID)

Paris, 75012, France

Location

Hôpital Bichat - Claude Bernard (ICU)

Paris, 75017, France

Location

Hôpital Bichat - Claude Bernard (ID)

Paris, 75017, France

Location

Gesundheit Nord gGmbH (GeNo)

Bremen, 28177, Germany

Location

Technische Universität München (TUM) - Klinikum rechts der Isar

München, 81675, Germany

Location

Evangelismos Hospital

Athens, 10675, Greece

Location

Attikon University Hospital

Athens, 12462, Greece

Location

University of Debrecen (Clinic for Infectology)

Debrecen, 4031, Hungary

Location

University of Pécs

Pécs, 7623, Hungary

Location

University of Szeged (Pandemic Clinics)

Szeged, 6725, Hungary

Location

Cork University Hospital

Cork, T12 DFK4, Ireland

Location

St Vincent's University Hospital

Dublin, 4, Ireland

Location

Mater Misericordiae University Hospital

Dublin, D07 R2WY, Ireland

Location

St James's Hospital, Dublin

Dublin, D08 NHY1, Ireland

Location

Beaumont Hospital, Dublin

Dublin, D09VZNO, Ireland

Location

Tallaght University Hospital

Dublin, D24 NR0A, Ireland

Location

University Hospital Galway

Galway, H91 YR71, Ireland

Location

University Hospital Limerick

Limerick, V94 F858, Ireland

Location

Ospedale Santa Maria Annunziata, Malattie Infettive

Bagno a Ripoli, 50012, Italy

Location

ASST - Spedali Civili di Brescia - University of Brescia

Brescia, 25123, Italy

Location

ATS Sardegna - PO SS Trinità, U.O.C. Malattie Infettive

Cagliari, 09121, Italy

Location

Azienda Opsedaliera Universitaria Mater Domini, U.O. Malattie Infettive e Tropicali

Catanzaro, 88100, Italy

Location

ASL Frosinone - Ospedale Fabrizio Spaziani, U.O.C. Medicina Interna

Frosinone, 03100, Italy

Location

Ospedale S.M. Goretti di Latina, U.O.C. Malattie Infettive

Latina, 04100, Italy

Location

Ospedale Mater Salutis di Legnago, U.O.C. di Pneumologia

Legnano, 37045, Italy

Location

Ospedale Mater Salutis di Legnago, U.O.S. di Malattie Infettive

Legnano, 37045, Italy

Location

ASST Santi Paolo e Carlo, S.C. Malattie Infettive

Milan, 20142, Italy

Location

Azienda Ospedaliera Universitaria Vanvitelli, U.O.C. Malattie Infettive

Napoli, 80138, Italy

Location

AOU Policlinico "P. Giaccone", U.O.C. Malattie Infettive

Palermo, 90127, Italy

Location

Azienda Ospedaliera Ospedali Riuniti Marche Nord, U.O.C. Malattie Infettive

Pesaro, 61122, Italy

Location

ASL Taranto - Ospedale Oncologico San Giuseppe Moscati, U.O.C. Pneumologia

Taranto, 74010, Italy

Location

AOU Città della Salute e Scienza Presidio Molinette

Torino, 10126, Italy

Location

Azienda Sanitaria Universitaria Giuliano Isontina (ASU GI), S.C. Malattie Infettive

Trieste, 34128, Italy

Location

IRCCS Ospedale Sacro Cuore Don Calabria, U.O.S. Malattie Infettive e Tropicali

Verona, 37024, Italy

Location

Azienda Ospedaliera Universitaria Integrata di Verona, U.O.C. Malattie Infettive e Tropicali

Verona, 37314, Italy

Location

Centre Hospitalier de Luxembourg

Luxembourg, L-1210, Luxembourg

Location

Drammen (Vestre Viken) Hospital

Drammen, NO-3004, Norway

Location

Østfold sykehuset i Kalnes

Grålum, 1714, Norway

Location

Akershus Universitetssykehus

Lørenskog, 1478, Norway

Location

Lovisenberg Diaconal Hospital

Oslo, 04400, Norway

Location

OUS Ullevål

Oslo, N-0424, Norway

Location

Bærum Hospital

Sandvika, 1346, Norway

Location

Stavanger University Hospital

Stavanger, 4011, Norway

Location

University Hospital North Norway

Tromsø, 9019, Norway

Location

St. Olavs Hospital

Trondheim, 7006, Norway

Location

Vestfold Hospital

Tønsberg, 3103, Norway

Location

CHMT - Centro Hospitalar do Médio Tejo- Hospital de Abrantes

Abrantes, 2200-202, Portugal

Location

CHUC - Centro Hospitalar e Universitário de Coimbra

Coimbra, 3000-075, Portugal

Location

CHUA-Faro - Centro Hospitalar Universitário do Algarve

Faro, Portugal

Location

CHLC-HCC - Hospital Curry Cabral, Centro Hospitalar Universitário Lisboa Central

Lisbon, 1050-099, Portugal

Location

CHLO - Centro Hospitalar de Lisboa Ocidental - HEM and HSFX

Lisbon, 1349-019, Portugal

Location

CHSJ - São João Hospital Center

Lisbon, 1349-019, Portugal

Location

CHLN - Centro Hospitalar Universitário Lisboa Norte

Lisbon, 1649-035, Portugal

Location

HBA - Hospital Beatriz Ângelo

Loures, 2674-514, Portugal

Location

University Hospital Bratislava, Kramare

Bratislava, 83105, Slovakia

Location

University Hospital Martin

Martin, 036 01, Slovakia

Location

Nsp Trebisov, Svet Zdravia a.s.

Trebišov, 075 01, Slovakia

Location

Faculty Hospital Trencin

Trenčín, 91171, Slovakia

Location

University Hospital Trnava

Trnava, 917 75, Slovakia

Location

Hospital Universitario Reina Sofia

Córdoba, 14004, Spain

Location

Hospital Universitario de Jaen

Jaén, 23001, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Costa del Sol

Marbella, 29603, Spain

Location

Hospital Virgen de la Victoria

Málaga, 29101, Spain

Location

Hospital Universitario Virgen Macarena

Seville, 41009, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Hospital Universitario Virgen de Valme

Seville, 41014, Spain

Location

Hacettepe Üniversitesi Tıp Fakültesi, İnfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı (Site 1)

Ankara, 06230, Turkey (Türkiye)

Location

Hacettepe Üniversitesi Tıp Fakültesi, İnfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı (Site 2)

Ankara, 06230, Turkey (Türkiye)

Location

Ankara Üniversitesi Tıp Fakültesi, Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı

Ankara, Turkey (Türkiye)

Location

İstanbul Üniversitesi İstanbul Tıp Fakültesi, Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı

Istanbul, Turkey (Türkiye)

Location

Dokuz Eylül Üniversitesi Tıp Fakültesi Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı

Izmir, 35340, Turkey (Türkiye)

Location

Related Publications (2)

• 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.

  PMID: 36627655 RESULT

• Kreuzberger 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.

  PMID: 34473343 DERIVED

MeSH Terms

Conditions

COVID-19; Communicable Diseases, Emerging

Interventions

baricitinib

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Communicable Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Domique Costagliola, PhD

  Institut National de la Santé Et de la Recherche Médicale, France

  STUDY CHAIR

• Jose R Arribas, MD PhD

  Hospital Universario La Paz, Madrid

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Corresponding placebo tablets
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associated professor, MD, PhD

Study Record Dates

• First Submitted: May 7, 2021
• First Posted: May 18, 2021
• Study Start: June 3, 2021
• Primary Completion: December 15, 2022
• Study Completion: January 23, 2023
• Last Updated: February 6, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE

Locations

IE (8); GR (2); IT (17); LU (1); SL (5); BE (3); AU (3); ES (8); NO (10); DE (2); TU (5); FR (16); PT (8); CZ (1); HU (3)