Clinical Trial Results:
A Prospective, randomised placebo controlled feasibility trial of Faecal Microbiotica Transplantation in cirrhosis
Summary
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EudraCT number |
2017-003629-13 |
Trial protocol |
GB |
Global end of trial date |
17 Oct 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
15 Oct 2020
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First version publication date |
15 Oct 2020
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Other versions |
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Summary report(s) |
Clinical Study report |
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 |
PROFIT
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02862249 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
King's College London
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Sponsor organisation address |
The Strand, London, United Kingdom, WC2R 2LS
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Public contact |
Professor Debbie Shawcross, King's College London, 44 2032993713, debbie.shawcross@kcl.ac.uk
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Scientific contact |
Professor Debbie Shawcross, King's College London, 44 2032993713, debbie.shawcross@kcl.ac.uk
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Sponsor organisation name |
King's College Hospital NHS Foundation Trust
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Sponsor organisation address |
Denmark Hill, London, United Kingdom, SE5 9RS
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Public contact |
Professor Debbie Shawcross, King's College London, 44 2032993713, debbie.shawcross@kcl.ac.uk
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Scientific contact |
Professor Debbie Shawcross, King's College London, 44 2032993713, debbie.shawcross@kcl.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 |
01 Dec 2019
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
17 Oct 2019
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Global end of trial reached? |
Yes
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Global end of trial date |
17 Oct 2019
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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 |
To assess whether stabilising gut dysbiosis with FMT in patients with advanced cirrhosis is both feasible and safe
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Protection of trial subjects |
A trial participant has the liberty to withdraw their consent at any time and for any reason, without penalty or loss of benefits to which the individual would otherwise be entitled. Participants who withdraw consent will discontinue their participation in the trial and no further data will be collected. Prior to giving consent, recipients will be informed that they are able to request the destruction of stored biological samples (e.g. blood/stool) upon withdrawal, and that this will only be possible for samples that have not been tested at the time of withdrawal. Participants will not be able to request the deletion of data generated from tested samples.
The DMEC’s role was to ensure safety of trial participants and review the interim data to ensure safety of trial continuation.
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Background therapy |
Patients received 2L of Moviprep®, one litre at 6pm the night before the endoscopy and the second litre at 6am on the morning of the endoscopy. Patients were required to be nil by mouth for 6 hours prior to the endoscopy. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
23 May 2018
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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: 23
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Worldwide total number of subjects |
23
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EEA total number of subjects |
23
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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) |
15
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From 65 to 84 years |
8
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85 years and over |
0
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Recruitment
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Recruitment details |
Thirty-two patients were recruited from outpatient clinics and the hepatology wards at King’s College Hospital, including two patients who were referred from Kingston Hospital. Subjects were recrited in a 12 month period from 23/05/2018. | |||||||||||||||
Pre-assignment
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Screening details |
At the screening visit consent forms signed and bloods checked for the MELD score and HIV serology. If the patient met the inclusion criteria, they attended the baseline visit where they were reviewed in the Clinical Research Facility by the research team. Concomitant medications, medical and surgical histories were confirmed. | |||||||||||||||
Pre-assignment period milestones
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Number of subjects started |
318 [1] | |||||||||||||||
Number of subjects completed |
23 | |||||||||||||||
Pre-assignment subject non-completion reasons
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Reason: Number of subjects |
ineligible: 286 | |||||||||||||||
Reason: Number of subjects |
Consent withdrawn by subject: 9 | |||||||||||||||
Notes [1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: Includes screen fails who were not enrolled in the study |
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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 |
Randomised - controlled
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Blinding used |
Single blind | |||||||||||||||
Roles blinded |
Subject | |||||||||||||||
Blinding implementation details |
IMP was delivered out of the patient’s sight, so as not to unblind them to the treatment allocation. All efforts were made to maintain blinding of the treatment allocation to the patient, but the study investigators were not blinded as the placebo and FMT solutions were not matched.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Faecal microbiota transplantation (FMT) | |||||||||||||||
Arm description |
Faecal microbiota transplantation (FMT) derived from a healthy donor (200mls- less small aliquot for archiving) administered via a gastroscope into the duodenum following preparation of the bowel with 2 sachets of MoviPrep® [PEG-3350, sodium sulphate, sodium chloride, potassium chloride, sodium ascorbate and ascorbic acid for oral solution 100g, 7.5g, 2.691g, 1.051g, 5.9g, 4.7g | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Faecal Microbiota for Transplantation
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Gastroenteral liquid
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Routes of administration |
Intraduodenal use
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Dosage and administration details |
190ml administered via a gastroscope into the duodenum following preparation of the bowel with 2 sachets of MoviPrep® [PEG-3350, sodium sulphate, sodium chloride, potassium chloride, sodium ascorbate and ascorbic acid for oral solution 100g, 7.5g, 2.691g, 1.051g, 5.9g, 4.7g].
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Arm title
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Placebo | |||||||||||||||
Arm description |
Placebo solution (200mls 0.9% normal saline and 12.5% glycerol) administered via a gastroscope into the duodenum following preparation of the bowel with 2 sachets of MoviPrep®. | |||||||||||||||
Arm type |
Placebo | |||||||||||||||
Investigational medicinal product name |
200mls 0.9% normal saline and 12.5% glycerol
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Gastroenteral liquid
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Routes of administration |
Intraduodenal use
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Dosage and administration details |
Placebo solution (200mls 0.9% normal saline and 12.5% glycerol) administered via a gastroscope into the duodenum following preparation of the bowel with 2 sachets of MoviPrep®.
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Baseline characteristics reporting groups
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Reporting group title |
Faecal microbiota transplantation (FMT)
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Reporting group description |
Faecal microbiota transplantation (FMT) derived from a healthy donor (200mls- less small aliquot for archiving) administered via a gastroscope into the duodenum following preparation of the bowel with 2 sachets of MoviPrep® [PEG-3350, sodium sulphate, sodium chloride, potassium chloride, sodium ascorbate and ascorbic acid for oral solution 100g, 7.5g, 2.691g, 1.051g, 5.9g, 4.7g | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Placebo solution (200mls 0.9% normal saline and 12.5% glycerol) administered via a gastroscope into the duodenum following preparation of the bowel with 2 sachets of MoviPrep®. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Faecal microbiota transplantation (FMT)
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Reporting group description |
Faecal microbiota transplantation (FMT) derived from a healthy donor (200mls- less small aliquot for archiving) administered via a gastroscope into the duodenum following preparation of the bowel with 2 sachets of MoviPrep® [PEG-3350, sodium sulphate, sodium chloride, potassium chloride, sodium ascorbate and ascorbic acid for oral solution 100g, 7.5g, 2.691g, 1.051g, 5.9g, 4.7g | ||
Reporting group title |
Placebo
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Reporting group description |
Placebo solution (200mls 0.9% normal saline and 12.5% glycerol) administered via a gastroscope into the duodenum following preparation of the bowel with 2 sachets of MoviPrep®. |
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End point title |
Assessment of Safety [1] | |||||||||||||||||||||
End point description |
Assessment of the safety of FMT:
• Incidence of any transmissable bacterial or viral infection that is deemed to have been acquired from the donor including Clostridiodes difficile infection.
• The development of any Serious Adverse Event (SAE), Serious Adverse Reaction (SAR) or Unexpected Serious Adverse Reaction (USAR) that is not pre-specified or is a known consequence of disease progression or complication of cirrhosis that:
Results in death
Is life-threatening
Required hospitalisation or prolongation of existing hospitalisation
Results in persistent or significant disability or incapacity
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End point type |
Primary
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End point timeframe |
Day 1 (endoscopy) to Day 90
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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: Please see attached report for analyses |
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No statistical analyses for this end point |
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End point title |
Assess tolerability of FMT e.g reflux rates [2] | |||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Administration to 2 hours
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Notes [2] - 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: Please see attached report for analyses |
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No statistical analyses for this end point |
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End point title |
Assess recruitment rates [3] | |||||||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Randomization to 90 days
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Notes [3] - 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: Please see attached report for analyses |
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No statistical analyses for this end point |
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End point title |
improvement in global liver synthetic function as assessed by the MELD score | |||||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Baseline to 90 days
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No statistical analyses for this end point |
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End point title |
Development of overt hepatic encephalopathy | |||||||||||||||
End point description |
The development of organ failure (hypotension requiring inotropic support, respiratory failure requiring ventilator support or the development of acute kidney injury requiring renal replacement therapy) and infection
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End point type |
Secondary
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End point timeframe |
Baseline to 90 days
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No statistical analyses for this end point |
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End point title |
The development of any infection | ||||||||||||||||||
End point description |
The development of any infection during the 90 day follow up including chest, urinary, stool, ascites and blood infection.
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End point type |
Secondary
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End point timeframe |
Baseline to 90 days
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No statistical analyses for this end point |
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End point title |
The development of organ failure | ||||||||||||
End point description |
The development of organ failure (hypotension requiring inotropic support, respiratory failure requiring ventilator support or the development of acute kidney injury requiring renal replacement therapy) and infection
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End point type |
Secondary
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End point timeframe |
Baseline to 90 days
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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 |
The period for AE reporting was from the date of the intervention up until 90 days post intervention.
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Assessment type |
Non-systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
23
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Reporting groups
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Reporting group title |
FMT- faecal microbiota transplantation
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Reporting group description |
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Reporting group title |
PLacebo
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Reporting group description |
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Frequency threshold for reporting non-serious adverse events: 0% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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31 Oct 2018 |
IMPD updated to change container |
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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. | |||
Mechanistic analyses are in progress and the manuscript is currently being drafted. |