Clinical Trial Results:
The Efficacy and Safety of Valsartan and Combination of Valsartan and Hydrochlorothiazide in the Treatment of Patients with mild to moderate Arterial Hypertension.
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Summary
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EudraCT number |
2012-005129-57 |
Trial protocol |
SI CZ |
Global end of trial date |
23 Jun 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
07 Jun 2020
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First version publication date |
07 Jun 2020
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Other versions |
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Summary report(s) |
VICTORY_Final_Report_Synopsis |
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 |
KCT02/2012-VICTORY
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Krka, d.d., Novo mesto
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Sponsor organisation address |
Dunajska 65, Ljubljana, Slovenia, 1000
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Public contact |
Tanja Kohek, Krka, d.d., Novo mesto
Dunajska 65
1000 Ljubljana, 00386 14751236, tanja.kohek@krka.biz
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Scientific contact |
Tanja Kohek, Krka, d.d., Novo mesto
Dunajska 65
1000 Ljubljana, 00386 14751236, tanja.kohek@krka.biz
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Sponsor organisation name |
Krka ČR, s.r.o.
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Sponsor organisation address |
Sokolovská 192/79, Prague, Czech Republic, 180 00
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Public contact |
Martin Sustr, Krka ČR, s.r.o.,
Sokolovská 192/79
180 00 Prague, 00420 602 486846, martin.sustr@krka.biz
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Scientific contact |
Martin Sustr, Krka ČR, s.r.o.,
Sokolovská 192/79
180 00 Prague, 00420 602 486846, martin.sustr@krka.biz
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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 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
23 Jun 2015
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Global end of trial reached? |
Yes
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Global end of trial date |
23 Jun 2015
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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 aim of the study was to establish the efficacy and safety of Valsacor® (valsartan) and Valsacombi® (combination of valsartan and hydrochlorothiazide) in wide populations of patients with mild to moderate arterial hypertension.
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Protection of trial subjects |
Previously treated patients had 1 week wash-out period before the active treatment started. All patients who met inclusion criteria of the trial were prescribed 1 tablet of Valsacor® 80 mg daily (only in Russia previously treated patients received Valsacor® 160 mg). The dose was adjusted on V2 (4 weeks), V3 (8 weeks) and V4 (12 weeks) according to achievement of target BP.
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Background therapy |
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Evidence for comparator |
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Actual start date of recruitment |
20 May 2013
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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 |
Russian Federation: 130
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Country: Number of subjects enrolled |
Croatia: 68
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Country: Number of subjects enrolled |
Czech Republic: 58
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Country: Number of subjects enrolled |
Ukraine: 102
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Country: Number of subjects enrolled |
Slovenia: 7
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Worldwide total number of subjects |
365
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EEA total number of subjects |
133
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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) |
291
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From 65 to 84 years |
74
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85 years and over |
0
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Recruitment
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Recruitment details |
There were 365 patients recruited from 5 countries: Russia, Croatia, Czech Republic, Ukraine and Slovenia. | ||||||||||||||||||
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Pre-assignment
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Screening details |
Patients older than 18 years of both genders with mild to moderate essential hypertension with SBP of 140 – 179 mm Hg and DBP of 90 – 109 mm Hg, who signed informed consent form were eligible for inclusion 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 |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||
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Arms
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Arm title
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All Patients | ||||||||||||||||||
Arm description |
All patients that were enrolled in the study. The treatment was initiated with 1 tablet of Valsacor® 80 mg daily in all patients (naïve and previously treated patients with 1 week washout period). After four weeks of treatment (V2), the dose was adjusted to 1 tablet of Valsacor® 160 mg daily in patients whose target BP was not achieved. After consequent 4 weeks (V3) in insufficiently treated patients the dose was increased to either Valsacor® 320 mg or Valsacombi® 160/12.5 mg. If target BP levels were not achieved after additional 4 weeks (V4) the dose was increased to Valsacombi® 320/12.5 mg. If the target BP was achieved, the treatment remained the same for another 4 weeks. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Valsacor® 80 mg
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
1 tablet daily. One tablet contains 80 mg of valsartan.
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Investigational medicinal product name |
Valsacor® 160 mg
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
1 tablet daily. One tablet contains 160 mg of valsartan.
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Investigational medicinal product name |
Valsacor® 320 mg
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
1 tablet daily. One tablet contains 320 mg of valsartan.
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Investigational medicinal product name |
Valsacombi® 160/12.5 mg
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
1 tablet daily. One tablet contains 160 mg of valsartan and 12.5 mg of hydrochlorothiazide.
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Investigational medicinal product name |
Valsacombi® 320/12.5 mg
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
1 tablet daily. One tablet contains 320 mg of valsartan and 12.5 mg of hydrochlorothiazide.
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Baseline characteristics reporting groups
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Reporting group title |
All Patients
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Reporting group description |
All patients that were enrolled in the study. The treatment was initiated with 1 tablet of Valsacor® 80 mg daily in all patients (naïve and previously treated patients with 1 week washout period). After four weeks of treatment (V2), the dose was adjusted to 1 tablet of Valsacor® 160 mg daily in patients whose target BP was not achieved. After consequent 4 weeks (V3) in insufficiently treated patients the dose was increased to either Valsacor® 320 mg or Valsacombi® 160/12.5 mg. If target BP levels were not achieved after additional 4 weeks (V4) the dose was increased to Valsacombi® 320/12.5 mg. If the target BP was achieved, the treatment remained the same for another 4 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
All Patients
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Reporting group description |
All patients that were enrolled in the study. The treatment was initiated with 1 tablet of Valsacor® 80 mg daily in all patients (naïve and previously treated patients with 1 week washout period). After four weeks of treatment (V2), the dose was adjusted to 1 tablet of Valsacor® 160 mg daily in patients whose target BP was not achieved. After consequent 4 weeks (V3) in insufficiently treated patients the dose was increased to either Valsacor® 320 mg or Valsacombi® 160/12.5 mg. If target BP levels were not achieved after additional 4 weeks (V4) the dose was increased to Valsacombi® 320/12.5 mg. If the target BP was achieved, the treatment remained the same for another 4 weeks. | ||
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End point title |
Antihypertensive efficacy of Valsacor® and Valsacombi® [1] | ||||||||||||||||||||||||||||
End point description |
The primary efficacy endpoint was to evaluate the effect of Valsacor® and Valsacombi® on BP reduction and achievement of target BP. At each control visit, the BP was measured and according to results, the achievement of target BP was obtained.
During the trial, the mean values of SBP and DBP were steadily decreasing. The mean absolute decrease of SBP and DBP were 26.60 ± 10.41 mm Hg and 14.84 ± 7.57 mm Hg, respectively. On the other hand, the mean relative decrease of both SBP and DBP were 16.8 ± 6.1% and 15.2 ± 7.3%, respectively. The decrease of mean SBP and DBP was statistically significant (p < 0.0001) between all of the consecutive visits.
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End point type |
Primary
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End point timeframe |
16 weeks for one patient - was the same for the whole duration of the study (20.5.2013 - 23.6.2015).
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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: Statistical analysis could not be entered because the interface insisted on selecting at least two arms. The data was statistically processed: the largest and the smallest data, arithmetic mean of data with standard deviation of data and standard error of mean and the value of t variable in t-test. The unpaired two-tailed Student’s t-test and 95% confidence interval was used to compare values between the treatment groups. Differences were considered to be significant at p < 0.05. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||
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End point title |
Effect of treatment on aortic stiffness [2] | ||||||||||||
End point description |
The effect of treatment on aortic stiffness was evaluated indirectly based on the results of PWV (Pulse wave velocity).
The results on the first and the last visit show that mean PWV value at the beginning of the trial was significantly higher than the mean PWV value at the end of the trial. This means that the change of artery diameter at the beginning of the trial was lower than at the end of the trial, proving that aortic stiffness was higher at the beginning of the trial.
The mean absolute decrease of PWV from the first to the last visit was 0.95 ± 1.87 m/s and mean relative decrease of PWV was 8.4 ± 17.6 %. The decrease of PWV during the trial was statistically significant (p < 0.0001).
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End point type |
Primary
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End point timeframe |
16 weeks for one patient - was the same for the whole duration of the study (20.5.2013 - 23.6.2015).
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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: Statistical analysis could not be entered because the interface insisted on selecting at least two arms. The data was statistically processed: the largest and the smallest data, arithmetic mean of data with standard deviation of data and standard error of mean and the value of t variable in t-test. The unpaired two-tailed Student’s t-test and 95% confidence interval was used to compare values between the treatment groups. Differences were considered to be significant at p < 0.05. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Effects of treatment on aortic augmentation index (Alx) [3] | ||||||||||||
End point description |
The mean Alx values on the first and the last visit of the trial. The mean absolute decrease of Alx from the first to the last visit was 0.23 ± 10.78. The decrease was not statistically significant (p = 0.855).
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End point type |
Primary
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End point timeframe |
16 weeks for one patient - was the same for the whole duration of the study (20.5.2013 - 23.6.2015).
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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: Statistical analysis could not be entered because the interface insisted on selecting at least two arms. The data was statistically processed: the largest and the smallest data, arithmetic mean of data with standard deviation of data and standard error of mean and the value of t variable in t-test. The unpaired two-tailed Student’s t-test and 95% confidence interval was used to compare values between the treatment groups. Differences were considered to be significant at p < 0.05. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Central and peripheral BP reduction from V1 to V5 [4] | ||||||||||||||||||||||||
End point description |
The data on central and peripheral BP were obtained on the first and the last visit of the trial in 74 patients.
The mean absolute decrease of central SBP and DBP were 19.69 ± 12.95 mm Hg (mean relative decrease was 13.8 ± 8.6%) and 13.99 ± 8.51 mm Hg (mean relative decrease was 14.3 ± 8.5%), respectively. On the other hand, the mean absolute decrease of peripheral SBP and DBP were 20.93 ± 12.79 mm Hg (mean relative decrease was 13.6 ± 7.7%) and 13.84 ± 8.69 mm Hg (mean relative decrease was 14.3 ± 8.8%), respectively.
The decrease of both central and peripheral mean SBP and DBP between the first and the last visit of the trial were statistically significant (p < 0.0001).
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End point type |
Primary
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End point timeframe |
16 weeks for one patient - was the same for the whole duration of the study (20.5.2013 - 23.6.2015).
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| Notes [4] - 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: Statistical analysis could not be entered because the interface insisted on selecting at least two arms. The data was statistically processed: the largest and the smallest data, arithmetic mean of data with standard deviation of data and standard error of mean and the value of t variable in t-test. The unpaired two-tailed Student’s t-test and 95% confidence interval was used to compare values between the treatment groups. Differences were considered to be significant at p < 0.05. |
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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 |
16 weeks for one patient - was the same for the whole duration of the study (20.5.2013 - 23.6.2015).
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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 |
18.0
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Reporting groups
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Reporting group title |
All Patients
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 1% | |||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
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 | |||
