EU SolidAct: An Adaptive Pandemic and Emerging Infection Platform Trial
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
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:
|
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
- 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
- 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)
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
EU SOLIDACT PLATFORM INCLUSION CRITERIA:
Participants are eligible to be included in the study only if all the following general inclusion (GI) criteria apply:
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GI1. ≥ 18 years of age
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GI2. Laboratory-confirmed SARS-CoV-2 infection (new infection or reinfection) as determined by PCR not more than 14 days old.
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GI3. Admitted to hospital
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GI4. Informed consent by the participant or legally authorized representative
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GI5A (SolidAct part A): Moderate disease state defined as hospitalised patients without oxygen therapy or oxygen by mask or nasal prongs needed, or
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GI5B (SolidAct part B): Severe/critical disease state defined as fulfilling at least one of the following criteria:
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SpO2<90% on room air, or
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SpO2 90-94% with a downwards trend and/or signs of respiratory distress*, or
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Need of oxygen by NIV (CPAP, BIPAP), high flow or non-rebreather mask, or
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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.- EU SolidAct
- 2021-000541-41