TRICOLOR: The Use of TrIple Fixed-dose Combination in the Treatment of Arterial Hypertension

• Sponsor: Servier Russia (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03722524
• Collaborator: (none)
• Enrollment: 1,247
• Locations: 51
• Actual Duration (Months): 9.5
• Patients Per Site: 24.5
• Patients Per Site Per Month: 2.6

Study Details

Study Description

Brief Summary

The use of TRIple fixed-dose COmbination in the treatment of arteriaL hypertension:

opportunity for effective BP control with cOmbined antihypertensive therapy.

The main aim of this study to assess the antihypertensive effectiveness effect on the 24-hour BP profile, as well as tolerability of and compliance to the treatment with a triple FDC of amlodipine / indapamide / perindopril arginine in hypertensive patients in the real clinical practice.

Type of program: Multicenter, observational, non-controlled, open-label program.

Investigators: Cardiologists and outpatient (primary care) physicians (general practitioners).

Number of patients: 1,300 hypertensive patients.

Condition or Disease	Intervention/Treatment	Phase
Arterial Hypertension	Drug: amlodipine / indapamide / perindopril arginine FDC

Detailed Description

It is multicenter, observational, non-controlled, open-label program. The baseline characteristics will be analyzed in all the patients who started the treatment (intention-to-treat [ITT] population). In case of significant differences between two treatment groups, the baseline characteristics will be provided for both of them.

Changes in the SBP and DBP (with the corresponding confidence intervals) will be assessed in the patients who completed the program without major deviations from protocol (per-protocol population [PPP]).

The analysis of parameters with normal distribution will be performed using the Student's t-test for paired measurements; otherwise the non-parametric Wilcoxon test will be used. The percentage of patients with normalized BP, as well as the percentage of patients who responded to treatment (with 95% confidence intervals), will be calculated.

Questionnaires: The score for each scale will be calculated as the sum of scores for questions constituting the scale.

Assessment of the AEs will be carried out in all the patients who started the treatment (ITT population).

Study Design

• Study Type: Observational
• Actual Enrollment: 1247 participants
• Observational Model: Other
• Time Perspective: Prospective
• Official Title: Multinational Observational Uncontrolled Open Programme "The Use of TRIple Fixed-dose COmbination in the Treatment of arteriaL Hypertension: Opportunity for Effective BP Control With cOmbined Antihypertensive Therapy"
• Actual Study Start Date: Oct 1, 2018
• Actual Primary Completion Date: Jul 17, 2019
• Actual Study Completion Date: Jul 17, 2019

Arms and Interventions

Arm

Intervention/Treatment

Patients with arterial hypertension The patient is included in the program if prior to the study his/her doctor decided to adjust treatment, targeted at the BP control improvement, by prescription of a triple FDC of amlodipine / indapamide / perindopril arginine. The prescription of the triple FDC of amlodipine / indapamide / perindopril arginine during the program is made by the doctor's decision according to the instructions for medical use of this FDC. Presumably, each doctor will include 4 patients in average. It is planned to include 1,300 patients.

Drug: amlodipine / indapamide / perindopril arginine FDC; CCB / diuretic / ACE inhibitor; Other Names: CCB / diuretic / ACE inhibitor

Outcome Measures

Primary Outcome Measures

1. The Mean Systolic BP Changes (mm Hg) at the Visit 4 vs. Baseline [Baseline, 3 months]

   Changes in the mean office systolic BP levels (in mm Hg) in the sitting position Blood pressure was measured in accordance with the guidelines of the European Society of Hypertension (ESH) using the auscultatory or oscillometric method and a semi-automated sphygmomanometer. Before taking measurements, the patient remained in a sitting position for 3-5 minutes. Blood pressure was determined on each arm, and the arm with the highest value was taken as the reference. Measurements were taken thrice in the sitting position of a patient, and the average of the second and third BP measurements on the reference arm with an interval of at least 1-2 minutes was recorded.

2. The Mean Diastolic BP Changes (mm Hg) at the Visit 4 vs Baseline. [Baseline, 3 months]

   Changes in the mean office diastolic BP levels (in mm Hg) in the sitting position

Secondary Outcome Measures

1. Percentage of Patients Who Achieved the Target Office BP Levels (SBP <140 mm Hg and DBP <90 mm Hg) at Visit 4 vs Baseline [Baseline, 3 months]

   The assessment of the target office BP levels (SBP <140 mm Hg and DBP <90 mm Hg) was performed in accordance with ESC Guidelines for the management of arterial hypertension (2013)

2. The Mean Standardized Score of the Physical Component of the Quality of Life Questionnaire The Short Form (36) Health Survey at Visit 4 vs Baseline [Baseline, 3 months]

   Change in the mean score of the of the physical component of the The Short Form (36) Health Survey (SF-36) survey. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.

3. The Mean Standardized Score of the Mental Component of the Quality of Life Questionnaire The Short Form (36) Health Survey at Visit 4 vs Baseline [Baseline, 3 months]

   Change in the mean score of the of the physical component of the SF-36 survey Change in the mean score of the of the physical component of the The Short Form (36) Health Survey (SF-36) survey. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 79 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age 18 to 79 years

• Essential hypertension

• Patient's consent to participate in the program

• Doctor's decision to prescribe FDC of amlodipine / indapamide / perindopril arginine, according to the instruction for use, prior to the inclusion in the program.

Exclusion Criteria:

• Symptomatic, or secondary arterial hypertension

• Office BP ≥ 180/110 mm Hg on treatment (at V0 visit)

• History of myocardial infarction, unstable angina, or cerebrovascular accident within the past 1 year

• CHF of class III-IV NYHA

• Type I diabetes or decompensated type 2 diabetes

• Diseases with severe organ dysfunction (hepatic failure, renal failure, etc.)

• Contraindications to or known intolerance of dihydropyridine calcium channel blockers (including amlodipine) and/or indapamide and/or ACE inhibitors (including perindopril) and/or their fixed combination

• Inability to understand the nature of the program and/or to follow the doctor's recommendations, including ones for the BP self-monitoring.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City Policlinic #3	Almetyevsk		Russian Federation
2	City Policlinic # 9	Barnaul		Russian Federation
3	City Policlinic # 7	Belgorod		Russian Federation
4	City Hospital # 2	Brjansk		Russian Federation
5	City Policlinic # 15	Chabarowsk		Russian Federation
6	City Policlinic # 8	Chelyabinsk		Russian Federation
7	City Policlinic # 2	Cherepovets		Russian Federation
8	City Policlinic # 3	Ekaterinburg		Russian Federation
9	City Policlinic # 8	Irkutsk		Russian Federation
10	City Policlinic # 5	Ivanovo		Russian Federation
11	City Hospital # 1	Izhevsk		Russian Federation
12	City Policlinic # 1	Jaroslavl		Russian Federation
13	City Policlinic # 18	Kazan		Russian Federation
14	City Policlinic # 5	Kemerovo		Russian Federation
15	City Policlinic # 2	Kirov		Russian Federation
16	City Policlinic # 7	Krasnoyarsk		Russian Federation
17	City Policlinic # 7	Kursk		Russian Federation
18	FSBI NMIC of Cardiology of the Ministry of Health of Russia	Moscow		Russian Federation	121552
19	City Policlinic # 70	Moscow		Russian Federation
20	City Policlinic # 2	Murmansk		Russian Federation
21	City Policlinic # 17	Nizhniy Novgorod		Russian Federation
22	City Hospital # 2	Novokuznetsk		Russian Federation
23	City Policlinic # 14	Novosibirsk		Russian Federation
24	City Policlinic # 2	Omsk		Russian Federation
25	Clinic PROM-MED	Orenburg		Russian Federation
26	City Policlinic # 2	Orël		Russian Federation
27	Policlinic of Regional Clinic Hospital	Penza		Russian Federation
28	Medical Center "Alfa-Center"	Perm		Russian Federation
29	City Policlinic # 4	Petrozavodsk		Russian Federation
30	City Policlinic # 3	Pskov		Russian Federation
31	City Policlinic # 42	Rostov-on-Don		Russian Federation
32	City Policlinic # 2	Ryazan'		Russian Federation
33	City Policlinic # 8	Samara		Russian Federation
34	City Policlinic # 27	Sankt-Peterburg		Russian Federation
35	City Policlinic # 2	Saratov		Russian Federation
36	City Policlinic # 2	Sevastopol		Russian Federation
37	Policlinic of Russian railway	Smolensk		Russian Federation
38	City Policlinic # 2	Stary Oskol		Russian Federation
39	City Policlinic # 3	Syktyvkar		Russian Federation
40	City Policlinic # 6	Tambov		Russian Federation
41	City Policlinic # 3	Tjumen		Russian Federation
42	City Policlinic # 2	Toljatti		Russian Federation
43	City Policlinic # 2	Tomsk		Russian Federation
44	Policlinic VIRMED	Tula		Russian Federation
45	City Policlinic # 46	Ufa		Russian Federation
46	City Policlinic # 4	Veliky Novgorod		Russian Federation
47	City Policlinic # 4	Vladimir		Russian Federation
48	City Policlinic # 4	Vladivostok		Russian Federation
49	City Policlinic # 15	Volgograd		Russian Federation
50	City Policlinic # 3	Vologda		Russian Federation
51	City Policlinic # 7	Voronezh		Russian Federation

Sponsors and Collaborators

• Servier Russia

Investigators

• Study Chair: Natatya LOGUNOVA,

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 25, 2018
• Informed Consent Form - Jun 25, 2018

More Information

Publications

None provided.

• Responsible Party: Servier Russia
• ClinicalTrials.gov Identifier: NCT03722524
• Other Study ID Numbers: IC4-06593-057-RUS
• First Posted: Oct 29, 2018
• Last Update Posted: Jun 10, 2021
• Last Verified: May 1, 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Hypertension; Amlodipine; Perindopril; Indapamide; Indapamide, perindopril drug combination; Diuretics; Angiotensin-Converting Enzyme Inhibitors

Study Results

Participant Flow

Arm/Group Title	Patients With Arterial Hypertension
Arm/Group Description	The patient is included in the program if prior to the study his/her doctor decided to adjust treatment, targeted at the BP control improvement, by prescription of a triple FDC of amlodipine / indapamide / perindopril arginine. The prescription of the triple FDC of amlodipine / indapamide / perindopril arginine during the program is made by the doctor's decision according to the instructions for medical use of this FDC. Presumably, each doctor will include 4 patients in average. It is planned to include 1,300 patients. amlodipine / indapamide / perindopril arginine FDC: CCB / diuretic / ACE inhibitor
Period Title: Overall Study
STARTED	1247
COMPLETED	1148
NOT COMPLETED	99

Baseline Characteristics

Arm/Group Title	Patients With Arterial Hypertension
Arm/Group Description	The patient is included in the program if prior to the study his/her doctor decided to adjust treatment, targeted at the BP control improvement, by prescription of a triple FDC of amlodipine / indapamide / perindopril arginine. The prescription of the triple FDC of amlodipine / indapamide / perindopril arginine during the program is made by the doctor's decision according to the instructions for medical use of this FDC. Presumably, each doctor will include 4 patients in average. It is planned to include 1,300 patients. amlodipine / indapamide / perindopril arginine FDC: CCB / diuretic / ACE inhibitor
Overall Participants	1148
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	810 70.6%
>=65 years	338 29.4%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.24 (10.48)
Sex: Female, Male (Count of Participants)
Female	687 59.8%
Male	451 39.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	0 0%
More than one race	0 0%
Unknown or Not Reported	1148 100%
Region of Enrollment (participants) [Number]
Russia	1148 100%
Patients with arterial hypertension (Count of Participants)
Count of Participants [Participants]	1148 100%

Outcome Measures

1. Primary Outcome

Title	The Mean Systolic BP Changes (mm Hg) at the Visit 4 vs. Baseline
Description	Changes in the mean office systolic BP levels (in mm Hg) in the sitting position Blood pressure was measured in accordance with the guidelines of the European Society of Hypertension (ESH) using the auscultatory or oscillometric method and a semi-automated sphygmomanometer. Before taking measurements, the patient remained in a sitting position for 3-5 minutes. Blood pressure was determined on each arm, and the arm with the highest value was taken as the reference. Measurements were taken thrice in the sitting position of a patient, and the average of the second and third BP measurements on the reference arm with an interval of at least 1-2 minutes was recorded.
Time Frame	Baseline, 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patients With Arterial Hypertension
Arm/Group Description	The patient is included in the program if prior to the study his/her doctor decided to adjust treatment, targeted at the BP control improvement, by prescription of a triple FDC of amlodipine / indapamide / perindopril arginine. The prescription of the triple FDC of amlodipine / indapamide / perindopril arginine during the program is made by the doctor's decision according to the instructions for medical use of this FDC. Presumably, each doctor will include 4 patients in average. It is planned to include 1,300 patients. amlodipine / indapamide / perindopril arginine FDC: CCB / diuretic / ACE inhibitor
Measure Participants	1148
Mean (Standard Deviation) [mm Hg]	33.47 (11.70)

2. Primary Outcome

Title	The Mean Diastolic BP Changes (mm Hg) at the Visit 4 vs Baseline.
Description	Changes in the mean office diastolic BP levels (in mm Hg) in the sitting position
Time Frame	Baseline, 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patients With Arterial Hypertension
Arm/Group Description	The patient is included in the program if prior to the study his/her doctor decided to adjust treatment, targeted at the BP control improvement, by prescription of a triple FDC of amlodipine / indapamide / perindopril arginine. The prescription of the triple FDC of amlodipine / indapamide / perindopril arginine during the program is made by the doctor's decision according to the instructions for medical use of this FDC. Presumably, each doctor will include 4 patients in average. It is planned to include 1,300 patients. amlodipine / indapamide / perindopril arginine FDC: CCB / diuretic / ACE inhibitor
Measure Participants	1148
Mean (Standard Deviation) [mm Hg]	14.34 (8.63)

3. Secondary Outcome

Title	Percentage of Patients Who Achieved the Target Office BP Levels (SBP <140 mm Hg and DBP <90 mm Hg) at Visit 4 vs Baseline
Description	The assessment of the target office BP levels (SBP <140 mm Hg and DBP <90 mm Hg) was performed in accordance with ESC Guidelines for the management of arterial hypertension (2013)
Time Frame	Baseline, 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patients With Arterial Hypertension
Arm/Group Description	The patient is included in the program if prior to the study his/her doctor decided to adjust treatment, targeted at the BP control improvement, by prescription of a triple FDC of amlodipine / indapamide / perindopril arginine. The prescription of the triple FDC of amlodipine / indapamide / perindopril arginine during the program is made by the doctor's decision according to the instructions for medical use of this FDC. Presumably, each doctor will include 4 patients in average. It is planned to include 1,300 patients. amlodipine / indapamide / perindopril arginine FDC: CCB / diuretic / ACE inhibitor
Measure Participants	1148
Number (95% Confidence Interval) [percentage of patients]	93.38

4. Secondary Outcome

Title	The Mean Standardized Score of the Physical Component of the Quality of Life Questionnaire The Short Form (36) Health Survey at Visit 4 vs Baseline
Description	Change in the mean score of the of the physical component of the The Short Form (36) Health Survey (SF-36) survey. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Time Frame	Baseline, 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patients With Arterial Hypertension
Arm/Group Description	The patient is included in the program if prior to the study his/her doctor decided to adjust treatment, targeted at the BP control improvement, by prescription of a triple FDC of amlodipine / indapamide / perindopril arginine. The prescription of the triple FDC of amlodipine / indapamide / perindopril arginine during the program is made by the doctor's decision according to the instructions for medical use of this FDC. Presumably, each doctor will include 4 patients in average. It is planned to include 1,300 patients. amlodipine / indapamide / perindopril arginine FDC: CCB / diuretic / ACE inhibitor
Measure Participants	1148
Mean (Standard Deviation) [score on a scale]	13.64 (18.06)

5. Secondary Outcome

Title	The Mean Standardized Score of the Mental Component of the Quality of Life Questionnaire The Short Form (36) Health Survey at Visit 4 vs Baseline
Description	Change in the mean score of the of the physical component of the SF-36 survey Change in the mean score of the of the physical component of the The Short Form (36) Health Survey (SF-36) survey. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Time Frame	Baseline, 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patients With Arterial Hypertension
Arm/Group Description	The patient is included in the program if prior to the study his/her doctor decided to adjust treatment, targeted at the BP control improvement, by prescription of a triple FDC of amlodipine / indapamide / perindopril arginine. The prescription of the triple FDC of amlodipine / indapamide / perindopril arginine during the program is made by the doctor's decision according to the instructions for medical use of this FDC. Presumably, each doctor will include 4 patients in average. It is planned to include 1,300 patients. amlodipine / indapamide / perindopril arginine FDC: CCB / diuretic / ACE inhibitor
Measure Participants	1148
Mean (Standard Deviation) [score on a scale]	23.57 (13.79)

Adverse Events

Time Frame	10 months
Arm/Group Title	Patients With Arterial Hypertension
Arm/Group Description	The patient is included in the program if prior to the study his/her doctor decided to adjust treatment, targeted at the BP control improvement, by prescription of a triple FDC of amlodipine / indapamide / perindopril arginine. The prescription of the triple FDC of amlodipine / indapamide / perindopril arginine during the program is made by the doctor's decision according to the instructions for medical use of this FDC. Presumably, each doctor will include 4 patients in average. It is planned to include 1,300 patients. amlodipine / indapamide / perindopril arginine FDC: CCB / diuretic / ACE inhibitor
All Cause Mortality
	Patients With Arterial Hypertension
	Affected / at Risk (%)	# Events
Total	0/1148 (0%)
Serious Adverse Events
	Patients With Arterial Hypertension
	Affected / at Risk (%)	# Events
Total	3/1148 (0.3%)
Immune system disorders
tooth abscess	1/1148 (0.1%)	1
exacerbation of chronic pyelonephritis	1/1148 (0.1%)	1
Vascular disorders
unstable angina	1/1148 (0.1%)	1
Other (Not Including Serious) Adverse Events
	Patients With Arterial Hypertension
	Affected / at Risk (%)	# Events
Total	9/1148 (0.8%)
Cardiac disorders
cough	5/1148 (0.4%)	5
Vascular disorders
arterial hypotension with BP of 80/50 mm Hg and weakness	1/1148 (0.1%)	1
treatment inefficacy	1/1148 (0.1%)	1
unstable angina	1/1148 (0.1%)	1
arterial hypotension	1/1148 (0.1%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.