Clinical Trial Results:
Serelaxin To Lower Portal Pressure in Patients with Cirrhosis and Portal Hypertension (STOPP)
Summary
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EudraCT number |
2015-004031-12 |
Trial protocol |
GB |
Global end of trial date |
31 Aug 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
26 Jan 2020
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First version publication date |
26 Jan 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 |
AC15007
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02669875 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
ACCORD (Academic and Clinical Central Office for Research and Development for NHS Lothian/University of Edinburgh)
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Sponsor organisation address |
Queen's Medical Research Institute, Edinburgh BioQuarter, 47 Little France Crescent, Edinburgh, United Kingdom, EH16 4TJ
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Public contact |
Professor Jonathan Fallowfield, University of Edinburgh, 44 01312426589, Jonathan.Fallowfield@ed.ac.uk
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Scientific contact |
Professor Jonathan Fallowfield, University of Edinburgh, 44 01312426589, Jonathan.Fallowfield@ed.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 |
31 Aug 2019
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
31 Aug 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Aug 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 |
To demonstrate that 2 hours treatment with serelaxin through a drip reduces the portal pressure in patients with liver cirrhosis and high blood pressure in the portal vein.
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Protection of trial subjects |
We offered participants the option of a small dose of sedative (midazolam) prior to insertion of the femoral venous catheter.
Fluoroscopic (x-ray) screening was kept to an absolute minimum (catheter positioning only).
We used a non-invasive method to measure cardiac output so did not need to pass a catheter into the heart, thus obviating the risk of cardiac arrhythmias associated with right atrial pressure measurement.
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Background therapy |
- | ||
Evidence for comparator |
The small placebo control arm was included to allow double-blindness (not as a comparison group) and to help generate valuable information for designing a future larger randomised controlled trial. | ||
Actual start date of recruitment |
19 Oct 2017
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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 |
United Kingdom: 15
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Worldwide total number of subjects |
15
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EEA total number of subjects |
15
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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 |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
This was a single-site study, undertaken at the Royal Infirmary of Edinburgh (Edinburgh, UK) between 19th October 2017 and 31st August 2018. | ||||||||||||
Pre-assignment
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Screening details |
A total of 17 participants were screened. Of these, 2 had a screening failure and did not proceed to randomisation. Fifteen patients were randomised and 11 completed the trial (n=9 serelaxin, n=2 placebo). Reasons for withdrawal were baseline HVPG <10 mmHg (n=2) and technical failure (n=2). | ||||||||||||
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 |
Double blind | ||||||||||||
Roles blinded |
Subject, Investigator | ||||||||||||
Blinding implementation details |
Both treatments were prepared to be similar in appearance, colour, and organoleptic properties.
The procedures for emergency unblinding complied with the European Clinical Trials Directive 2001/20/EC (EUCTD).
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Arms
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Arm title
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Serelaxin | ||||||||||||
Arm description |
Recombinant human relaxin-2 (serelaxin (Novartis Pharmaceuticals, UK)) administered via peripheral i.v. infusion. | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Serelaxin
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Investigational medicinal product code |
RLX030
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Other name |
recombinant human relaxin-2
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Pharmaceutical forms |
Concentrate for solution for injection/infusion
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Routes of administration |
Intravenous drip use
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Dosage and administration details |
80 μg/kg/day for 60 min followed by 30 μg/kg/day for at least 60 min. This was achieved by a single infusion bag with a change in the administration rate.
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Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: The primary outcome relates to the change at 2 hours in the treated group; the placebo group was included only to help maintain the blind (investigators could not be confident that a treatment had been received) and to provide a background rate of adverse events |
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Baseline characteristics reporting groups
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Reporting group title |
Serelaxin
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Reporting group description |
Recombinant human relaxin-2 (serelaxin (Novartis Pharmaceuticals, UK)) administered via peripheral i.v. infusion. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Serelaxin
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Reporting group description |
Recombinant human relaxin-2 (serelaxin (Novartis Pharmaceuticals, UK)) administered via peripheral i.v. infusion. | ||
Subject analysis set title |
Baseline HVPG
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
The primary endpoint was the change from baseline in fasting hepatic venous pressure gradient (HVPG) after 2 hr serelaxin infusion. No formal comparison will be made between treatment and placebo.
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Subject analysis set title |
2h HVPG following serelaxin
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
value at 2 hours
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End point title |
HVPG | ||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
The primary outcome is to examine if the baseline to 2 hr change in fasting hepatic venous pressure gradient (HVPG) is a clinically significant one.
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Attachments |
Untitled (Filename: Figure2HVPG.pdf) |
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Notes [1] - data for end of trial reported here |
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Statistical analysis title |
paired t-test | ||||||||||||||||
Comparison groups |
Baseline HVPG v 2h HVPG following serelaxin
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Number of subjects included in analysis |
18
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.76 | ||||||||||||||||
Method |
t-test, 2-sided | ||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||
Point estimate |
0.4
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Confidence interval |
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level |
95% | ||||||||||||||||
sides |
2-sided
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lower limit |
-2.3 | ||||||||||||||||
upper limit |
3.1 | ||||||||||||||||
Variability estimate |
Standard deviation
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Dispersion value |
3.5
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Adverse events information
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Timeframe for reporting adverse events |
Overall trial
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Adverse event reporting additional description |
Safety assessments included collection of adverse events (AE), clinical examination, vital signs, laboratory tests and electrocardiograms (ECGs). Both the severity of AEs and relation to study medication treatment was collected.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20.0
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Reporting groups
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Reporting group title |
Serelaxin
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Reporting group description |
Recombinant human relaxin-2 (serelaxin (Novartis Pharmaceuticals, UK)) administered via peripheral i.v. infusion. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Placebo for serelaxin | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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04 Oct 2016 |
The amendment related to a protocol update. The PIS and consent were updated in-line with the changes. There was also the addition of new documents (Female Partner Information Sheet and Consent plus the GP letter). |
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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. | |||
The study was terminated before the recruitment target was met due to a global drug supply issue (Novartis stopped manufacturing serelaxin and there was none available with a shelf-life beyond 31st August 2018). Therefore, the study was underpowered. |