Clinical Trial Results:
A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate a Potassium Normalization Treatment Regimen Including Sodium Zirconium Cyclosilicate (ENERGIZE)
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Summary
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EudraCT number |
2017-003955-50 |
Trial protocol |
DK IT |
Global end of trial date |
21 Dec 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
27 Dec 2019
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First version publication date |
27 Dec 2019
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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 |
D9480C00005
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03337477 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
AstraZeneca
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Sponsor organisation address |
One Medimmune Way, Gaithersburg, United States, MD 20878
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Public contact |
Study Information Center, AstraZeneca Clinical, +1 877 240 9479, information.center@astrazeneca.com
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Scientific contact |
Study Information Center, AstraZeneca Clinical, +1 877 240 9479, information.center@astrazeneca.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 |
25 Mar 2019
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
21 Dec 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
21 Dec 2018
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
The study is designed to determine if SZC 10g administered up to three times over 10h added to insulin and glucose in patients presenting with hyperkalaemia will prove tolerable and efficacious by performing a multicentre, international, randomized, double-blind, placebo-controlled, prospective, parallel-group study.
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Protection of trial subjects |
Study monitors will perform ongoing source data verification and source data review to confirm that the safety and rights of subjects are being protected.
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Background therapy |
insulin and glucose | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
13 Feb 2018
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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 |
Denmark: 2
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Country: Number of subjects enrolled |
Italy: 2
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Country: Number of subjects enrolled |
Russian Federation: 27
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Country: Number of subjects enrolled |
United States: 39
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Worldwide total number of subjects |
70
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EEA total number of subjects |
4
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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) |
46
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From 65 to 84 years |
22
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85 years and over |
2
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Recruitment
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Recruitment details |
Participants took part in the study in the United States, Russia, Denmark and Italy from 13 February 2018 to 21 December 2018. | ||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Patients with S-K ≥5.8 mmol/L for whom treatment with insulin and glucose to manage hyperkalaemia has been determined medically appropriate by the Investigator. The study originally recruited patients with S-K ≥6.0 mmol/L; however, this inclusion criterion was updated during CSP Amendment to allow enrolment of patients with S-K ≥5.8 mmol/L. | ||||||||||||||||||||||||
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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 |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||
Roles blinded |
Investigator, Monitor, Carer, Subject, Data analyst, Assessor | ||||||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Sodium Zirconium Cyclosilicate (SZC) 10g | ||||||||||||||||||||||||
Arm description |
SZC will be administered in addition to insulin and glucose. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Sodium Zirconium Cyclosilicate (SZC) 5g
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for oral suspension
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Routes of administration |
Oral use
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Dosage and administration details |
Powder for oral suspension in a sachet. Single dose contains two sachets that should be suspended in 45 mL of water by patient.
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Arm title
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Placebo | ||||||||||||||||||||||||
Arm description |
Placebo will be administered in addition to insulin and glucose. | ||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for oral suspension
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Routes of administration |
Oral use
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Dosage and administration details |
Powder for oral suspension in a sachet. Single dose contains two sachets that should be suspended in 45 mL of water by patient.
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Baseline characteristics reporting groups
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Reporting group title |
Sodium Zirconium Cyclosilicate (SZC) 10g
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Reporting group description |
SZC will be administered in addition to insulin and glucose. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Placebo will be administered in addition to insulin and glucose. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Sodium Zirconium Cyclosilicate (SZC) 10g
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Reporting group description |
SZC will be administered in addition to insulin and glucose. | ||
Reporting group title |
Placebo
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Reporting group description |
Placebo will be administered in addition to insulin and glucose. | ||
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End point title |
Mean absolute change in S-K from baseline until 4h after start of dosing with SZC/placebo | ||||||||||||
End point description |
The least squares means (LS-means) are derived from a linear regression model of absolute change in S-K at 4h with the following covariates: treatment group; baseline S-K; time from the start of dosing insulin to the start of dosing SZC/placebo and the dose (units/kg) of the first course of insulin. The 95% CI is associated with LS-Means.
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End point type |
Primary
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End point timeframe |
Baseline to 4h potassium measurements.
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Statistical analysis title |
Comparison with Placebo | ||||||||||||
Statistical analysis description |
Difference in LS-means
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Comparison groups |
Sodium Zirconium Cyclosilicate (SZC) 10g v Placebo
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Number of subjects included in analysis |
68
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
Method |
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Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-0.13
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Confidence interval |
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95% | ||||||||||||
sides |
2-sided
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lower limit |
-0.44 | ||||||||||||
upper limit |
0.17 | ||||||||||||
Variability estimate |
Standard deviation
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Dispersion value |
0.15
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End point title |
Fraction of patients responding to therapy defined as: S-K <6.0mmol/L between 1 and 4h and S-K <5.0mmol/L at 4h; and no additional potassium lowering therapy from 0 to 4h with exception of the initial insulin treatment | ||||||||||||
End point description |
Additional therapies for hyperkalaemia are 2nd dose of insulin, Beta-agonists, Diuretics, Dialysis, Sodium bicarbonate and Potassium binders when administered with the expressed intent to lower S-K. Patients with any missing potassium value from 1h to 4h inclusive will be treated as non-responders.
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End point type |
Secondary
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End point timeframe |
Baseline to 4h potassium meansurements.
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| No statistical analyses for this end point | |||||||||||||
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End point title |
The fraction of patients achieving normokalaemia 1, 2 and 4h after start of dosing with SZC/placebo | |||||||||||||||||||||
End point description |
Proportion of patients achieving normokalaemia, S-K 3.5-5.0 mmol/L, at 1, 2 and 4h after start of dosing
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End point type |
Secondary
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End point timeframe |
Baseline to 4h potassium meansurements.
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| No statistical analyses for this end point | ||||||||||||||||||||||
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End point title |
The fraction of patients achieving S-K <5.5mmol/l 1, 2, and 4h after start of dosing with SZC/placebo | |||||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Baseline to 4h potassium meansurements.
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| No statistical analyses for this end point | ||||||||||||||||||||||
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End point title |
The fraction of patients achieving S-K <6.0mmol/l 1, 2, and 4h after start of dosing with SZC/placebo | |||||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Baseline to 4h potassium meansurements.
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| No statistical analyses for this end point | ||||||||||||||||||||||
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End point title |
The fraction of patients administered additional potassium lowering therapy due to hyperkalaemia from 0 to 4h. | ||||||||||||
End point description |
Additional therapies for hyperkalaemia are 2nd dose of insulin, Beta-agonists, Diuretics, Dialysis, Sodium bicarbonate and Potassium binders when administered with the expressed intent to lower S-K.
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End point type |
Secondary
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End point timeframe |
Baseline to 4h potassium meansurements.
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Mean absolute change in S-K from baseline to 1h and 2h after start of dosing with SZC/placebo | ||||||||||||||||||
End point description |
The least squares means (LS-means) are derived from a linear regression model of absolute change in S-K at 1h and 2h with the following covariates: treatment group; baseline S-K; time from the start of dosing insulin to the start of dosing SZC/placebo and the dose (units/kg) of the first course of insulin. The 95% CI is associated with LS-Means.
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End point type |
Secondary
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End point timeframe |
Baseline to 2h potassium measurements.
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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 |
Adverse Events (including SAEs) were collected from time of signature of informed consent
form throughout the treatment period and including the follow-up period (Visit 2 or last contact).
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Adverse event reporting additional description |
AEs occurring between 0h to 24h and after 24h were summarised separately. AEs occurring between 0h to 24h are reported in EudraCT Results Form.
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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 |
21.1
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Reporting groups
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Reporting group title |
Sodium Zirconium Cyclosilicate (SZC) 10g
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Reporting group description |
SZC will be administered in addition to insulin and glucose. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Placebo will be administered in addition to insulin and glucose. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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13 Jun 2018 |
The primary purpose of the protocol amendment was to allow the study to integrate better with standard of care, while minimizing the impact on the scientific integrity of the study. |
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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. | |||
| Recruitment was stopped at 70 patients randomized instead of 132, as initially planned. | |||
