EU SolidAct: An Adaptive Pandemic and Emerging Infection Platform Trial

Sponsor
Oslo University Hospital (Other)
Overall Status
Recruiting
CT.gov ID
NCT04891133
Collaborator
Institut National de la Santé Et de la Recherche Médicale, France (Other), Epidemiological and Clinical Research Information Network (Other)
1,900
99
2
53.9
19.2
0.4

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2/Phase 3

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

Study Type:
Interventional
Anticipated Enrollment :
1900 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Corresponding placebo tablets
Primary Purpose:
Treatment
Official Title:
European DisCoVeRy for Solidarity: An Adaptive Pandemic and Emerging Infection Platform Trial
Actual Study Start Date :
Jun 3, 2021
Anticipated Primary Completion Date :
Dec 1, 2022
Anticipated Study Completion Date :
Dec 1, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Active arm

4mg Baricitinib up to 14 days + SoC

Drug: Baricitinib
4 mg baricitinib (2 tablets of 2 mg) once daily
Other Names:
  • Olumiant
  • Placebo Comparator: Comparator

    Matching placebo up to 14 days + SoC

    Drug: Placebo
    4 mg placebo (2 tablets of 2 mg) once daily

    Outcome Measures

    Primary Outcome Measures

    1. Occurrence of death within 60 days (primary end point, EU SolidAct part B) [60 days]

      The primary outcome for phase 3 trials in EU SolidAct part B is occurrence of death within 60 days

    2. Occurrence of disease progression within 14 days (primary end point, EU SolidAct part A) [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)

    3. SpO2/FiO2-ratio at day 5 (primary end point, phase 2 trials) [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

    Secondary Outcome Measures

    1. Occurrence of disease progression within 28 days (shared secondary end point for part A and B) [28 days]

      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

    2. Time to sustained recovery (shared secondary end point for part A and B) [90 days]

      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

    3. Time to first hospital discharge (shared secondary end point for part A and B) [90 days]

      Time from randomization to first hospital discharge within 90 days

    4. Disease state at Day 15 and Day 29 (shared secondary end point for part A and B) [28 days]

      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

    5. Time from randomization to recovery (shared secondary end point for part A and B) [90 days]

      Time from randomization to recovery defined as no need for oxygen

    6. SpO2/FiO2-ratio at Day 3, 5 and 8 (shared secondary end point for part A and B) [8 days]

      Respiratory dysfunction assessed by SpO2/FiO2-ratio at Day 3, 5 and 8

    7. Viral clearance during hospitalization (shared secondary end point for part A and B) [Days 1, 3, 5, 8 and 15]

      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

    8. Occurrence of serious adverse events within 90 days (shared secondary end point for part A and B) [90 days]

      Occurrence of serious adverse events leading to study treatment discontinuation or death

    9. Patient related outcomes at day 90 (shared secondary end point for part A and B) [90 days]

      The Oslo COVID-19 QLQ-PW80 subscale scores at Day 90

    Other Outcome Measures

    1. Changes in C-reactive protein from baseline [Days 1, 3, 5, 8, 15 and 22]

      Analyzed in blood samples collected at Days 1, 3, 5, 8, 15 and 22 (± 1 day) if still hospitalized

    2. Changes in Ferritin from baseline [Days 1, 3, 5, 8, 15 and 22]

      Analyzed in blood samples collected at Days 1, 3, 5, 8, 15 and 22 (± 1 day) if still hospitalized

    3. Changes in Lactate dehydrogenase from baseline [Days 1, 3, 5, 8, 15 and 22]

      Analyzed in blood samples collected at Days 1, 3, 5, 8, 15 and 22 (± 1 day) if still hospitalized

    4. Changes in D-dimer from baseline [Days 1, 3, 5, 8, 15 and 22]

      Analyzed in blood samples collected at Days 1, 3, 5, 8, 15 and 22 (± 1 day) if still hospitalized

    5. Changes in procalcitonin from baseline [Days 1, 3, 5, 8, 15 and 22]

      Analyzed in blood samples collected at Days 1, 3, 5, 8, 15 and 22 (± 1 day) if still hospitalized

    6. Changes in neutrophils from baseline [Days 1, 3, 5, 8, 15 and 22]

      Analyzed in blood samples collected at Days 1, 3, 5, 8, 15 and 22 (± 1 day) if still hospitalized

    7. Changes in lymphocytes from baseline [Days 1, 3, 5, 8, 15 and 22]

      Analyzed in blood samples collected at Days 1, 3, 5, 8, 15 and 22 (± 1 day) if still hospitalized

    8. Changes in White Blood Cell Count from baseline [Days 1, 3, 5, 8, 15 and 22]

      Analyzed in blood samples collected at Days 1, 3, 5, 8, 15 and 22 (± 1 day) if still hospitalized

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    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:

    1. SpO2<90% on room air, or

    2. SpO2 90-94% with a downwards trend and/or signs of respiratory distress*, or

    3. Need of oxygen by NIV (CPAP, BIPAP), high flow or non-rebreather mask, or

    4. 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.

    EU SOLIDACT PLATFORM 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Medical University of Innsbruck (University Hospital for Neurosurgery) Innsbruck Austria 6020
    2 Medical Unversity of Innsbruck (Joint Institute for Emergency Medicine and Critical Care) Innsbruck Austria 6020
    3 Medical Unversity of Innsbruck (University Hospital for Anaesthesia and Intensive Care) Innsbruck Austria 6020
    4 Erasme Hospital Brussels Belgium 1070
    5 UZ Brussel Brussels Belgium 1090
    6 Cliniques Universitaires Saint-Luc Brussels Belgium 1200
    7 CHU Saint-Pierre Brussel Belgium 1000
    8 St Anne University Hospital Brno Czechia 65691
    9 CHU Amiens Picardie (ICU) Amiens France 80054
    10 CHU Amiens Picardie (ID) Amiens France 80054
    11 CHU de Bordeaux / Hopital Pellegrin (ICU) Bordeaux France 33076
    12 CHU de Bordeaux / Hopital Pellegrin (ID) Bordeaux France 33076
    13 Louis Mourier (ID) Colombes France 92700
    14 Lous Mourier (ICU) Colombes France 92700
    15 CHU François Mitterrand Dijon France 21000
    16 CHU Lille - Hopital Roger Salengro -Pôle Rèanimaition Lille France 59037
    17 Hopital de la Croix - Rousse - HCL (ICU) Lyon France 69004
    18 Hopital de la Croix - Rousse - HCL (ID) Lyon France 69004
    19 GHRMSA Hopital Emile Muller (ICU) Mulhouse France 68100
    20 GHRMSA Hopital Emile Muller (IM) Mulhouse France 68100
    21 Hôpital Saint-Antoine (ICU) Paris France 75012
    22 Hôpital Saint-Antoine (ID) Paris France 75012
    23 Hôpital Bichat - Claude Bernard (ICU) Paris France 75017
    24 Hôpital Bichat - Claude Bernard (ID) Paris France 75017
    25 Gesundheit Nord gGmbH (GeNo) Bremen Germany 28177
    26 Justus-Leibig Universität (JLU) Geißen Germany 35392
    27 Medizinische Hochschule Hannover (MHH) Hannover Germany 30625
    28 Technische Universität München (TUM) - Klinikum rechts der Isar München Germany 81675
    29 Klinikum Saarbrücken gGmbH (SAAR) Saarbrücken Germany 66119
    30 Evangelismos Hospital Athens Greece 10675
    31 Attikon University Hospital Athens Greece 12462
    32 University of Debrecen (Clinic for Infectology) Debrecen Hungary 4031
    33 University of Pécs Pécs Hungary 7623
    34 University of Szeged (Pandemic Clinics) Szeged Hungary 6725
    35 Cork University Hospital Cork Ireland T12 DFK4
    36 St Vincent's University Hospital Dublin Ireland 4
    37 Mater Misericordiae University Hospital Dublin Ireland D07 R2WY
    38 St James's Hospital, Dublin Dublin Ireland D08 NHY1
    39 Beaumont Hospital, Dublin Dublin Ireland D09VZNO
    40 Tallaght University Hospital Dublin Ireland D24 NR0A
    41 University Hospital Galway Galway Ireland H91 YR71
    42 University Hospital Limerick Limerick Ireland V94 F858
    43 Ospedale Santa Maria Annunziata, Malattie Infettive Bagno A Ripoli Italy 50012
    44 ASST - Spedali Civili di Brescia - University of Brescia Brescia Italy 25123
    45 ATS Sardegna - PO SS Trinità, U.O.C. Malattie Infettive Cagliari Italy 09121
    46 Azienda Opsedaliera Universitaria Mater Domini, U.O. Malattie Infettive e Tropicali Catanzaro Italy 88100
    47 ASL Frosinone - Ospedale Fabrizio Spaziani, U.O.C. Medicina Interna Frosinone Italy 03100
    48 Ospedale S.M. Goretti di Latina, U.O.C. Malattie Infettive Latina Italy 04100
    49 Ospedale Mater Salutis di Legnago, U.O.C. di Pneumologia Legnano Italy 37045
    50 Ospedale Mater Salutis di Legnago, U.O.S. di Malattie Infettive Legnano Italy 37045
    51 Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, U.O.C. Malattie Infettive Milano Italy 20121
    52 ASST Santi Paolo e Carlo, S.C. Malattie Infettive Milano Italy 20142
    53 Azienda Ospedaliera Universitaria Vanvitelli, U.O.C. Malattie Infettive Napoli Italy 80138
    54 AOU Policlinico "P. Giaccone", U.O.C. Malattie Infettive Palermo Italy 90127
    55 Azienda Ospedaliera Ospedali Riuniti Marche Nord, U.O.C. Malattie Infettive Pesaro Italy 61122
    56 ASL Taranto - Ospedale Oncologico San Giuseppe Moscati, U.O.C. Pneumologia Taranto Italy 74010
    57 AOU Città della Salute e Scienza Presidio Molinette Torino Italy 10126
    58 Azienda Sanitaria Universitaria Giuliano Isontina (ASU GI), S.C. Malattie Infettive Trieste Italy 34128
    59 IRCCS Ospedale Sacro Cuore Don Calabria, U.O.S. Malattie Infettive e Tropicali Verona Italy 37024
    60 Azienda Ospedaliera Universitaria Integrata di Verona, U.O.C. Malattie Infettive e Tropicali Verona Italy 37314
    61 Centre Hospitalier de Luxembourg Luxembourg Luxembourg L-1210
    62 Haukeland University Hospital Bergen Norway 5021
    63 Drammen (Vestre Viken) Hospital Drammen Norway NO-3004
    64 Østfold sykehuset i Kalnes Grålum Norway 1714
    65 Akershus Universitetssykehus Lørenskog Norway 1478
    66 Lovisenberg Diaconal Hospital Oslo Norway 04400
    67 OUS Ullevål Oslo Norway N-0424
    68 Bærum Hospital Sandvika Norway 1346
    69 Stavanger University Hospital Stavanger Norway 4011
    70 University Hospital North Norway Tromsø Norway 9019
    71 St. Olavs Hospital Trondheim Norway 7006
    72 Vestfold Hospital Tønsberg Norway 3103
    73 CHMT - Centro Hospitalar do Médio Tejo- Hospital de Abrantes Abrantes Portugal 2200-202
    74 CHUC - Centro Hospitalar e Universitário de Coimbra Coimbra Portugal 3000-075
    75 CHUA-Faro - Centro Hospitalar Universitário do Algarve Faro Portugal
    76 CHLC-HCC - Hospital Curry Cabral, Centro Hospitalar Universitário Lisboa Central Lisboa Portugal 1050-099
    77 CHLN - Centro Hospitalar Universitário Lisboa Norte Lisboa Portugal 1649-035
    78 CHLO - Centro Hospitalar de Lisboa Ocidental - HEM and HSFX Lisbon Portugal 1349-019
    79 CHSJ - São João Hospital Center Lisbon Portugal 1349-019
    80 HBA - Hospital Beatriz Ângelo Loures Portugal 2674-514
    81 University Hospital Bratislava, Kramare Bratislava Slovakia 83105
    82 University Hospital Martin Martin Slovakia 036 01
    83 Nsp Trebisov, Svet Zdravia a.s. Trebišov Slovakia 075 01
    84 Faculty Hospital Trencin Trenčín Slovakia 91171
    85 University Hospital Trnava Trnava Slovakia 917 75
    86 Nemocnica AGEL Košice-Šaca a.s. Šaca Slovakia 14015
    87 Hospital Universitario Reina Sofia Córdoba Spain 14004
    88 Hospital Universitario de Jaen Jaén Spain 23001
    89 Hospital Universitario La Paz Madrid Spain 28046
    90 Hospital Costa del Sol Marbella Spain 29603
    91 Hospital Virgen de la Victoria Málaga Spain 29101
    92 Hospital Universitario Virgen Macarena Sevilla Spain 41009
    93 Hospital Universitario Virgen del Rocio Sevilla Spain 41013
    94 Hospital Universitario Virgen de Valme Sevilla Spain 41014
    95 Hacettepe Üniversitesi Tıp Fakültesi, İnfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı (Site 1) Ankara Turkey 06230
    96 Hacettepe Üniversitesi Tıp Fakültesi, İnfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı (Site 2) Ankara Turkey 06230
    97 Ankara Üniversitesi Tıp Fakültesi, Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı Ankara Turkey
    98 İstanbul Üniversitesi İstanbul Tıp Fakültesi, Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı Istanbul Turkey
    99 Dokuz Eylül Üniversitesi Tıp Fakültesi Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı İzmir Turkey 35340

    Sponsors and Collaborators

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

    Investigators

    • Study Chair: Domique Costagliola, PhD, Institut National de la Santé Et de la Recherche Médicale, France
    • Principal Investigator: Jose R Arribas, MD PhD, Hospital Universario La Paz, Madrid

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Marius Trøseid, Associated professor, MD, PhD, Oslo University Hospital
    ClinicalTrials.gov Identifier:
    NCT04891133
    Other Study ID Numbers:
    • EU SolidAct
    • 2021-000541-41
    First Posted:
    May 18, 2021
    Last Update Posted:
    Apr 22, 2022
    Last Verified:
    Apr 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    Yes
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Apr 22, 2022