Randomised Evaluation of COVID-19 Therapy (RECOVERY) in Children With PIMS-TS in Switzerland (SWISSPED-RECOVERY)
Phase: PHASE3
Conditions: Paediatric Inflammatory Multisystem Syndrome-Temporally Associated With SARS-CoV-2 (PIMS-TS)
Sponsor: University Children's Hospital Basel

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Randomised Evaluation of COVID-19 Therapy (RECOVERY) 
Amendment (18.01.2022, V1.3) to Amendment (16.06.2021 V1.2)  
Summary 
This is an amendment to the amendment (Version 1.2, 16.06.2021) to the addendum 
(Version 1.1, 23.03.2021) to the RECOVERY international protocol (Version 13.0, 26-01-
2021) providing further information relevant to the implementation of the study at Swiss study 
sites. The following aspects are covered: 
1. Study synopsis 
2. Study administrative structure in Switzerland 
3. Ethical and Regulatory aspects 
4. Study population 
5. Relevant randomisations 
6. Screening and enrolment  
7. Local substudies 
8. Data collection 
9. Regulatory aspects and safety 
10. Quality control and data protection 
11. Monitoring 
12. Funding 
The RECOVER UK Paediatric Trial Management Group has reviewed and approved these 
aspects.  
Study Type: Adaptive platform trial (Sister trial to the paediatric arms in RECOVERY UK) 
Study Categorisation: A 
Study Identifier: SWISSPED-RECOVERY 
 
Sponsor-investigator: 
Name: Dr. Julia Bielicki, MD MPH PhD 
Paediatric Infectious Diseases and Vaccinology 
Universität-Kinderspital beider Basel (UKBB) 
Spitalstrasse 33, 4056 Basel, CH 
Phone + 41 61 7041212, Fax +41 61 704 12 13 
Email: julia.bielicki@ukbb.ch 
 
_______________________________ _ 
        _______________________________ 
Place/Date                                                                 Signature 
 
Co-Chief Investigator (Switzerland): 
Name: Prof. Luregn Schlapbach 
 
 
_______________________________ _ 
        _______________________________ 
Place/Date                                                                 Signature 

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Signature Pages 
Study Title 
 
Randomised Evaluation of COVID-19 Therapy (RECOVERY) 
 
The Sponsor-Investigator, Co-Chief Investigator and Trial Statistician have approved the 
International Protocol Version 13.0, 26-01-2021 and the Amendment (Version 1.3, dated 18. 
January 2022) , and confirm hereby to conduct the study according to the protocol, current 
version of the World Medical Association Declaration of Helsinki, ICH-GCP guidelines or ISO 
14155 norm if applicable and the local legally applicable requirements. 
 
Sponsor-Investigator: 
Dr. Julia Bielicki, MD MPH PhD 
 
 
_______________________________ _ 
        _______________________________ 
Place/Date                                                                 Signature 
 
Co-Chief Investigator: 
Prof. Luregn Schlapbach 
 
_______________________________ _ 
        _______________________________ 
Place/Date                                                                 Signature 
 
 
Statistician: 
Andrew Atkinson, PhD 
 
 
_______________________________ _ 
        _______________________________ 
Place/Date                                                                 Signature 
 
 
 
 
 

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Local Principal Investigator at study site: 
I have read and understood this trial protocol and agree to conduct the trial as set out in this 
study protocol, the current version of the World Medical Association Declaration of Helsinki, 
ICH-GCP guidelines or ISO 14155 norm and the local legally applicable requirements. 
 
Site 
 
 
 
University of Basel Children’s Hospital 
 
 
 
 
Spitalstrasse 33 
 
 
 
 
4056 Basel 
Principal investigator  
PD Dr. med. Maya André 
 
 
_______________________________ _ 
        _______________________________ 
Place/Date                                                                 Signature 
 
 

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Local Principal Investigator at study site: 
I have read and understood this trial protocol and agree to conduct the trial as set out in this 
study protocol, the current version of the World Medical Association Declaration of Helsinki, 
ICH-GCP guidelines or ISO 14155 norm and the local legally applicable requirements. 
 
Site 
 
 
 
University Children`s Hospital Zuerich 
 
 
 
 
Steinwiesstr. 75 
 
 
 
 
8032 Zuerich 
Principal investigator  
PD Dr. med. PhD Johannes Trueck 
 
 
_______________________________ _ 
        _______________________________ 
Place/Date                                                                 Signature 
 
 
 
 

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Local Principal Investigator at study site: 
I have read and understood this trial protocol and agree to conduct the trial as set out in this 
study protocol, the current version of the World Medical Association Declaration of Helsinki, 
ICH-GCP guidelines or ISO 14155 norm and the local legally applicable requirements. 
 
 
Site 
 
 
 
Department of Pediatrics, University of Bern 
 
 
 
 
Inselspital 
 
 
 
 
3010 Bern 
Principal investigator  
Dr. med. Nina Schoebi 
 
 
 
 
_______________________________ _ 
        _______________________________ 
Place/Date                                                                 Signature 
 
 

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Local Principal Investigator at study site: 
I have read and understood this trial protocol and agree to conduct the trial as set out in this 
study protocol, the current version of the World Medical Association Declaration of Helsinki, 
ICH-GCP guidelines or ISO 14155 norm and the local legally applicable requirements. 
 
 
Site 
 
 
 
Children’s Hospital of Eastern Switzerland, St. Gallen 
 
 
 
 
Claudiusstrasse 6 
 
 
 
 
9006 St. Gallen 
 
 
 
 
+41 71 243 13 77 
Principal investigator  
Dr. med. univ. Douggl G N Bailey 
 
 
 
_______________________________ _ 
        _______________________________ 
Place/Date                                                                 Signature 
 
 

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Local Principal Investigator at study site: 
I have read and understood this trial protocol and agree to conduct the trial as set out in this 
study protocol, the current version of the World Medical Association Declaration of Helsinki, 
ICH-GCP guidelines or ISO 14155 norm and the local legally applicable requirements. 
 
 
Site 
 
 
 
Department of Pediatrics, Cantonal Hospital Fribourg 
 
 
 
 
Chemin des Pensionnats 2-6 
 
 
 
 
1752 Villars-sur-Glâne 
 
 
 
 
0041 260 306 3542 
Principal investigator  
Dr. med. Petra Zimmermann 
 
 
 
 
 
_______________________________ _ 
        _______________________________ 
Place/Date                                                                 Signature 
 
 

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Local Principal Investigator at study site: 
I have read and understood this trial protocol and agree to conduct the trial as set out in this 
study protocol, the current version of the World Medical Association Declaration of Helsinki, 
ICH-GCP guidelines or ISO 14155 norm and the local legally applicable requirements. 
 
 
Site 
 
 
 
Department of Pediatrics, Cantonal Hospital Luzern 
 
 
 
 
Spitalstrasse 
 
 
 
 
Postfach 
 
 
 
 
6000 Luzern 16 
Principal investigator  
Dr. med. Michael Buettcher 
 
 
 
 
 
 
 
 
_______________________________ _ 
        _______________________________ 
Place/Date                                                                 Signature 
 
 

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Local Principal Investigator at study site: 
I have read and understood this trial protocol and agree to conduct the trial as set out in this 
study protocol, the current version of the World Medical Association Declaration of Helsinki, 
ICH-GCP guidelines or ISO 14155 norm and the local legally applicable requirements. 
 
 
Site 
 
 
 
Pediatric Intensive Care Unit 
Department of Pediatrics,  
University Hospital of Lausanne (CHUV) 
Lausanne, Switzerland 
+41 79 556 40 82 
Principal investigator  
Dr. Marie-Helene Perez 
 
 
 
 
 
_______________________________ _ 
        _______________________________ 
Place/Date                                                                 Signature 
 
 
 

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Local Principal Investigator at study site: 
I have read and understood this trial protocol and agree to conduct the trial as set out in this 
study protocol, the current version of the World Medical Association Declaration of Helsinki, 
ICH-GCP guidelines or ISO 14155 norm and the local legally applicable requirements. 
 
Site 
 
 
 
Division of Neonatal and Pediatric Intensive Care, 
 Department of Child, Woman and, Adolescent Medecine,  
Geneva University Hospitals and Faculty of Medicine,  
Geneva, Switzerland 
+41 79 55 34 486 
Principal investigator  
Dr. med. Serge Grazioli  
 
 
 
 
 
_______________________________ _ 
        _______________________________ 
Place/Date                                                                 Signature 

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Local Principal Investigator at study site: 
I have read and understood this trial protocol and agree to conduct the trial as set out in this 
study protocol, the current version of the World Medical Association Declaration of Helsinki, 
ICH-GCP guidelines or ISO 14155 norm and the local legally applicable requirements. 
 
 
Site 
 
 
 
Cantonal hospital Aarau 
Department of paediatrics 
Tellstrasse 25 
5001 Aarau 
 
 
 
 
 
Principal investigator   
Prof. Dr. med. Henrik Köhler 
 
 
 
 
_______________________________ _ 
        _______________________________ 
Place/Date                                                                 Signature 
 
 
 
 

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Local Principal Investigator at study site: 
I have read and understood this trial protocol and agree to conduct the trial as set out in this 
study protocol, the current version of the World Medical Association Declaration of Helsinki, 
ICH-GCP guidelines or ISO 14155 norm and the local legally applicable requirements. 
 
 
Site 
 
 
 
Ente Ospedaliero Cantonale Ticino (EOC) 
Pediatrica 
  
 
 
 
6500 Bellinzona 
 
 
 
 
Principal investigator   
Dr. med. Federica Vanoni 
 
 
 
 
 
 
_______________________________ _ 
        _______________________________ 
Place/Date                                                                 Signature 
 
 
 

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1. Study synopsis 
Sponsor / Sponsor-
Investigator 
Dr. Julia Bielicki, MD MPH PhD 
Paediatric Infectious Diseases and Vaccinology 
Universität-Kinderspital beider Basel (UKBB) 
Study Title: 
Swiss Pediatric Randomised Evaluation of COVID-19 Therapy 
Short Title / Study 
ID: 
SWISSPED-RECOVERY  
Protocol Version 
and Date: 
International Protocol Version 13.0, 26-01-2021 
Swiss Addendum V1.1, 23 March 2021  
Amendment to the Swiss Addendum V1.3, 18. January 2022 
Trial registration: 
 NCT04826588 
Study category and 
Rationale 
A, since pharmacological products will be used according to their 
SmPCs in an open-label design (kofam categorizer 11.02.2021).  
Clinical Phase: 
The randomization described in that part is risk category A 
The original Recovery Protocol is a Complex clinical trial (phase III-
IV) 
Background and 
Rationale: 
In 2019 a novel coronavirus-disease (COVID-19) emerged in 
Wuhan, China. A month later the Chinese Center for Disease 
Control and Prevention identified a new beta-coronavirus (SARS 
coronavirus 2, or SARS-CoV-2) as the aetiological agent. The 
clinical manifestations of COVID-19 range from asymptomatic 
infection or mild, transient symptoms to severe viral pneumonia with 
respiratory failure. In May 2020 a new COVID-associated 
inflammatory syndrome in children was identified, Paediatric 
Inflammatory Multisystem Syndrome - Temporally associated with 
SARS-CoV-2 (PIMS-TS).5 A rapid international consensus process 
identified the need to evaluate corticosteroids and intravenous 
immunoglobulin (IVIg) as initial therapies in PIMS-TS, and 
confirmed tocilizumab and anakinra as biological anti-inflammatory 
agents to be evaluated as a second line therapy. 
Objective(s): 
The primary objective is to compare the effect of study treatments 
on the duration of hospital stay after randomization. 
The secondary objectives are to assess the effects of study 
treatments on all-cause mortality at 28 days; and, among patients 
not on invasive mechanical ventilation at baseline, the composite 
endpoint of death or need for invasive mechanical ventilation or 
ECMO. 
Other objectives include the assessment of the effects of study 
treatments on the need for any ventilation (and duration of invasive 
mechanical ventilation), renal replacement therapy and thrombotic 
events and cardiac, neurological long-term outcome and quality of 
life post-infection as well as vaccine coverage. 

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Outcome(s): 
Primary outcome: Duration of hospital stay after randomisation. 
Secondary 
outcomes: 
all-cause 
mortality 
28 
days 
after 
randomization, hospitalization status, use of ventilation including 
days of use and type and use of renal dialysis or hemofiltration at 
28 days after randomization. Echocardiography and quality of life 6 
months after randomization 
Study design: 
Swissped-Recovery is a sister trial to RECOVERY. The protocol 
describes an overarching trial design to provide reliable evidence 
on the efficacy of candidate therapies for children hospitalised with 
PIMS-TS. It is an adaptive pragmatic platform trial with an open-
label randomisation as described below. New trial arms can be 
added as evidence emerges that other candidate therapeutics 
should be evaluated. 
The protocol is deliberately flexible so that it is suitable for a wide 
range of settings, allowing: 
- 
a broad range of patients to be enrolled in large numbers; 
- 
randomisation between only those treatment arms that are 
both available at the hospital and not believed by the 
enrolling doctor to be contraindicated (e.g. by particular co-
morbid conditions or concomitant medications); 
- 
treatment arms to be added or removed according to the 
emerging evidence; and 
- 
additional substudies may be added to provide more 
detailed information on side effects or sub-categorisation of 
patient types but these are not the primary objective and are 
not required for participation. 
Inclusion / 
Exclusion criteria: 
Patients are eligible for the study if all of the following are true:  
(i) Hospitalised children (aged <18 years old) 
(ii) SARS-CoV-2 infection associated disease (clinically suspected 
or laboratory confirmed) with evidence of single or multi-organ 
dysfunction (called Paediatric Multisystem Inflammatory Syndrome 
temporally associated with COVID-19 [PIMS-TS]).  
(iii) No medical history that might, in the opinion of the attending 
clinician, put the patient at significant risk if he/she were to 
participate in the trial  
Neonates/infants with a corrected gestational age of <= 44 weeks 
will be excluded.  
In addition, if the attending clinician believes that there is a specific 
contra-indication to one of the active drug treatment arms or that 
the patient should definitely be receiving one of the active drugs, 
patient will not be available for randomisation. 

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Measurements and 
procedures: 
 
All eligible patients are randomly allocated to two treatment arms in 
the participating hospital: Methylprednisolone 10mg/kg intravenous 
for three days vs intravenous immunoglobulin (main randomisation 
part A). The UK study allows a subsequent randomisation for 
children with PIMS-TS not covered by the current Swiss 
addendum (hyper-inflammatory state associated with COVID-19). 
For patients for whom not all the trial arms are appropriate or at 
locations where not all are available, randomisation will be between 
fewer arms. 
To facilitate participation, patient enrolment and all other trial 
procedures are greatly streamlined. Informed consent is simple and 
data entry is minimal. Follow-up information is recorded at a single 
timepoint and may be ascertained by contacting participants in 
person, by phone or electronically, or by review of medical records 
and databases. 
At randomisation, information will be collected on the identity of the 
randomising clinician and of the patient, age, sex, major co-
morbidity, pregnancy, COVID-19 onset date and severity, and any 
contraindications to the study treatments. The main outcomes will 
be death (with date and probable cause), discharge (with date), 
need for ventilation (with number of days recorded) and need for 
renal replacement therapy. Reminders will be sent if outcome data 
have not been recorded by 28 days after randomisation. 
Study Interventions:  Patients will be randomized 1:1 to the following treatments:  
- 
Methylprednisolone 10 mg/kg intravenously once daily for 3 
days (max 1 g per dose) 
- 
Human normal immunoglobulin (IVIg) 2g/kg intravenously 
as a single dose in line with guidance for dosing and 
administration in Kawasaki disease 
The second stage randomisation specified in the International 
Protocol is not be available in the Amendment (V1.3, 18. January 
2022) of the Swissped-Recovery Addendum V1.1, 23 March 2021. 
Number of 
Participants with 
Rationale: 
The larger the number randomised the more accurate the results 
will be, but the numbers that can be randomised will depend 
critically on the epidemic progress and the influence of vaccination.  
For the period of the trial, we estimate that between approximately 
50 and 120 children across the 10 centres can be recruited. 
According to expert opinion, the best estimate (i.e. the mode) would 
be approximately 80 children assigned to each of the arms using 
1:1randomisation (i.e. 40 in each arm). Accordingly, for the primary 
endpoint comparing mean log transformed length of stay for those 
on Methylprednisolone 10 mg/kg for three days (N=40) to those on 
Immunoglobulins  (N=40) using a two-sided t-test and with a 5% 
significance level, we would be able to detect a normalized effect 
size of approximately 0.65 with 80% power. 

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Study Duration: 
 
 
 
 
The desirable start date for screening is April  2021. Because of the 
adaptive nature of the trial and the expected epidemiology and key 
therapeutic questions for PIMS-TS in Switzerland, there is currently 
no pre-defined stop date for the trial. We expect an initial trial 
duration of 21 months.  
Study Schedule: 
 
April 2021 FPFV 
December 2022 LPLV 
Study Centre(s): 
Multi-centre study across ten Swiss centres as represented above.  
Statistical 
Considerations: 
 
For all outcomes, comparisons will be made between all 
participants randomised to the different treatment arms, 
 irrespective of whether they received their allocated treatment 
(“intention-to-treat” analyses). 
For the primary endpoint, the log transformed time to discharge (or 
death) will be compared between those on methylprednisolone 
10mg/kg intravenous or intravenous immunoglobulins. For time-to-
event analyses, the  treatment groups will be compared using the 
log-rank test. Kaplan-Meier estimates for the time to event will also 
be plotted (with associated log-rank p-values). For binary outcomes 
where the timing is unknown, the risk ratio and absolute risk 
difference will be calculated with confidence intervals and p-value 
reported. For the time to event endpoints discharge alive before 28 
days will assume safety from the event (unless there is additional 
data confirming otherwise). 
Allowance for multiple treatment comparisons will be made. A p-
value of less than 0.05 will be considered statistically significant 
throughout. 
GCP Statement: 
This study will be conducted in compliance with the protocol, the 
current version of the Declaration of Helsinki, the ICH-GCP or ISO 
EN 14155 (as far as applicable) as well as all national legal and 
regulatory requirements.  
 
 
2. Study administrative structure in Switzerland 
2.1 Sponsor-Investigator and Co-Chief Investigator 
 
Dr. Julia Bielicki, MD MPH PhD 
Paediatric Infectious Diseases and Vaccinology 
Universität-Kinderspital beider Basel (UKBB) 
Spitalstrasse 33, 4056 Basel, CH 
Phone + 41 61 7041212, Fax +41 61 704 12 13 
 
Prof. Luregn Schlapbach, MD, PhD 
Pediatric and Neonatal Intensive Care Unit 
University Children's Hospital Zurich – Eleonore Foundation 
Steinwiesstrasse 75 
CH-8032 Zurich  

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phone +41 44 266 37 90 
 
2.2 Principal Investigators 
• 
University Children`s Hospital Zurich (Kispi ZH): PD Dr. Johannes Trueck,  
• 
University of Basel Children`s Hospital (UKBB): Dr. Maya André 
• 
Department of Pediatrics, Inselspital Bern: Dr. Nina Schoebi,  
• 
Department of Pediatrics, University Hospital Geneva (HUG): Dr. Serge Grazioli 
• 
Department of Pediatrics, Centre Hospitalier Universitaire Vaudois (CHUV): PD Dr. Marie-
Helene Perez 
• 
Children`s Hospital of Eastern Switzerland: Dr Douggl Bailey 
• 
Kantonsspital Luzern: Dr. Michael Buettcher 
• 
Kantonsspital Fribourg: Dr. Petra Zimmermann 
• 
Kantonsspital Aarau: Prof. Dr. Henrik Koehler 
• 
Ente Ospedaliero Cantonale Ticino (EOC), pediatrica: Dr. Federica Vanoni  
 
2.3 Statistician 
Andrew Atkinson, PhD 
Paediatric Research Centre/SwissPedNet Hub Basel 
Universität-Kinderspital beider Basel (UKBB) 
Spitalstrasse 33, 4056 Basel, CH 
Phone + 41 61 7041212, Fax +41 61 704 12 13 
 
2.4 Monitoring Institution 
Paediatric Research Centre, UKBB, Spitalstrasse 33, 4056 Basel, CH 
Monitoring will be performed according to a monitoring schedule and will strictly involve staff 
outside of the trial. 
 
2.5 Independent Data Monitoring Committee 
The responsibility of the Independent Data Monitoring Committee (IDMC) will be to safeguard 
the interests of trial participants, assess the safety of the interventions during the trial, and 
contribute to monitoring the overall conduct of the clinical trial. The IDMC is independent of, 
but reports to, the TSG. The specific roles of the IDMC are to monitor evidence for treatment 
harm (e.g. toxicity data, SAEs, deaths), suggest additional data analyses (using blinded data 
where possible), for example, of main outcome measures, recommend whether the trial should 
continue to recruit participants or whether recruitment should be stopped due to safety 
reasons. A statistician or a named independent delegate will produce the report to the IDMC 
and will participate in IDMC meetings. Further details of IDMC functioning and procedures will 
be specified in the IDMC Charter agreed and signed by all IDMC members.  
 
2.6 Any other relevant Committee, Person, Organisation, Institution 
A Trial Steering Group will be formed comprising sponsor-investigator, other lead investigators 
(local and international, clinical and non-clinical), the trial manager and members of the 
Paediatric Research Centre at UKBB. The TSG will be responsible for the day-to-day running 
and management of the trial. Full details of the TSG functioning, including the frequency of 
meeting and a list of TSG members will be detailed in the TSG Charter. 
To effectively interact with the RECOVERY UK study, the Swiss TSG will co-opt an expert from 
the RECOVERY trial group (Prof. Saul Faust, proxy Prof. Elizabeth Whittaker) who will be 

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invited to the regular TSG meetings and cc`d on relevant TSG conversations. In reverse, a 
delegate from the Swiss TSG is being invited to the regular RECOVERY meetings. 
Swiss PedNet (https://www.swisspednet.ch/) will provide infrastructure support for study 
coordination, GCP, and monitoring. 
 
3. Ethical and Regulatory aspects 
Prior to study conduct, protocol, proposed patient information, consent form and other study-
specific documents will be submitted to the Ethikkommission Nordwest- und Zentralschweiz 
(EKNZ) (Ethics Committee Northwest/Central Switzerland), other relevant ethics committees 
in Switzerland. Any amendment to the protocol will be approved by these institutions. 
The decision of the CEC concerning the conduct of the study will be made in writing to the 
Sponsor-Investigator before commencement of this study. The clinical study can only begin 
once approval from all required authorities has been received. 
 
3.1 Study registration 
This study is registered on the Swiss National Clinical Trials Portal and ClinicalTrial.gov (NCT 
04826588). Registration will be updated if amendments are approved.  
 
3.2 Categorisation of the study 
The study category is class A, since pharmacological products will be used according to their 
SmPCs in an open-label design (kofam categorizer 11.02.2021). 
 
3.3 Competent Ethics Committee (CEC) 
The responsible investigator at each site ensures that approval from an appropriately 
constituted CEC is obtained for SWISSPED-RECOVERY. 
Reporting duties and allowed time frame (all changes in the research activity and all 
unanticipated problems involving risks to humans, including in case of planned or premature 
study end and the final report) and changes made to the protocol will not be made without prior 
Sponsor and CEC approval, except where necessary to eliminate apparent immediate hazards 
to study participants. 
Premature study end, premature treatment arm end or interruption of the study will be reported 
within 15 days. The regular end of the study will be reported to the CEC within 90 days, the 
final study report will be submitted within one year after study end. Amendments are reported 
according to section 2.10. 
 
3.4 Swissmedic 
Not applicable. 
 
3.5 Ethical Conduct of the Study 
The study will be carried out in accordance to the protocol and with principles enunciated in 
the current version of the Declaration of Helsinki, the guidelines of Good Clinical Practice 
(GCP) issued by ICH, in case of medical device: the European Regulation on medical devices 
2017/745 and the ISO Norm 14155 and ISO 14971, the Swiss Law and Swiss regulatory 
authority’s requirements. The CEC and regulatory authorities will receive annual safety and 
interim reports and be informed about study stop/end in agreement with local requirements. 
Study setup, randomization schedule, study conduct, and data capture will be aligned and 
harmonized with the UK RECOVERY trial to ensure comparability of data and enabling pre-
planned later meta-analyses of patient-level data. For this purpose, a data sharing agreement 
between the Swiss study and RECOVERY will be signed. 

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3.6 Declaration of interest 
There are no potential conflicts of interest to disclose. 
 
3.7 Patient information and Informed Consent 
For details please refer to section 7.4 and 7.5 
 
3.8 Participant privacy and confidentiality 
The investigator affirms and upholds the principle of the participant's right to privacy and that 
they shall comply with applicable privacy laws. Especially, anonymity of the participants shall 
be guaranteed when presenting the data at scientific meetings or publishing them in scientific 
journals.  
Individual subject medical information obtained as a result of this study is considered 
confidential and disclosure to third parties is prohibited. Subject confidentiality will be further 
ensured by utilising subject identification code numbers to correspond to treatment data in the 
computer files. 
For data verification purposes, authorized representatives of the Sponsor-Investigator, a 
competent authority (e.g. Swissmedic), or an ethics committee may require direct access to 
parts of the medical records relevant to the study, including participants’ medical history. 
 
3.9 Early termination of the study 
The Sponsor-Investigator may terminate the study prematurely according to certain 
circumstances, for example: 
• 
ethical concerns, 
• 
when the safety of the participants is doubtful or at risk, respectively, 
• 
alterations in accepted clinical practice that make the continuation of a clinical trial 
unwise,  
• 
early evidence of benefit or harm of the experimental intervention. 
 
3.10 
Protocol amendments 
Substantial amendments are only implemented after approval of the CEC and CA respectively. 
Amendments affecting the International and national Protocol will be immediately notified to 
the CEC and CA and implemented as soon as approval has been obtained to ensure alignment 
with the main RECOVERY/Swissped-Recovery trial.  
Under emergency circumstances, deviations from the protocol to protect the rights, safety and 
well-being of human subjects may proceed without prior approval of the sponsor and the 
CEC/CA. Such deviations shall be documented and reported to the sponsor and the CEC/CA 
as soon as possible. 
All non-substantial amendments are communicated to the CA as soon as possible if applicable 
and to the CEC within the Annual Safety Report (ASR). 
 
4. Study objectives 
4.1 Primary objective  
The primary objective is to provide reliable estimates of the effect of study treatment on  
hospital length of stay through to 28 days after randomisation. 
 
4.2 Secondary objective 
The secondary objectives are to assess the effects of study treatments on (i) all-cause mortality 
among patients (ii) and on patients not on invasive mechanical ventilation at baseline, the 

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composite endpoint of death or need for invasive mechanical ventilation or ECMO. 
Furthermore, other objectives include (iii) the assessment of the effect of study treatments on 
the need for any ventilation (and duration of invasive mechanical ventilation), (iv) renal 
replacement therapy and (v) thrombotic events will be studied. Additionally, (vi) quality of life 
and (vii)  potential cardiac and neurological outcome after discharge and (viii) vaccine coverage 
will be assessed. 
 
5. Study outcomes 
Study outcomes will be assessed based on data recorded up to 28 days and up to 6 months 
after randomization. Furthermore, data from clinical routine-monitoring will be studied (1-2 
weeks after discharge, 4-6 weeks after discharge and 3 months after discharge) if clinical 
routine controls are indicated. 
 
5.1 Primary Outcome 
For children with PIMS-TS the hospital length of stay is the primary outcome. 
 
5.2 Secondary Outcomes 
Secondary outcomes include (i) all-cause mortality, (ii) the hospitalisation status, (iii) the 
use of ventilation including days of use and type and (iv) the use of renal dialysis or 
hemofiltration and (v) thrombotic events at 28 days after randomisation. Furthermore, (vi) 
quality of life and (vii) potential cardiac and neurological long-term impacts of PIMS-TS and 
influence of different pharmacological interventions and (v) thrombotic events will be 
included.  
6. Study design 
6.1 General study design 
The Swissped-Recovery is a sister trial of RECOVERY. The protocol describes an overarching 
trial design to provide reliable evidence on the efficacy of candidate therapies for children 
hospitalised with PIMS-TS receiving standard of care. It is an adaptive pragmatic platform trial 
with an open-label randomisation as described below. New trial arms can be added as 
evidence emerges that other candidate therapeutics should be evaluated. 
The protocol is deliberately flexible so that it is suitable for a wide range of settings, allowing: 
- 
a broad range of patients to be enrolled in large numbers; 
- 
randomisation between only those treatment arms that available at the hospital and not 
believed by the enrolling doctor to be contraindicated (e.g. by particular co-morbid 
conditions or concomitant medications); 
- 
treatment arms to be added or removed according to the emerging evidence; and 
additional substudies may be added to provide more detailed information on side 
effects or sub-categorisation of patient types but these are not the primary objective 
and are not required for participation. 
 
6.2. Randomization 
Eligible children with PIMS-TS will be randomized 1:1 to methylprednisolone 10 mg/kg 
intravenous versus intravenous immunoglobulins (IVIG). The patients will not be randomized 
to other treatment arms specified in section 2.4 of the International Protocol. For patients for 
whom not all the trial arms are appropriate or at locations where not all trial arms are available, 
the randomization will be between fewer arms. 
The randomization module for SWISSPED-RECOVERY will be identical with that used in the 
RECOVERY trial in the UK for the randomization stage. The relevant code has been shared 

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with a trial statistician from SWISSPED-RECOVERY. Randomization will occur online with 
allocated treatment displayed on screen and available for download. 
 
7. Study population 
Pediatric patients are eligible for the study if they fulfil the inclusion criteria.  
7.1.Inclusion criteria 
- 
Hospitalised children (aged <18 years old) 
- 
SARS-CoV-2 infection associated disease (clinically suspected or laboratory 
confirmed) with evidence of single or multi-organ dysfunction (called Pediatric 
Multisystem Inflammatory Syndrome temporally associated with COVID-19 [PIMS-
TS]).  
- 
No medical history that might, in the opinion of the attending clinician, put the patient 
at significant risk if he/she were to participate in the trial  
 
Exclusion criteria are specified accordingly: 
7.2. Exclusion criteria 
- 
Neonates/infants with a corrected gestational age of <= 44 weeks 
- 
If the attending clinician believes that there is a specific contra-indication to one of the 
active drug treatment arms or that the patient should definitely be receiving one of the 
active drug treatment arms, then the patient will not be available for randomisation. 
 
7.3 Recruitment and screening 
Eligible children will be identified continuously in the emergency department, paediatric wards, 
and intensive care units of participating paediatric centres by assessment against the eligibility 
criteria as listed above. Eligibility will be reviewed and documented by an appropriately trained 
member of staff delegated by the site PI. 
 
7.4 Consent process 
Trained investigators and local staff will explain to each participant the nature of the study, its 
purpose, the procedures involved, the expected duration, the potential risks and benefits and 
any discomfort it may entail. It will be made completely and unambiguously clear that the 
parent/guardian of a child is free to refuse to participate in all or any aspect of the trial, at any 
time and for any reason, without incurring any penalty or affecting the treatment of their child. 
The family will be informed that their child’s medical records will be examined by authorized 
persons other than their treating physician to ascertain trial outcomes. 
 
All participants for the study will be provided a participant information sheet and a consent form 
describing the study and providing sufficient information for participant to make an informed 
decision about their participation in the study. Informed consent should be obtained from legal 
representatives/parents (children < 18 years). In addition, children aged ≥ 14 years should give 
a written consent. The patient or the next of skin do not always have the capacity to give their 
consent for the study in advance or at all. In this study included patients will mostly be 
emergency cases. If the patient/parent lack capacity to give consent due to the severity of their 
medical condition (e.g. acute respiratory failure or need for immediate ventilation) or prior 
disease, then consent may be obtained from a relative acting as the patient’s legally 
designated representative. If no suitable relative is available after reasonable efforts to locate 
one, an independent doctor will declare the patients` suitability for trial participation. As such, 
the independent physician safeguards the participant interest and insures proper medical care. 
The signed document of the independent physician is the prevailing condition for inclusion of 

Version 1.3, 18 January 2022 
 
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the patient in our study. Informed consent will then be sought with the patient or a parent, if 
they recover sufficiently.  
 
The participant should read and consider the statement before signing and dating the informed 
consent form, and should be given a copy of the signed document. The consent form must 
also be signed and dated by the investigator (or his designee) at the same time as the 
participant signs, and a copy retained as part of the study records. 
Deferred or witnessed consent as outlined in section 2.2 of the International Protocol may be 
used in exceptional circumstances. 
 
The formal consent of a participant, using the approved consent form, will be obtained before 
the participant is submitted to any study procedure. In addition, the parent/guardian of the child 
will be informed about the possibility of re-use of health-related data and samples from this 
trial for other research project. They can consent in a separate form. 
 
7.5 Criteria of withdrawal/discontinuation of participants 
The patient or the legal representative has the right to withdrawal at any time point without 
specifying any reasons for withdrawal. 
Subjects may be withdrawn because of the appearance of a new health condition requiring 
care or medications prohibited by the protocol, unacceptable adverse event, refusal to continue 
treatment, or at the Investigator’s discretion if it is in the subject’s best interest. In case a patient 
or a parent will withdrawal the informed consent or the informed consent will not be given after 
primary witness consent, the data and samples will be used until time of withdrawal to assure 
the scientific quality of the trial. After analyse the data will be anonymized and the left-over of 
samples will be destroyed.  
 
8. Statistical methods 
8.1 Hypothesis 
Null hypothesis: Mean length of stay is the same for methylprednisolone 10 mg/kg as that on 
the other treatment  
Alternative Hypothesis: Mean length of stay on the methylprednisolone 10 mg/kg arm is not 
the same as that on the other treatment (two sided). 
 
8.2 Determination of Sample size 
The larger the number randomized the more accurate the results will be, but the numbers that 
can be randomized will depend critically on the progress of the epidemic and the influence of 
vaccination on children/family groups.  For the 13 months period of the trial, we estimate that 
between approximately 50 and 120 children across the 10 centres can be recruited. According 
to expert opinion, the best estimate (i.e. the mode) would be approximately 80 children 
assigned to each of the arms using 1:1 randomization (i.e 40 in each arm). Accordingly, for the 
primary endpoint comparing mean log transformed length of stay for those on 
methylprednisolone 10 mg/kg (N=40) to those on intravenous immunoglobulins (N=40) using 
a two-sided t-test and with a 5% significance level, we would be able to detect a normalized 
effect size of approximately 0.65 with 80% power.  
 
8.3 Statistical considerations  
For all outcomes, comparisons will be made between all participants randomised to the 
different treatment arms, irrespective of whether they received their allocated treatment 

Version 1.3, 18 January 2022 
 
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(“intention-to-treat” analyses). 
For the primary endpoint, the log transformed time to discharge (or death) will be compared 
between those on methylprednisolone 10 mg/kg and those on intravenous immunoglobulins 
For time-to-event analyses, each treatment group will be compared using the log-rank test. 
Kaplan-Meier estimates for the time to event will also be plotted (with associated log-rank p-
values). For binary outcomes where the timing is unknown, the risk ratio and absolute risk 
difference will be calculated with confidence intervals and p-value reported. For the time to 
event endpoints, discharge alive before 28 days will assume safety from the event (unless 
there is additional data confirming otherwise). 
Allowance for multiple treatment comparisons due to the design will be made.  A p-value of 
less than 0.05 will be considered statistically significant throughout. 
 
9. Study assessments and Data collection 
At randomization, information of the patients will be collected (e.g. age, sex, major co-
morbidities) and any contraindications to the study treatments. Additional baseline information 
such as patient`s health conditions will be collected and recorded on the web-based case 
report form by the attending clinician or delegated study personal. Follow-up information will 
be ascertained (i) at day 28 after first randomization or (ii) at discharge or (iii) death (whichever 
is sooner) (please refer to figure 1).   
 
Figure 1: Study assessment and data collection at randomization/baseline and after 28 days, 
discharge or death (which is sooner) 
 
After discharge/day 28 follow-up information will be collected on all study participants at each 
site during clinical routine follow-up visits (Figure 2). These clinical follow-up visits are routinely 
scheduled at 1-2 weeks, 4-6 weeks, and 3-6 months post discharge. During these clinical 
routine visits, usually a clinical examination, a laboratory assessment and an 
echocardiography is performed. Individual modification according to the clinician decisions are 
possible. For these follow-up visits the data collection will be from routine clinical records. 
 

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Figure 2: Study assessment and data collection at follow-up 
 
Local substudies 
Post-discharge follow-up: Quality of Life, post-traumatic stress disorder, and measures of 
functional recovery such as school attendance up to six months post PIMS-TS diagnosis will 
be evaluated. Cardiac function and presence of coronary artery aneurysms will be assessed 
by echocardiography.  
 
 
 
Figure 3: Sub study Quality of Life, post-traumatic stress disorder, and measures of functional 
recovery paired with vaccine coverage. 

Version 1.3, 18 January 2022 
 
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Health care costs: Direct hospitalization-related costs will be captured for health economic 
analyses. For each PIMS-TS related hospitalization episode recruited in the study, the total 
Diagnosis-Related Group (DRG) costs claimed by the respective study site will be extracted 
from the institutional finance records, and analysed in batch upon completion of recruitment. 
 
Data collection 
A simplified study schedule including data of interest and follow-up visits is shown below. For 
further specification of the data of interest, please see sections 2.3 And 2.7 of the International 
Protocol. Data collection will be from routine clinical records, except for the extended follow-
up.  
 
Study schedule 
 
Enrolment Randomization Final 
visit 
Extended 
f/u 
Days in trial 
0 
1 
281 
At routine 
outpatient 
follow-up 
Trial participation 
 
Eligibility screen 
X 
 
 
 
Patient/parent information sheet 
X° 
 
 
 
Informed consent 
X° 
 
 
 
Trial intervention first randomization 
 
X 
 
 
Trial 
intervention 
second 
randomization 
 
X 
 
 
Clinical assessments 
 
Acute and past medical history  
 
X 
 
X 
Vital signs 
 
X 
 
 
Treatment included in RECOVERY  
 
X 
X 
 
Supportive/directed treatment 
 
X 
X 
 
Specified adverse events 
 
X 
X 
 
Concomitant 
care/ 
Healthcare 
utilization 
 
X 
X 
X 
Disposition/outcome 
 
 
X 
 
Quality of Life assessments 
 
 
  
X 
Vaccine coverage data 
 
 
 
x 
Laboratory assessments 
 
SARS-CoV-2 diagnostics 
(X) 
(X) 
(X) 
 
Haematology 
(X) 
(X) 
(X) 
 
Biochemistry 
(X) 
(X) 
(X) 
 
Imaging  
 
Chest X-ray 
(X) 
(X) 
(X) 
 
Echocardiography 
(X) 
(X) 
(X) 
X 
1recorded at discharge, upon death or at 28 days (whichever is sooner) 
X° Witnessed or deferred consent may be used in exceptional cases. 
 (X) indicates tests that may be done based on clinical assessment. Results will be collected, 
if available. 
Light grey shading: only relevant for substudies. 
 

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10. Regulatory aspects and safety 
10.1 Definition and assessment of (serious) adverse events and other safety related events 
An Adverse Event (AE) is any untoward medical occurrence in a patient or a clinical 
investigation participant administered a pharmaceutical product and which does not 
necessarily have a causal relationship with the study procedure. An AE can therefore be any 
unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or 
disease temporally associated with the use of a medicinal (investigational) product, whether 
or not related to the medicinal (investigational) product. [ICH E6 1.2] 
A Serious Adverse Event (SAE) is classified as any untoward medical occurrence that: 
• 
results in death, 
• 
is life-threatening, 
• 
requires in-patient hospitalization or prolongation of existing hospitalisation 
• 
results in persistent or significant disability/incapacity, or 
• 
is a congenital anomaly/birth defect 
In addition, important medical events that may not be immediately life-threatening or result in 
death, or require hospitalisation, but may jeopardise the patient or may require intervention to 
prevent one of the other outcomes listed above should also usually be considered serious. 
[ICH E2A]. 
SAEs should be followed until resolution or stabilisation. Participants with ongoing SAEs at 
study termination (including safety visit) will be further followed up until recovery or until 
stabilisation of the disease after termination.  
 
Assessment of Causality 
Both Investigator and Sponsor-investigator make a causality assessment of the event to the 
study drug, based on the criteria listed in the ICH E2A guidelines: 
Relationship 
Description 
Definitely 
Temporal relationship 
Improvement after dechallenge* 
Recurrence after rechallenge 
(or other proof of drug cause) 
Probably 
Temporal relationship 
Improvement after dechallenge 
No other cause evident 
Possibly 
Temporal relationship 
Other cause possible 
Unlikely 
Any assessable reaction that does not fulfil the above 
conditions 
Not related 
Causal relationship can be ruled out 
*Improvement after dechallenge only taken into consideration, if applicable to reaction 
 
 

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Unexpected Adverse Drug Reaction 
An “unexpected” adverse drug reaction is an adverse reaction, the nature or severity of 
which is not consistent with the applicable product information (e.g. Investigator’s Brochure 
for drugs that are not yet approved and Product Information for approved drugs, 
respectively). [ICH E2A] 
 
Suspected Unexpected Serious Adverse Reactions (SUSARs) 
The Sponsor-Investigator evaluates any SAE that has been reported regarding seriousness, 
causality and expectedness. If the event is related to the investigational product and is both 
serious and unexpected, it is classified as a SUSAR 
 
10.2 Reporting of serious adverse events (SAE) and other safety related events 
The focus on severe adverse event (SAE) is on those events are likely to be related with the 
study medication. Examples include anaphylaxis, Steven Johnson Syndrome or bone marrow 
failure, where there is no other plausible explanation. Anticipated events, including SAEs, that 
are either efficacy endpoints or consequences of the underlying disease will be exempted from 
expedited reporting. Thus, the following events will be exempted from expedited reporting:  
(i) Events which are the consequence of COVID-19; and  
(ii) Common events which are the consequence of conditions preceding randomisation.  
 
If a SAE occurs, it will be reported within a maximum of 24 hours to the Sponsor-Investigator 
of the study. The Sponsor-Investigator will re-evaluate the SAE. SAEs resulting in death are 
reported to the Ethics Committee via BASEC within 7 days. The other in the trial involved 
Ethics Committees receive SAEs resulting in death in Switzerland via Sponsor-Investigator via 
BASEC within 7 days.  
 
A SUSAR needs to be reported to the Ethics Committee (local event via local Investigator) via 
BASEC within 7 days, if the event is fatal, or within 15 days (all other events). The Sponsor-
Investigator must inform all Investigators participating in the clinical study of the occurrence of 
a SUSAR. All in the trial involved Ethics Committees will be informed about SUSARs in 
Switzerland via Sponsor-Investigator via BASEC according to the same timelines.  
 
If a sub-protocol or arm is closed early by the sponsor due to a non-favourable benefit-risk 
balance, the end of such part of the trial should be communicated as an urgent safety measure 
or as a substantial amendment related to an urgent safety measure. The reason for the early 
termination and implication for the trial subjects, including description of any intended follow-
up activities, should be provided in both cases Urgent safety measure will be reported via 
BASEC within 7 days according to Art. 37 KlinV.  
Substantial changes to the project set-up, the protocol and relevant project documents will be 
submitted to the Ethics Committee for approval according to KlinV Art. 29 before 
implementation. Exceptions are measures that have to be taken immediately in order to protect 
the participants. 
Upon project discontinuation, the Ethics Committee is notified within 15 days. Upon project 
completion, the Ethics Committee is notified within 90 days.  
 
 
 

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11. Quality control and data protection 
The Pediatric Research Centre at UKBB will implement a quality control system on behalf of 
the sponsor-investigator to ensure adherence to study procedures at all study sites and monitor 
the conduct of the study. Written standard operating procedures (SOPs) and a manual of 
operations will be issued to all sites. 
All data collected for central analysis in the study, whether clinical data recorded in the 
electronic data capture (EDC) system or other data, will be coded by a unique randomly 
generated participant study ID. All personnel involved will be trained in project-related 
procedures and all-important aspects, including data entry. A project-specific delegation log 
will be kept to document training and project-related specific responsibilities of staff members. 
For quality assurance the Ethics Committee may visit the research sites. Direct access to the 
source data and all project related files and documents must be granted on such occasions. 
Relevant clinical study data for each enrolled study participant, i.e. observations, tests and 
assessments specified in the protocol, are recorded via the web-based EDC system in 
REDCapTM. The REDCapTM database is accessible via the internet. Electronic access is strictly 
controlled using role-based access permissions defined by the local REDCapTM administrator 
and by the Principal Investigator. The data are stored on a firewall-protected UKBB server and 
regularly backed up. All data modifications can be identified through a complete audit trail. 
Local investigators registered with the sponsor-investigator will be authorized for the eCRF 
entries of study participants enrolled at the site. Investigators will be trained to use the EDC 
system during the site initiation visit. The investigators ensure the accuracy, completeness, 
and timeliness of the data recorded and provide answers to data queries, as specified in the 
study protocol and in accordance with additional instructions. The identity of the local 
investigator entering data and date and time of data entry will be recorded as meta-data in the 
study database. 
The local investigator is required to maintain an accurate medical record of all original 
documents and data relevant to the study as source documentation. The participant study ID 
will be noted in the patients’ medical record and a copy of the signed informed consent form 
will be filed in the medical record to identify study participants locally at the study site.  
All project data will be handled in accordance with the Ordinance to the Federal Act on Data 
Protection (DPO) of 14 June 1993 and with uttermost discretion. It is only accessible to 
authorized personnel who require the data to fulfil their duties within the scope of the research 
project. All personal and medical information obtained for this study is confidential and 
disclosure to third parties other than those essential to the implementation of the project or 
noted below is prohibited.  
Clinical source data will be kept at the study sites in the patients’ medical records and include 
demographic and clinical data, medical history, prescribed medication during admission, all 
clinical examinations and all laboratory and radiological evaluations undertaken as part of 
routine clinical care. Data which are directly recorded in the eCRF will also be considered as 
source documents and include detailed documentation of all study eligibility criteria as well as 
a confirmation that the participant has signed the informed consent form. 
All study data will be archived for a minimum of 10 years after study termination or premature 
termination of the clinical trial. Study-relevant source data and documents will be archived at 
study sites for a minimum of 10 years. 
 
12. Monitoring 
At each participating site, the principal investigator will confirm that the site has adequate 
facilities and resources to carry out the study. The sponsor-investigator, representatives of the 
trial management team and a designated external study monitor will conduct a site initiation 

Version 1.3, 18 January 2022 
 
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visit at each study site to inspect the site facilities, verify qualifications of the local investigators 
and inform the local teams of responsibilities and the procedures for ensuring adequate and 
correct documentation and use of the EDC system as well as providing training on 
implementing all trial activities. 
As outlined in the main protocol, monitoring visits at sites are not envisaged. In exceptional 
circumstances, an onsite monitoring visit may be arranged as considered appropriate based 
on perceived training needs and the results of central data-based monitoring. 
 
13. Funding 
This research project is an investigator-initiated project. We are currently seeking funding from 
charitable foundations to provide site and trial team support. The study has been endorsed by 
SwissPedNet. We declare no conflict of interest (independence, intellectual, financial, 
proprietary).