Clinical Trial Results:
A phase II trial assessing nivolumab in strong class II expressing microsatellite stable colorectal cancer
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Summary
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EudraCT number |
2018-000318-39 |
Trial protocol |
GB |
Global end of trial date |
27 Nov 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
13 May 2026
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First version publication date |
13 May 2026
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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 |
RG_17-215
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Additional study identifiers
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ISRCTN number |
ISRCTN40245896 | ||
US NCT number |
NCT03981146 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
University of Birmingham
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Sponsor organisation address |
Edgbaston, Birmingham, United Kingdom, B15 2TT
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Public contact |
Joshua Savage, University of Birmingham, anicca-classII@trials.bham.ac.uk
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Scientific contact |
Joshua Savage, University of Birmingham, anicca-classII@trials.bham.ac.uk
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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 |
14 Feb 2025
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
26 Nov 2024
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Global end of trial reached? |
Yes
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Global end of trial date |
27 Nov 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 |
The primary objective of this trial is to detect the rate of durable clinical benefit in patients with strong class II expressing Micro Satellite Stable Colorectal Cancer treated with single agent nivolumab, to justify further investigation in subsequent studies.
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Protection of trial subjects |
The Trial Steering Committee (TSC) provides overall supervision for the trial on behalf of the Trial Sponsor (University of Birmingham) and to ensure that the trial is conducted to the rigorous standards set out in the GCP standards. In particular, the TSC will concentrate on progress of the trial, adherence to the protocol, patient safety, evidence on main efficacy outcome measures and the consideration of new information of relevance to the research question. The safety and well-being of the trial participants are the most important considerations and should prevail over the interests of science and society. The TSC will provide advice, through its Chair, to the Chief Investigator and the University of Birmingham on all appropriate aspects of the trial. Membership of the TSC includes an independent Chair and two other independent members, who do not sit on the TMG, including a Patient, Public & Involvement (PPI) representative. The TSC will be asked to comment in detail on substantial changes to the protocol. The TSC will meet as often as required, at least once per year during recruitment.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
28 Aug 2019
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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 |
United Kingdom: 35
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Worldwide total number of subjects |
35
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EEA total number of subjects |
0
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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) |
23
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From 65 to 84 years |
12
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85 years and over |
0
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Recruitment
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Recruitment details |
The trial opened to recruitment on 28th August 2019 with the first patient screened on 4th September 2019 and the first patient registered on 3rd August 2020. The last patient was recruited on 5th August 2021 and the trial closed to recruitment on 6th September 2021. | ||||||
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Pre-assignment
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Screening details |
464 patients consented for determination of microsatellite (MSS) & class II status. 457 provided a screening biopsy for testing, which was performed centrally at Queen Elizabeth Hospital Birmingham (University Hospitals Birmingham NHS Foundation Trust). This was successful in 444 (97%) patients, 58 were confirmed to have MSS class II expression. | ||||||
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Period 1
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Period 1 title |
Overall trial (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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Nivolumab | ||||||
Arm description |
Nivolumab will be administered as a 60 minute IV infusion, with a window of -5 and +10 minutes, at a flat dose of 480mg. A dosing interval every 4 weeks (Q4W) was employed. Patients could receive nivolumab for a maximum of 2 years, or until disease progression, unacceptable toxicity or withdrawal of consent. With the first dose, cycle 1 day 1, to be given within 7 days of registration to the trial. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Nivolumab
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Investigational medicinal product code |
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Other name |
Opdivo
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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 |
Nivolumab was provided as vials containing 10 mg/mL concentrate of drug substance in solution for infusion. Administered as a 60 minute IV infusion, with a window of -5 and +10 minutes, at a flat dose of 480mg. A dosing interval every 4 weeks (Q4W) was employed. Patients could receive nivolumab for a maximum of 2 years, or until disease progression, unacceptable toxicity or withdrawal of consent. With the first dose, cycle 1 day 1, to be given within 7 days of registration to the trial.
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Nivolumab
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Reporting group description |
Nivolumab will be administered as a 60 minute IV infusion, with a window of -5 and +10 minutes, at a flat dose of 480mg. A dosing interval every 4 weeks (Q4W) was employed. Patients could receive nivolumab for a maximum of 2 years, or until disease progression, unacceptable toxicity or withdrawal of consent. With the first dose, cycle 1 day 1, to be given within 7 days of registration to the trial. | ||
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End point title |
Durable Clinical Benefit [1] | ||||||||||
End point description |
Patient will be defined as experiencing DCB if they remain free of disease progression at their third trial specific CT scan since treatment start date (i.e. at approximately 27 weeks) or at any CT scan after 27 weeks that shows the patient remains free of disease progression
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End point type |
Primary
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End point timeframe |
Beginning of trial treatment to free of disease progression (104 weeks maximum)
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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: There is no statistical comparison for this single arm trial. The median of the posterior probability distribution for the true DCB rate was used to provide a Bayesian estimate of the DCB rate and 95% CrI. The anaysis conducted was a beta-binomial conjugate analysis using a Beta(1, 1) prior, this resulted in a bayesian estimate of DCB of 0.11 (95% CrI: 0.03, 0.22). 3 patients who reported durable clinical benefit, this resulted in a 0.002 probability that the true DCB rate was >= to 30%. |
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| No statistical analyses for this end point | |||||||||||
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End point title |
Objective Response | ||||||||||
End point description |
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) assessed by CT scan, objective response is the occurrence of Complete Response (CR) or Partial Response (PR) as the best overall response. Best overall response is the combined evaluation of target and non-target lesions, as provided in the protocol appendix 3.
Target lesions are evaluated as Complete Response (CR; disappearance of all target lesions), Partial Response (PR; >=30% decrease in the sum of the longest diameter), Progressive Disease (PD; >=20% increase in the sum of the longest diameter) or Stable Disease (SD; insufficient shrinkage for PR or insufficient increase for PD).
Non-target lesions are evaluated as Complete Response (CR; disappearance of all non-target lesions), Incomplete Response/Stable Disease (SD; persistence of non-target lesions) or Progressive Disease (PD; new lesions and/or progression of existing non-target lesions).
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End point type |
Secondary
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End point timeframe |
Trial treatment until disease progression (104 weeks maximum)
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| No statistical analyses for this end point | |||||||||||
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End point title |
Best Percentage Change in Sum of Target Lesions | ||||||||
End point description |
At each evaluation, the longest diameters of all selected target lesions will be measured and summed and the percentage change from the baseline measurement will be calculated. The best percentage change is the one that reflects either the greatest decrease or the least increase over the whole period of assessment.
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End point type |
Secondary
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End point timeframe |
Trial Treatment to disease progression (104 weeks maximum)
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| Notes [2] - Only 30 had CT scans following baseline assessment, so this outcome could not be measured for 5 pts. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Progression free survival time | ||||||||
End point description |
This is defined as the time from commencement of trial treatment to the date of CT scan when progressive disease first recorded or date of death without previously recorded progression.
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End point type |
Secondary
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End point timeframe |
Time from commencement of trial treatment to the date of CT scan when progressive disease first recorded (104 weeks maximum)
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| No statistical analyses for this end point | |||||||||
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End point title |
Overall Survival Time | ||||||||
End point description |
This is defined as the time from commencement of trial treatment to the date of death from any cause.
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End point type |
Secondary
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End point timeframe |
Commencement of trial treatment until date of death; minimum of 18 months post-registration, if trial treatment was discontinued early, or up to 24 months post-registration for those completing trial treatment.
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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 |
From the date of trial consent until 6 months after treatment discontinuation. If at the 6 month review time-point, any toxicities at grade 2 or higher related to trial treatment were still occurring, these were to be followed up until resolution.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
CTCAE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
4.03
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Reporting groups
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Reporting group title |
Nivolumab
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Reporting group description |
Nivolumab will be administered as a 60 minute IV infusion, with a window of -5 and +10 minutes, at a flat dose of 480mg. A dosing interval every 4 weeks (Q4W) was employed. Patients could receive nivolumab for a maximum of 2 years, or until disease progression, unacceptable toxicity or withdrawal of consent. With the first dose, cycle 1 day 1, to be given within 7 days of registration to the trial. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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02 Apr 2019 |
Substantial Amendment 1 (Protocol v3.0): Change to collect only month and year for date of birth. Clarification of follow-up period for pregnancies. |
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14 Nov 2019 |
Substantial Amendment 2 (Protocol v4.0): Addition of ISRCTN. Section 5.2: eRDC webpage amended. Addition of wording for new biopsy if archival biopsy is not sufficient or available. Change of PI at Beatson Cancer Centre. |
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20 May 2020 |
Substantial Amendment 3 (Protocol v5.0): Change in Class II expression requirements for eligibility. Addition of wording to allow treatment beyond progression if there is clinical benefit. Removal of fax number throughout. Clarification of pregnancy test requirements. Changes to assessment time points within the schedule of events to accommodate treatment dose changes. Change to treatment dose and schedule from 2 to 4 weekly. Addition of exploratory objective. |
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24 Aug 2021 |
Substantial Amendment 6 (Protocol v6.0): Changes to Table 3: Dose modification and toxicity management guidelines for immune-related AEs associated with nivolumab to include guidance from SPC (24-Aug-2020). Text added to schedule of assesments to clarify when an isotopic EGFR is needed. Text added to schedule of assesments to clarify the date that CT scans should be scheduled from. Schedule of Assessment tables updated to reflect that where applicable and acceptable in accordance to local practices, visits/assesments may be performed by telephone or video call. Process for remote consent added. Information relating to COVID-19 added. |
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01 Nov 2021 |
Substantial Amendment 8 (Protocol v7.0): Changes to Table 3 : Dose modification and toxicity management guidelines for immune-related AEs associated with nivolumab to include guidance from SPC. |
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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 | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/41407398 |
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