Download PDF

Clinical Trial Results:
Impact of Daflon 500 mg on the progression of chronic venous disease and symptoms in patients operated on for varicose veins with conservation of the great saphenous vein. A multicentre, double blind randomised, placebo controlled, parallel group study.

Summary
EudraCT number	2010-021270-11
Trial protocol	FR
Global end of trial date	30 Jun 2014

Results information
Results version number	v1(current)
This version publication date	06 Jul 2016
First version publication date	31 Jul 2015
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

CL2-05682-102

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

Institut de Recherches Internationales Servier (I.R.I.S)

Sponsor organisation address

50 rue Carnot, Suresnes Cedex, France, 92284

Public contact

ITP(Innovation Therapeutic Pole), Institut de Recherches Internationales Servier (I.R.I.S), +33 155724366, clinicaltrials@servier.com

Scientific contact

ITP(Innovation Therapeutic Pole), Institut de Recherches Internationales Servier (I.R.I.S), +33 155724366, clinicaltrials@servier.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

30 Jun 2014

Is this the analysis of the primary completion data?

Yes

Primary completion date

30 Jun 2014

Global end of trial reached?

Yes

Global end of trial date

30 Jun 2014

Was the trial ended prematurely?

Yes

Main objective of the trial

To evaluate the effect of Daflon®500 mg (1000 mg per day) on the progression of chronic venous disease and symptoms after surgical treatment of varicose veins by phlebectomy with conservation of the great saphenous vein (ASVAL method).

Protection of trial subjects

The reason for premature discontinuation of the study could be: - Adverse events or any condition incompatible with continuation of either treatment according to the investigator, - Major deviation from the protocol (unauthorized concomitant treatment, pregnancy or event that could endanger the patient’s safety…), - Decision by the subject to withdraw from the study, - Non-medical reason, In case of premature discontinuation of treatment the patient will be withdrawn from the study. When the investigator has no news of the participant, he must make every effort to contact him/her, to establish the reason for the discontinuation of treatment, and to suggest the participant comes to an end-of-study visit. If all these attempts to contact the participant fail, the investigator can then declare the participant “lost to follow-up”. The investigator should document all these attempts in the corresponding medical file.

Background therapy

Evidence for comparator

Actual start date of recruitment

29 Apr 2011

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

France: 119

Worldwide total number of subjects

119

EEA total number of subjects

119

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Screening details

Demographic characteristics : -Male or female, -Outpatient, -Aged between 18 and 85 years (inclusive), -For French patient, beneficiary or registered with the French social safety or the social security of Monaco (supressed according to the amendment No. 2).

Period 1 title

Overall study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Data analyst, Carer

Are arms mutually exclusive

Yes

Daflon

Arm description

Arm type

Experimental

Investigational medicinal product name

Daflon 500 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

The dosage was two tablets daily (at lunchtime) from the day after ASVAL surgery (D1) to M6. The day of surgery (D0), the investigator reminded the patient of beginning the treatment intake the day after (D1). If the patient forgot to take his treatment at lunchtime, it was recommended to take it as soon as he realized his omission during the same day.

Placebo

Arm description

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Number of subjects in period 1	Daflon	Placebo
Started	59	60
Completed	22	24
Not completed	37	36
Adverse event, non-fatal	2	1
Non-medical reason	32	34
Protocol deviation	3	1

Baseline characteristics

Top of page

Reporting group title

Overall study

Reporting group description

Reporting group values	Overall study	Total
Number of subjects	119	119
Age categorical
Units: Subjects
In utero	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0
Newborns (0-27 days)	0	0
Infants and toddlers (28 days-23 months)	0	0
Children (2-11 years)	0	0
Adolescents (12-17 years)	0	0
Adults (18-64 years)	90	90
From 65-84 years	28	28
85 years and over	1	1
Gender categorical
Units: Subjects
Female	91	91
Male	28	28

End points

Top of page

Reporting group title

Daflon

Reporting group description

Reporting group title

Placebo

Reporting group description

Primary: Saphenous reflux volume

Top of page

End point title

Saphenous reflux volume

End point description

Volume (mm³) of the reflux of the great saphenous vein : Change from baseline to M3 during the study and between-group comparison - On the most affected leg - FAS (N = 72).

End point type

Primary

End point timeframe

From Baseline to M3

End point values	Daflon	Placebo
Number of subjects analysed	31	41
Units: mm³
arithmetic mean (standard deviation)	-4478.71 ± 4714.756	-3766.22 ± 3953.772

Between group difference estimate using an ANCOVA

Statistical analysis description

Parametric approach with adjustement

Comparison groups

Daflon v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

-121.976

Confidence interval

level

95%

sides

2-sided

lower limit

-891.77

upper limit

647.818

Variability estimate

Standard error of the mean

Dispersion value

385.771

Adverse events

Top of page

Timeframe for reporting adverse events

Overall study

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

17.0

Reporting group title

Daflon

Reporting group description

Reporting group title

Placebo

Reporting group description

Serious adverse events	Daflon	Placebo
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 46 (2.17%)	1 / 52 (1.92%)
number of deaths (all causes)	0	0
number of deaths resulting from adverse events	0	0
Injury, poisoning and procedural complications
Joint dislocation
subjects affected / exposed	1 / 46 (2.17%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac disorders
Acute myocardial infarction
subjects affected / exposed	0 / 46 (0.00%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 1%

Non-serious adverse events	Daflon	Placebo
Total subjects affected by non serious adverse events
subjects affected / exposed	10 / 46 (21.74%)	6 / 52 (11.54%)
Injury, poisoning and procedural complications
Joint dislocation
subjects affected / exposed	1 / 46 (2.17%)	0 / 52 (0.00%)
occurrences all number	1	0
Post procedural contusion
subjects affected / exposed	1 / 46 (2.17%)	0 / 52 (0.00%)
occurrences all number	1	0
Vascular disorders
Venous insufficiency
subjects affected / exposed	3 / 46 (6.52%)	4 / 52 (7.69%)
occurrences all number	3	5
Thrombophlebitis superficial
subjects affected / exposed	1 / 46 (2.17%)	0 / 52 (0.00%)
occurrences all number	1	0
Varicose vein
subjects affected / exposed	1 / 46 (2.17%)	0 / 52 (0.00%)
occurrences all number	1	0
Cardiac disorders
Atrial flutter
subjects affected / exposed	0 / 46 (0.00%)	1 / 52 (1.92%)
occurrences all number	0	1
Acute myocardial infarction
subjects affected / exposed	0 / 46 (0.00%)	1 / 52 (1.92%)
occurrences all number	0	1
Nervous system disorders
Migraine
subjects affected / exposed	0 / 46 (0.00%)	1 / 52 (1.92%)
occurrences all number	0	1
General disorders and administration site conditions
Injection site reaction
subjects affected / exposed	1 / 46 (2.17%)	0 / 52 (0.00%)
occurrences all number	1	0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	0 / 46 (0.00%)	1 / 52 (1.92%)
occurrences all number	0	1
Nausea
subjects affected / exposed	1 / 46 (2.17%)	0 / 52 (0.00%)
occurrences all number	1	0
Skin and subcutaneous tissue disorders
Pruritus allergic
subjects affected / exposed	1 / 46 (2.17%)	0 / 52 (0.00%)
occurrences all number	1	0
Musculoskeletal and connective tissue disorders
Osteoarthritis
subjects affected / exposed	1 / 46 (2.17%)	0 / 52 (0.00%)
occurrences all number	1	0
Infections and infestations
Diverticulitis
subjects affected / exposed	0 / 46 (0.00%)	1 / 52 (1.92%)
occurrences all number	0	1
Metabolism and nutrition disorders
Type 2 diabetes mellitus
subjects affected / exposed	0 / 46 (0.00%)	1 / 52 (1.92%)
occurrences all number	0	1

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

14 Oct 2010

This amendment has been implemented to clarify inclusion criteria with a pregnancy test added, to clarify the main and secondary criteria and to update the statistical method

20 Jul 2011

This amendment has been implemented: - To modify the beginning of the recruitment. Indeed the initiation date was delayed from December 2010 to April 2011 due to technical problems. - To extend the recruitment period by one year. The observed recruitment rate is only one half of that expected when the study was planned. This is mainly due to the loss of one centre (Monaco), which represents 36 % of the recruitment and to selection criteria. The study completion date is April 2014. - Therefore two modifications are proposed: �� The modification of the selection criteria regarding phleboactive drugs. The planned period of 3 months without any phleboactive drugs preceding surgery has been changed to one month before the selection of the patient without any impact on the primary criterion. �� The modification of the duration between the selection (SEL) and inclusion (INCL) visits which were initially planned at D-45 (for SEL) and D-15 to D-1 (for INCL) before surgery. In clinical practice, patients could request to be operated promptly. Therefore, for more flexibility, the duration between the selection and inclusion visits will be between 0 and 90 days with a selection visit scheduled maximum at D-90 and an inclusion visit scheduled at least at D-1 before surgery. The selection / inclusion visits could be realized at the same time. - To modify the number of centres due to the non-participation of Monaco.

23 Oct 2012

This amendment has been implemented: - To extend the recruitment period by 18 months. The observed recruitment rate is less than one half of that expected when the study was planned (70 included patients instead of 170 at the end of September 2012). This is mainly due to the loss of one centre (Monaco), which represented 36% of the recruitment and to selection criteria. The study completion date is October 2015.

Were there any global interruptions to the trial? Yes

Date	Interruption	Restart date
30 Jun 2014	Due to strategic decision, the study has been prematurely terminated with only 119 included patients (instead of 300 patients planned): consequently, only the primary efficacy endpoint (volume of the reflux in the Great Saphenous vein (GSV) was analysed.	-

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

The section NSAE presented EAEs on treatment and included SEAEs. The causality and seriousness of reported SAE can be ultimately upgraded by the sponsor. The sponsor took the decisions to be compliant with exiting ICH E3 Clinical Study Report.

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Clinical trials

Clinical Trial Results:
Impact of Daflon 500 mg on the progression of chronic venous disease and symptoms in patients operated on for varicose veins with conservation of the great saphenous vein. A multicentre, double blind randomised, placebo controlled, parallel group study.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Saphenous reflux volume

Primary: Saphenous reflux volume

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: Impact of Daflon 500 mg on the progression of chronic venous disease and symptoms in patients operated on for varicose veins with conservation of the great saphenous vein. A multicentre, double blind randomised, placebo controlled, parallel group study.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Saphenous reflux volume

Primary: Saphenous reflux volume

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
Impact of Daflon 500 mg on the progression of chronic venous disease and symptoms in patients operated on for varicose veins with conservation of the great saphenous vein. A multicentre, double blind randomised, placebo controlled, parallel group study.