Clinical Trial Results:
Effects on Exercise Hemodynamics of Vasopressin Blockade by Conivaptan Infusion in Heart Failure
Summary
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EudraCT number |
2012-003219-77 |
Trial protocol |
DK |
Global end of trial date |
26 Jun 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
25 Nov 2021
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First version publication date |
25 Nov 2021
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Other versions |
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 |
2012-003219-77
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01752543 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
The Heart Centre, Copenhagen University Hospital, Rigsohospitalet
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Sponsor organisation address |
Blegdamsvej 9, Copenhagen, Denmark, 2100
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Public contact |
Finn Gustafsson, Copenhagen University Hospital, Rigshospitalet, 0045 35459743, Finn.Gustafsson@regionh.dk
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Scientific contact |
Finn Gustafsson, Copenhagen University Hospital, Rigshospitalet, 0045 35459743, Finn.Gustafsson@regionh.dk
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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 |
20 May 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
20 May 2015
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Global end of trial reached? |
Yes
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Global end of trial date |
26 Jun 2016
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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 test if infusion of the V1A/V2-receptor blocker conivaptan improves hemodynamics and physical capacity in HF patients on optimal HF medical therapy and to improve understanding of the role of vasopressin in HF.
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Protection of trial subjects |
The study was performed according to the Helsinki Declaration and data was anonymized and t
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Nov 2012
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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: 20
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Worldwide total number of subjects |
20
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EEA total number of subjects |
20
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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) |
13
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From 65 to 84 years |
7
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85 years and over |
0
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Recruitment
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Recruitment details |
Patients were included from 13. December 2013 to 20. May 2015 All patients were followed in the outpatient clinic at the University Hopsital of Copenhagen, Rigshospitalet, Denmark | |||||||||
Pre-assignment
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Screening details |
Patients (> 18 years old) with left ventricular systolic dysfunction evaluated by an ejection fraction < 45 % and with symptomatic HF (NYHA-class II-IV) were eligible for enrollment in the present study. All patients were followed in the outpatient HF clinic at the University Hospital of Copenhagen (Rigshospitalet). | |||||||||
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 |
Investigator, Monitor, Data analyst, Carer, Subject, Assessor | |||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Conivaptan group | |||||||||
Arm description |
Patients who received conivaptan | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
Conivaptan
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection/infusion
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Routes of administration |
Infusion
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Dosage and administration details |
Patients received a 20 mg loading dose followed by a continuous infusion of conivaptan of 0.83
mg/h as recommended in conivaptan treatment guidelines.
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Arm title
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Placebo group | |||||||||
Arm description |
Patients who received placebo | |||||||||
Arm type |
Placebo | |||||||||
Investigational medicinal product name |
saline
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Infusion
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Dosage and administration details |
Patients received a loading noise of 100 ml/30 min followed by an infusion og 4.2 ml/hours corresponding to the infusion rate of the patients in the conivaptan group
Conivaptan/saline was administered by a study nurse
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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 |
Conivaptan group
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Reporting group description |
Patients who received conivaptan | ||
Reporting group title |
Placebo group
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Reporting group description |
Patients who received placebo |
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End point title |
to investigate if treatment with conivaptan leads to a decrease in pulmonary capillary wedge pressure (PCWP) and/or an increase in cardiac output during submaximal exercise (defined as 50 % of the submaximal exercise capacity) compared with placebo. | |||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Patients were included from 13. December 2013 to 20. May 2015
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Statistical analysis title |
Statistical analyses | |||||||||
Statistical analysis description |
Within group differences were tested using the paired t-test.
Between group differences were tested using two-sided t-test and a general linear ANCOVA model
with treatment as a fixed effect and baseline value as a covariate
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Comparison groups |
Conivaptan group v Placebo group
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Number of subjects included in analysis |
20
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Analysis specification |
Pre-specified
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Analysis type |
other | |||||||||
P-value |
> 0.05 | |||||||||
Method |
ANCOVA | |||||||||
Confidence interval |
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Adverse events information [1]
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Timeframe for reporting adverse events |
Follow-up information regarding hospitalization, death, heart
transplantation or implantation of a left ventricular assist device was collected after 60, 90 and 365
days for all patients included in the study
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Assessment type |
Systematic | ||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||
Dictionary version |
18.0
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Reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
- | ||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||
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Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: There were no adverse events during infusion of conivaptan or placebo or at the 1- week or one-month follow-up in either group. Infusion of conivaptan was not associated with electrolyte disturbances, important changes of vital parameters or cardiac arrhythmias. There were no infusion site reactions in the conivaptan or the placebo group. One patient in the conivaptan group and and one patient in the placebo group died from worsening HF before the 6 month follow-up visit. |
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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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14 Jan 2015 |
We applied for an amendment to prolongate the inclusion period as were we behind schedule with the inclusion of patients |
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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 |