Telmisartan/Amlodipine (80/10) vs. Telmisartan/Amlodipine (40/10) vs. amlodipine10 in Resistant Hypertension

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00553267
• Collaborator: (none)
• Enrollment: 947
• Locations: 97
• Patients Per Site: 9.8

Study Details

Study Description

Brief Summary

The primary objective of this trial is to demonstrate that the fixed dose combination of telmisartan 40mg + amlodipine 10mg (T40/A10) or the fixed dose combination of telmisartan 80mg + amlodipine 10mg (T80/A10) is superior in reducing blood pressure at eight weeks compared with amlodipine 10mg monotherapy (A10) in patients who fail to respond to six weeks treatment with A10.

Condition or Disease	Intervention/Treatment	Phase
Hypertension	Drug: fixed dose combination of telmisartan+amlodipine; Drug: amlodipine	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 947 participants
• Intervention Model: Parallel Assignment
• Primary Purpose: Treatment
• Official Title: An Eight-week Randomised, Double-blind Study to Compare the Fixed-dose Combination of Telmisartan 40mg + Amlodipine 10mg Versus Telmisartan 80mg + Amlodipine 10mg Versus Amlodipine 10mg Monotherapy in Patients With Hypertension Who Fail to Respond Adequately to Treatment With Amlodipine 10mg Monotherapy
• Study Start Date: Nov 1, 2007
• Actual Primary Completion Date: Oct 1, 2008

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Trough Seated Diastolic Blood Pressure [Baseline and end of study (8 weeks or last value on treatment)]

   Change from baseline to the end of study in trough DBP

Secondary Outcome Measures

1. Change From Baseline in Trough Seated Systolic Blood Pressure [Baseline and end of study (8 weeks or last value on treatment)]

   Change from baseline to the end of study in trough SBP

2. Trough Seated Diastolic Blood Pressure Control (Defined as < 90mmHg) [End of study (8 weeks or last value on treatment)]

   The number of patients who reach the target DBP of <90mmHg

3. Trough Seated Diastolic Blood Pressure <80 mmHg [End of study (8 weeks or last value on treatment)]

   The number of patients who reach the target DBP of <80mmHg

4. Trough Seated DBP Response [End of study (8 weeks or last value on treatment)]

   The number of patients who reach the target DBP of <90mmHg or had a reduction in DBP >= 10mmHg

5. Trough Seated SBP Control [End of study (8 weeks or last value on treatment)]

   The number of patients who reach the target SBP of <140mmHg

6. Trough Seated SBP Response [End of study (8 weeks or last value on treatment)]

   The number of patients who reach the target SBP of <140mmHg or had a reduction in SBP >= 15 mmHg

7. Trough Seated BP Normality Classes [End of study (8 weeks or last value on treatment)]

   The number of patients who reach predefined BP categories

8. Oedema Incidence Rate [During randomised treatment period]

   The number of patients who experienced at least one case of oedema or worsening of oedema for the first time (expressed as number of patients/100 patient-years)

9. Peripheral Oedema Incidence Rate [During randomised treatment period]

   The number of cases of peripheral oedema (expressed as number of cases/100 patient-years)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• diagnosis of essential hypertension and blood pressure not adequately controlled before informed consent (inadequate control defined as seated diastolic blood pressure (DBP) >= 95 mmHg if on existing antihypertensive treatment or seated DBP >= 100 mmHg if treatment-naïve).

• failure to respond to six weeks treatment with amlodipine 10mg. (Failure to respond defined as seated DBP >= 90 mmHg.)

• able to stop any current antihypertensive therapy without unacceptable risk to the patient.

• willing and able to provide written informed consent.

Exclusion Criteria:

• pregnancy, breast-feeding, unwilling to use effective contraception (if female of child-bearing potential).

• known or suspected secondary hypertension.

• mean seated systolic blood pressure (SBP) >=200 mmHg and/or mean seated DBP >= 120 mmHg during run-in treatment or mean seated SBP >= 180 mmHg and/or mean seated DBP >= 120 mmHg at the randomisation visit or at any time during randomised treatment.

• any clinically significant hepatic impairment or severe renal impairment bilateral renal artery stenosis or renal artery stenosis in a solitary kidney or post post-renal transplant.

• clinically relevant hyperkalaemia.

• uncorrected volume or sodium depletion.

• primary aldosteronism.

• hereditary fructose or lactose intolerance.

• symptomatic congestive heart failure.

• patients who have previously experienced symptoms characteristic of angioedema during treatment with ACE inhibitors or ARBs.

• history of drug or alcohol dependency within the six months prior to signing consent.

• concurrent participation in another clinical trial or any investigational therapy within thirty days prior to signing consent.

• hypertrophic obstructive cardiomyopathy, hemodynamically relevant stenosis of the aortic or mitral valve.

• known allergic hypersensitivity to any component of the formulations under investigation. (Includes known hypersensitivity to telmisartan or other ARBs or amlodipine or other dihydropyridine CCBs.)

• non-compliance with study medication (defined as less than 80% or more than 120%) during the open-label run-in treatment period.

• current treatment with any antihypertensive agents, whether or not prescribed for this indication, that cannot be safely stopped (investigator¿s decision) by the start of the run-in period.

• chronic administration of any medication known to affect blood pressure, other than the trial medication.

• any other clinical condition which, in the opinion of the investigator, would not allow safe completion of the protocol and safe administration of telmisartan and amlodipine.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	1235.6.61003 Boehringer Ingelheim Investigational Site	Gosford	New South Wales	Australia
2	1235.6.61004 Boehringer Ingelheim Investigational Site	Liverpool	New South Wales	Australia
3	1235.6.61002 Boehringer Ingelheim Investigational Site	Kippa-Ring	Queensland	Australia
4	1235.6.61001 Boehringer Ingelheim Investigational Site	Milton	Queensland	Australia
5	1235.6.61005 Boehringer Ingelheim Investigational Site	Elizabeth Vale	South Australia	Australia
6	1235.6.43007 Boehringer Ingelheim Investigational Site	Eggenburg		Austria
7	1235.6.43006 Boehringer Ingelheim Investigational Site	Hainburg a.d. Donau		Austria
8	1235.6.43005 Boehringer Ingelheim Investigational Site	Hartberg		Austria
9	1235.6.43001 Boehringer Ingelheim Investigational Site	Wien		Austria
10	1235.6.43002 Boehringer Ingelheim Investigational Site	Wien		Austria
11	1235.6.43003 Boehringer Ingelheim Investigational Site	Wien		Austria
12	1235.6.35912 Boehringer Ingelheim Investigational Site	Bourgas		Bulgaria
13	1235.6.35902 Boehringer Ingelheim Investigational Site	Sofia		Bulgaria
14	1235.6.35903 Boehringer Ingelheim Investigational Site	Sofia		Bulgaria
15	1235.6.35904 Boehringer Ingelheim Investigational Site	Sofia		Bulgaria
16	1235.6.35905 Boehringer Ingelheim Investigational Site	Sofia		Bulgaria
17	1235.6.35906 Boehringer Ingelheim Investigational Site	Sofia		Bulgaria
18	1235.6.35907 Boehringer Ingelheim Investigational Site	Sofia		Bulgaria
19	1235.6.35910 Boehringer Ingelheim Investigational Site	Sofia		Bulgaria
20	1235.6.35911 Boehringer Ingelheim Investigational Site	Sofia		Bulgaria
21	1235.6.35901 Boehringer Ingelheim Investigational Site	Varna		Bulgaria
22	1235.6.42002 Boehringer Ingelheim Investigational Site	Benatky nad Jizerou		Czech Republic
23	1235.6.42006 Boehringer Ingelheim Investigational Site	Brno		Czech Republic
24	1235.6.42001 Boehringer Ingelheim Investigational Site	Plzen		Czech Republic
25	1235.6.42003 Boehringer Ingelheim Investigational Site	Praha 5		Czech Republic
26	1235.6.42004 Boehringer Ingelheim Investigational Site	Pribram		Czech Republic
27	1235.6.42005 Boehringer Ingelheim Investigational Site	Slany		Czech Republic
28	1235.6.42007 Boehringer Ingelheim Investigational Site	Strakonice		Czech Republic
29	1235.6.35304 Wilmer Road	Birr		Ireland
30	1235.6.35305 Dr. Ger McLaughlin	Carrigtwohill		Ireland
31	1235.6.35302 Slaney Medical Centre	Enniscorthy		Ireland
32	1235.6.35303 Gorey Medical Centre, Coral House,	Gorey		Ireland
33	1235.6.35306 The Red House Surgery	Mallow		Ireland
34	1235.6.35301 Boehringer Ingelheim Investigational Site	New Ross		Ireland
35	1235.6.39002 Boehringer Ingelheim Investigational Site	Broni (pv)		Italy
36	1235.6.39006 Boehringer Ingelheim Investigational Site	Coppito (AQ)		Italy
37	1235.6.39001 Boehringer Ingelheim Investigational Site	Ferrara		Italy
38	1235.6.64003 Boehringer Ingelheim Investigational Site	Dunedin		New Zealand
39	1235.6.64002 Boehringer Ingelheim Investigational Site	Otahuhu, Auckland		New Zealand
40	1235.6.64001 Boehringer Ingelheim Investigational Site	Tauranga		New Zealand
41	1235.6.70004 Boehringer Ingelheim Investigational Site	Moscow		Russian Federation
42	1235.6.70005 Boehringer Ingelheim Investigational Site	Moscow		Russian Federation
43	1235.6.70006 Boehringer Ingelheim Investigational Site	Moscow		Russian Federation
44	1235.6.70007 Boehringer Ingelheim Investigational Site	Moscow		Russian Federation
45	1235.6.70008 Boehringer Ingelheim Investigational Site	Moscow		Russian Federation
46	1235.6.70009 Boehringer Ingelheim Investigational Site	Moscow		Russian Federation
47	1235.6.70010 Boehringer Ingelheim Investigational Site	St. Petersburg		Russian Federation
48	1235.6.70011 Boehringer Ingelheim Investigational Site	St. Petersburg		Russian Federation
49	1235.6.70012 Boehringer Ingelheim Investigational Site	St. Petersburg		Russian Federation
50	1235.6.42103 Boehringer Ingelheim Investigational Site	Dolny Kubin		Slovakia
51	1235.6.42106 Boehringer Ingelheim Investigational Site	Kralovsky Chmlec		Slovakia
52	1235.6.42104 Boehringer Ingelheim Investigational Site	Liptovsky Mikulas		Slovakia
53	1235.6.42102 Boehringer Ingelheim Investigational Site	Povazska Bystrica		Slovakia
54	1235.6.42105 Boehringer Ingelheim Investigational Site	Presov		Slovakia
55	1235.6.42101 Boehringer Ingelheim Investigational Site	Trencin		Slovakia
56	1235.6.42107 Boehringer Ingelheim Investigational Site	Vrable		Slovakia
57	1235.6.34008 Hospital Municipal de Badalona	Badalona		Spain
58	1235.6.34009 Boehringer Ingelheim Investigational Site	Barcelona		Spain
59	1235.6.34001 Hospital Gral de Jerez de la Frontera	Jerez de la Frontera (Cádiz)		Spain
60	1235.6.34006 C.A.P. Mossen Cinto Verdaguer	L'Hospitalet de Llobregat (Barcelona)		Spain
61	1235.6.34003 Hospital Doce de Octubre	Madrid		Spain
62	1235.6.34004 Hospital La Princesa	Madrid		Spain
63	1235.6.34011 Boehringer Ingelheim Investigational Site	Santa Coloma de Gramanet		Spain
64	1235.6.41005 Boehringer Ingelheim Investigational Site	Gordola		Switzerland
65	1235.6.90004 Boehringer Ingelheim Investigational Site	Erzurum		Turkey
66	1235.6.90003 Boehringer Ingelheim Investigational Site	Istanbul		Turkey
67	1235.6.90005 Boehringer Ingelheim Investigational Site	Istanbul		Turkey
68	1235.6.90001 Boehringer Ingelheim Investigational Site	Izmir		Turkey
69	1235.6.38010 Boehringer Ingelheim Investigational Site	Dnepropetrovsk		Ukraine
70	1235.6.38001 Boehringer Ingelheim Investigational Site	Kharkov		Ukraine
71	1235.6.38003 Boehringer Ingelheim Investigational Site	Kharkov		Ukraine
72	1235.6.38008 Boehringer Ingelheim Investigational Site	Kharkov		Ukraine
73	1235.6.38011 Boehringer Ingelheim Investigational Site	Kharkov		Ukraine
74	1235.6.38004 Boehringer Ingelheim Investigational Site	Kiev		Ukraine
75	1235.6.38006 Boehringer Ingelheim Investigational Site	Kiev		Ukraine
76	1235.6.38012 Boehringer Ingelheim Investigational Site	Kiev		Ukraine
77	1235.6.38013 Boehringer Ingelheim Investigational Site	Kiev		Ukraine
78	1235.6.38002 Boehringer Ingelheim Investigational Site	Lvov		Ukraine
79	1235.6.38005 Boehringer Ingelheim Investigational Site	Odessa		Ukraine
80	1235.6.38009 Boehringer Ingelheim Investigational Site	Odessa		Ukraine
81	1235.6.38007 Boehringer Ingelheim Investigational Site	Zaporozhye		Ukraine
82	1235.6.44010 Boehringer Ingelheim Investigational Site	Bexhill		United Kingdom
83	1235.6.44008 Boehringer Ingelheim Investigational Site	Blackpool		United Kingdom
84	1235.6.44016 Boehringer Ingelheim Investigational Site	Blackpool		United Kingdom
85	1235.6.44011 Boehringer Ingelheim Investigational Site	Burbage, Hinkley		United Kingdom
86	1235.6.44007 Boehringer Ingelheim Investigational Site	Chestfield, Whitstable		United Kingdom
87	1235.6.44005 Boehringer Ingelheim Investigational Site	Chorley		United Kingdom
88	1235.6.44002 Boehringer Ingelheim Investigational Site	Edgbaston, Birmingham		United Kingdom
89	1235.6.44009 Boehringer Ingelheim Investigational Site	Ely		United Kingdom
90	1235.6.44001 Boehringer Ingelheim Investigational Site	Fowey		United Kingdom
91	1235.6.44003 Boehringer Ingelheim Investigational Site	Glasgow		United Kingdom
92	1235.6.44012 Boehringer Ingelheim Investigational Site	Penzance		United Kingdom
93	1235.6.44013 Boehringer Ingelheim Investigational Site	Plymouth		United Kingdom
94	1235.6.44004 Boehringer Ingelheim Investigational Site	Reading		United Kingdom
95	1235.6.44014 Boehringer Ingelheim Investigational Site	Saltash		United Kingdom
96	1235.6.44015 Boehringer Ingelheim Investigational Site	St Stephen, St Austell		United Kingdom
97	1235.6.44006 Boehringer Ingelheim Investigational Site	Whitstable		United Kingdom

Sponsors and Collaborators

• Boehringer Ingelheim

Investigators

• Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info
• Related Info

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00553267
• Other Study ID Numbers: 1235.6; EUDRACT 2007-002421-68
• First Posted: Nov 4, 2007
• Last Update Posted: Feb 13, 2014
• Last Verified: Dec 1, 2013

• Additional relevant MeSH terms: Hypertension; Amlodipine; Telmisartan; Telmisartan amlodipine combination

Study Results

Participant Flow

Arm/Group Title	Amlodipine 10mg	Telmisartan 40mg and Amlodipine 10mg	Telmisartan 80mg and Amlodipine 10mg
Arm/Group Description
Period Title: Overall Study
STARTED	315	315	317
COMPLETED	301	297	307
NOT COMPLETED	14	18	10

Baseline Characteristics

Arm/Group Title	Amlodipine 10mg	Telmisartan 40mg and Amlodipine 10mg	Telmisartan 80mg and Amlodipine 10mg	Total
Arm/Group Description	Total of all reporting groups
Overall Participants	315	315	317	947
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	56.4 (10.4)	57.6 (9.4)	55.5 (9.8)	56.5 (9.9)
Sex: Female, Male (Count of Participants)
Female	128 40.6%	145 46%	146 46.1%	419 44.2%
Male	187 59.4%	170 54%	171 53.9%	528 55.8%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Trough Seated Diastolic Blood Pressure
Description	Change from baseline to the end of study in trough DBP
Time Frame	Baseline and end of study (8 weeks or last value on treatment)

Outcome Measure Data

Analysis Population Description

Full analysis set of patients who had a baseline trough blood pressure measurement and at least one post baseline trough blood pressure measurement using last observation carried forward

Arm/Group Title	Amlodipine 10mg	Telmisartan 40mg and Amlodipine 10mg	Telmisartan 80mg and Amlodipine 10mg
Arm/Group Description
Measure Participants	305	306	310
Least Squares Mean (Standard Error) [mmHg]	-6.48 (0.45)	-9.24 (0.45)	-9.33 (0.45)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Amlodipine 10mg, Telmisartan 40mg and Amlodipine 10mg
	Comments	Testing that the combination treatments are superior to monotherapy A10. The number of patients in the treatment arms ensure the tests have over 90% power.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Doses tested against A10 in a hierarchical manner to address issues of multiplicity. T80/A10 was tested first, then T40/A10.
	Method	ANCOVA
	Comments	Adjusted for baseline and country effect
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-2.76
	Confidence Interval	() 95%; -3.77 to -1.75
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.52
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Amlodipine 10mg, Telmisartan 80mg and Amlodipine 10mg
	Comments	Testing that the combination treatments are superior to monotherapy A10. The number of patients in the treatment arms ensure the tests have over 90% power.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Doses tested against A10 in a hierarchical manner to address issues of multiplicity. T80/A10 was tested first, then T40/A10.
	Method	ANCOVA
	Comments	Adjusted for baseline and country effect
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-2.85
	Confidence Interval	() 95%; -3.86 to -1.84
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.51
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in Trough Seated Systolic Blood Pressure
Description	Change from baseline to the end of study in trough SBP
Time Frame	Baseline and end of study (8 weeks or last value on treatment)

Outcome Measure Data

Analysis Population Description

Full analysis set of patients who had a baseline trough blood pressure measurement and at least one post baseline trough blood pressure measurement using last observation carried forward

Arm/Group Title	Amlodipine 10mg	Telmisartan 40mg and Amlodipine 10mg	Telmisartan 80mg and Amlodipine 10mg
Arm/Group Description
Measure Participants	305	306	310
Least Squares Mean (Standard Error) [mmHg]	-7.44 (0.66)	-11.09 (0.66)	-11.29 (0.66)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Amlodipine 10mg, Telmisartan 40mg and Amlodipine 10mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	Adjusted for baseline and country effect
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-3.66
	Confidence Interval	() 95%; -5.15 to -2.16
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.76
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Amlodipine 10mg, Telmisartan 80mg and Amlodipine 10mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	Adjusted for baseline and country effect
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-3.85
	Confidence Interval	() 95%; -5.35 to -2.36
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.76
	Estimation Comments

3. Secondary Outcome

Title	Trough Seated Diastolic Blood Pressure Control (Defined as < 90mmHg)
Description	The number of patients who reach the target DBP of <90mmHg
Time Frame	End of study (8 weeks or last value on treatment)

Outcome Measure Data

Analysis Population Description

Full analysis set of patients who had a baseline trough blood pressure measurement and at least one post baseline trough blood pressure measurement using last observation carried forward

Arm/Group Title	Amlodipine 10mg	Telmisartan 40mg and Amlodipine 10mg	Telmisartan 80mg and Amlodipine 10mg
Arm/Group Description
Measure Participants	305	306	310
Yes (DBP<90 mmHg)	156 49.5%	195 61.9%	206 65%
No (DBP>=90 mmHg)	149 47.3%	111 35.2%	104 32.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Amlodipine 10mg, Telmisartan 40mg and Amlodipine 10mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	Mantel Haenszel
	Comments	Mantel-Haenszel statistics adjusted for country effect
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.67
	Confidence Interval	(2-Sided) 95%; 1.21 to 2.32
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Amlodipine 10mg, Telmisartan 80mg and Amlodipine 10mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mantel Haenszel
	Comments	Mantel-Haenszel statistics adjusted for country effect
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.91
	Confidence Interval	() 95%; 1.37 to 2.65
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Trough Seated Diastolic Blood Pressure <80 mmHg
Description	The number of patients who reach the target DBP of <80mmHg
Time Frame	End of study (8 weeks or last value on treatment)

Outcome Measure Data

Analysis Population Description

Full analysis set of patients who had a baseline trough blood pressure measurement and at least one post baseline trough blood pressure measurement using last observation carried forward

Arm/Group Title	Amlodipine 10mg	Telmisartan 40mg and Amlodipine 10mg	Telmisartan 80mg and Amlodipine 10mg
Arm/Group Description
Measure Participants	305	306	310
Yes (DBP<80 mmHg)	18 5.7%	39 12.4%	39 12.3%
No (DBP>=80 mmHg)	287 91.1%	267 84.8%	271 85.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Amlodipine 10mg, Telmisartan 40mg and Amlodipine 10mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments
	Method	Mantel Haenszel
	Comments	Mantel-Haenszel statistics adjusted for country effect
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.35
	Confidence Interval	() 95%; 1.30 to 4.25
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Amlodipine 10mg, Telmisartan 80mg and Amlodipine 10mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments
	Method	Mantel Haenszel
	Comments	Mantel-Haenszel statistics adjusted for country effect
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.33
	Confidence Interval	() 95%; 1.29 to 4.22
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Trough Seated DBP Response
Description	The number of patients who reach the target DBP of <90mmHg or had a reduction in DBP >= 10mmHg
Time Frame	End of study (8 weeks or last value on treatment)

Outcome Measure Data

Analysis Population Description

Full analysis set of patients who had a baseline trough blood pressure measurement and at least one post baseline trough blood pressure measurement using last observation carried forward

Arm/Group Title	Amlodipine 10mg	Telmisartan 40mg and Amlodipine 10mg	Telmisartan 80mg and Amlodipine 10mg
Arm/Group Description
Measure Participants	305	306	310
Yes (Responder)	163 51.7%	202 64.1%	213 67.2%
No (Non-responder)	142 45.1%	104 33%	97 30.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Amlodipine 10mg, Telmisartan 40mg and Amlodipine 10mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	Mantel Haenszel
	Comments	Mantel-Haenszel statistics adjusted for country effect
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.68
	Confidence Interval	() 95%; 1.21 to 2.34
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Amlodipine 10mg, Telmisartan 80mg and Amlodipine 10mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mantel Haenszel
	Comments	Mantel-Haenszel statistics adjusted for country effect
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.92
	Confidence Interval	() 95%; 1.38 to 2.68
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Trough Seated SBP Control
Description	The number of patients who reach the target SBP of <140mmHg
Time Frame	End of study (8 weeks or last value on treatment)

Outcome Measure Data

Analysis Population Description

Full analysis set of patients who had a baseline trough blood pressure measurement and at least one post baseline trough blood pressure measurement using last observation carried forward

Arm/Group Title	Amlodipine 10mg	Telmisartan 40mg and Amlodipine 10mg	Telmisartan 80mg and Amlodipine 10mg
Arm/Group Description
Measure Participants	305	306	310
Yes (SBP<140 mmHg)	153 48.6%	180 57.1%	187 59%
No (SBP>=140 mmHg)	152 48.3%	126 40%	123 38.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Amlodipine 10mg, Telmisartan 40mg and Amlodipine 10mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.027
	Comments
	Method	Mantel Haenszel
	Comments	Mantel-Haenszel statistics adjusted for country effect
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.44
	Confidence Interval	() 95%; 1.04 to 2.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Amlodipine 10mg, Telmisartan 80mg and Amlodipine 10mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.008
	Comments
	Method	Mantel Haenszel
	Comments	Mantel-Haenszel statistics adjusted for country effect
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.55
	Confidence Interval	() 95%; 1.12 to 2.15
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Trough Seated SBP Response
Description	The number of patients who reach the target SBP of <140mmHg or had a reduction in SBP >= 15 mmHg
Time Frame	End of study (8 weeks or last value on treatment)

Outcome Measure Data

Analysis Population Description

Full analysis set of patients who had a baseline trough blood pressure measurement and at least one post baseline trough blood pressure measurement using last observation carried forward

Arm/Group Title	Amlodipine 10mg	Telmisartan 40mg and Amlodipine 10mg	Telmisartan 80mg and Amlodipine 10mg
Arm/Group Description
Measure Participants	305	306	310
Yes (Responder)	165 52.4%	198 62.9%	204 64.4%
No (Non-responder)	140 44.4%	108 34.3%	106 33.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Amlodipine 10mg, Telmisartan 40mg and Amlodipine 10mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.006
	Comments
	Method	Mantel Haenszel
	Comments	Mantel-Haenszel statistics adjusted for country effect
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.58
	Confidence Interval	() 95%; 1.14 to 2.21
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Amlodipine 10mg, Telmisartan 80mg and Amlodipine 10mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	Mantel Haenszel
	Comments	Mantel-Haenszel statistics adjusted for country effect
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.67
	Confidence Interval	() 95%; 1.20 to 2.32
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Trough Seated BP Normality Classes
Description	The number of patients who reach predefined BP categories
Time Frame	End of study (8 weeks or last value on treatment)

Outcome Measure Data

Analysis Population Description

Full analysis set of patients who had a baseline trough blood pressure measurement and at least one post baseline trough blood pressure measurement using last observation carried forward

Arm/Group Title	Amlodipine 10mg	Telmisartan 40mg and Amlodipine 10mg	Telmisartan 80mg and Amlodipine 10mg
Arm/Group Description
Measure Participants	305	306	310
Optimal (SBP<120 and DBP<80 mmHg)	0 0%	12 3.8%	6 1.9%
Normal (SBP<130 and DBP<85 mmHg and not optimal)	36 11.4%	43 13.7%	50 15.8%
High-normal (SBP<140 DBP<90 mmHg and not normal)	77 24.4%	91 28.9%	106 33.4%
Stage 1 hypertension (SBP<160 and DBP<100 mmHg)	157 49.8%	139 44.1%	133 42%
Stage 2 hypertension (SBP>=160 and DBP>=100 mmHg)	35 11.1%	21 6.7%	15 4.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Amlodipine 10mg, Telmisartan 40mg and Amlodipine 10mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.006
	Comments
	Method	Wilcoxon rank sum test
	Comments	Stratified (for country) Wilcoxon rank sum test

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Amlodipine 10mg, Telmisartan 80mg and Amlodipine 10mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon rank sum test
	Comments	Stratified (for country) Wilcoxon rank sum test

9. Secondary Outcome

Title	Oedema Incidence Rate
Description	The number of patients who experienced at least one case of oedema or worsening of oedema for the first time (expressed as number of patients/100 patient-years)
Time Frame	During randomised treatment period

Outcome Measure Data

Analysis Population Description

Full analysis set of patients who had a baseline trough blood pressure measurement and at least one post baseline trough blood pressure measurement using last observation carried forward

Arm/Group Title	Amlodipine 10mg	Telmisartan 40mg and Amlodipine 10mg	Telmisartan 80mg and Amlodipine 10mg
Arm/Group Description
Measure Participants	305	306	310
Number [Number of patients/100 patient-years]	44.7	42.8	54.0

10. Secondary Outcome

Title	Peripheral Oedema Incidence Rate
Description	The number of cases of peripheral oedema (expressed as number of cases/100 patient-years)
Time Frame	During randomised treatment period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Amlodipine 10mg	Telmisartan 40mg and Amlodipine 10mg	Telmisartan 80mg and Amlodipine 10mg
Arm/Group Description
Measure Participants	305	306	310
Number [Number of cases/100 patient-years]	48.8	44.8	54.0

Adverse Events

Arm/Group Title	Amlodipine 10mg		Telmisartan 40mg and Amlodipine 10mg		Telmisartan 80mg and Amlodipine 10mg
Arm/Group Description
All Cause Mortality
	Amlodipine 10mg		Telmisartan 40mg and Amlodipine 10mg		Telmisartan 80mg and Amlodipine 10mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Amlodipine 10mg		Telmisartan 40mg and Amlodipine 10mg		Telmisartan 80mg and Amlodipine 10mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/ (NaN)		3/ (NaN)		0/ (NaN)
Cardiac disorders
Cardiac failure	0/315 (0%)		1/315 (0.3%)		0/317 (0%)
General disorders
Local swelling	0/315 (0%)		1/315 (0.3%)		0/317 (0%)
Infections and infestations
Bronchitis	1/315 (0.3%)		0/315 (0%)		0/317 (0%)
Nervous system disorders
Ruptured cerebral aneurysm	0/315 (0%)		1/315 (0.3%)		0/317 (0%)
Other (Not Including Serious) Adverse Events
	Amlodipine 10mg		Telmisartan 40mg and Amlodipine 10mg		Telmisartan 80mg and Amlodipine 10mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/ (NaN)		21/ (NaN)		27/ (NaN)
General disorders
Peripheral oedema	22/315 (7%)		21/315 (6.7%)		27/317 (8.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.