Clinical Trial Results:
A Phase 3 Open-label, Single Arm Study to Evaluate the Safety and Efficacy of Pembrolizumab (MK- 3475) as First-line Therapy in Participants With Advanced Merkel Cell Carcinoma (KEYNOTE-913)
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Summary
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EudraCT number |
2018-002601-57 |
Trial protocol |
SE FR ES IT |
Global end of trial date |
15 Feb 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
31 Jan 2025
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First version publication date |
31 Jan 2025
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
MK-3475-913
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Additional study identifiers
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ISRCTN number |
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US NCT number |
NCT03783078 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
KEYNOTE-913: MSD | ||
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Sponsors
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Sponsor organisation name |
Merck Sharp & Dohme LLC
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Sponsor organisation address |
126 East Lincoln Avenue, P.O. Box 2000, Rahway, NJ, United States, 07065
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Public contact |
Clinical Trials Disclosure, Merck Sharp & Dohme LLC, ClinicalTrialsDisclosure@msd.com
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Scientific contact |
Clinical Trials Disclosure, Merck Sharp & Dohme LLC, ClinicalTrialsDisclosure@msd.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
15 Feb 2024
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
15 Feb 2022
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Global end of trial reached? |
Yes
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Global end of trial date |
15 Feb 2024
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
This was a single-arm, open-label, multicenter, efficacy, and safety study of pembrolizumab in adult and pediatric participants with previously untreated advanced Merkel Cell Carcinoma (MCC). The primary objective of the trial was to assess the objective response rate, as assessed by blinded independent central review per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, following administration of pembrolizumab.
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Protection of trial subjects |
This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human participants participating in biomedical research.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
25 Feb 2019
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Australia: 3
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Country: Number of subjects enrolled |
Canada: 4
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Country: Number of subjects enrolled |
France: 17
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Country: Number of subjects enrolled |
Italy: 14
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Country: Number of subjects enrolled |
New Zealand: 3
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Country: Number of subjects enrolled |
Spain: 5
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Country: Number of subjects enrolled |
Sweden: 8
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Country: Number of subjects enrolled |
United States: 1
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Worldwide total number of subjects |
55
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EEA total number of subjects |
44
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
12
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From 65 to 84 years |
36
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85 years and over |
7
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Recruitment
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Recruitment details |
- | ||||||||||||||||
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Pre-assignment
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Screening details |
Participants of at least 12 years of age with advanced Merkel cell carcinoma (MCC) were recruited to evaluate the safety and efficacy of Pembrolizumab (MK-3475) as first-line therapy. A total of 55 participants from 8 countries were enrolled. | ||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||
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Arms
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Arm title
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Pembrolizumab 200 mg | ||||||||||||||||
Arm description |
Adult participants received pembrolizumab (MK-3475) 200 mg or pediatric participants received 2 mg/kg (up to 200 mg) on Day 1 of each 3-week cycle (Q3W) intravenously (IV), for up to 35 administrations (approximately 2 years). | ||||||||||||||||
Arm type |
Experimental | ||||||||||||||||
Investigational medicinal product name |
Pembrolizumab
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Investigational medicinal product code |
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Other name |
MK-3475
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Pembrolizumab (MK-3475) 200 mg (adult participants) or 2 mg/kg (up to 200 mg; pediatric participants) on Day 1 of each 3-week cycle (Q3W) intravenous (IV), for up to 35 administrations (approximately 2 years)
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Baseline characteristics reporting groups
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Reporting group title |
Pembrolizumab 200 mg
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Reporting group description |
Adult participants received pembrolizumab (MK-3475) 200 mg or pediatric participants received 2 mg/kg (up to 200 mg) on Day 1 of each 3-week cycle (Q3W) intravenously (IV), for up to 35 administrations (approximately 2 years). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Pembrolizumab 200 mg
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Reporting group description |
Adult participants received pembrolizumab (MK-3475) 200 mg or pediatric participants received 2 mg/kg (up to 200 mg) on Day 1 of each 3-week cycle (Q3W) intravenously (IV), for up to 35 administrations (approximately 2 years). | ||
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End point title |
Objective Response Rate (ORR) [1] | ||||||||
End point description |
ORR was defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). The percentage of participants who experienced CR or PR as assessed by blinded independent central review (BICR) were presented. The analysis population consisted of all allocated participants who received at least 1 dose of study treatment.
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End point type |
Primary
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End point timeframe |
Up to ~34 months
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses were planned for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of Participants Who Discontinued From Study Treatment Due to an AE | ||||||
End point description |
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinued from study treatment due to an AE was assessed. The analysis population consisted of all allocated participants who received at least one dose of study treatment.
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End point type |
Secondary
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End point timeframe |
Up to ~27 months
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| No statistical analyses for this end point | |||||||
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End point title |
Overall Survival (OS) | ||||||||
End point description |
OS was defined as the time from the first dose of study treatment until death from any cause. The analysis population consisted of all allocated participants who received at least 1 dose of study treatment. A value of 9999 means the upper limit was not reached at time of data cut-off due to insufficient number of participants with an event.
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End point type |
Secondary
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End point timeframe |
Up to ~58 months
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of Participants with One or More Adverse events (AEs) | ||||||
End point description |
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants with at least one AE was assessed. The analysis population consisted of all allocated participants who received at least one dose of study treatment.
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End point type |
Secondary
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End point timeframe |
Up to ~58 months
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| No statistical analyses for this end point | |||||||
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End point title |
Duration of Response (DOR) | ||||||||
End point description |
For participants with a confirmed CR or PR per RECIST 1.1, DOR was the time from first documented evidence of CR or PR until progressive disease (PD) or death. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. Per RECIST 1.1, PD was at least a 20% increase in the sum of diameters of target lesions & an absolute increase of at least a 5 mm in the sum of diameters. The appearance of one or more new lesions was also considered PD. DOR assessments were based on BICR with confirmation. The DOR using RECIST 1.1 for all participants who experienced a confirmed CR or PR was presented. The analysis population consisted of all allocated participants who received at least 1 dose of study treatment, and who experienced a confirmed CR or confirmed PR. A value of 9999 means the upper limit not reached at time of data cut-off due to insufficient number of responding participants with relapse.
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End point type |
Secondary
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End point timeframe |
Up to ~58 months
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| No statistical analyses for this end point | |||||||||
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End point title |
Progression-free Survival (PFS) | ||||||||
End point description |
Progression-Free Survival was defined as the time from the first dose of study treatment to the first documented evidence of disease progression per RECIST 1.1 by BICR or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. PFS as assessed by BICR per RECIST 1.1 was presented. The analysis population consisted of all allocated participants who received at least 1 dose of study treatment.
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End point type |
Secondary
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End point timeframe |
Up to ~58 months
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Up to ~58 months
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Adverse event reporting additional description |
All-cause mortality includes all participants. AEs include participants who received ≥1 dose of study treatment. Disease progression was not considered an AE unless related to study treatment. MedDRA preferred terms "Neoplasm progression" "Malignant neoplasm progression" and "Disease progression" not related to study treatment were excluded as AEs.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
26.1
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Reporting groups
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Reporting group title |
Pembrolizumab 200 mg
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Reporting group description |
Adult participants received pembrolizumab (MK-3475) 200 mg or pediatric participants received 2 mg/kg (up to 200 mg) on Day 1 of each 3-week cycle (Q3W) intravenously (IV), for up to 35 administrations (approximately 2 years). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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19 Nov 2020 |
Amendment 1: The primary reasons for the amendment were to implement country-specific changes, make procedural updates, clarify objective response rate, and remove of substudy references for Future Biomedical Research. |
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28 Jul 2021 |
Amendment 2: The primary reasons for the amendment were to harmonize the presentation of safety information across all Food and Drug Administration-approved programmed cell death 1/programmed cell death ligand 1 antibody prescribing information and to update imaging frequency. |
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09 Aug 2022 |
Amendment 3: The primary reason for the amendment was to update the Sponsor's name. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
