Effectiveness and Safety of Ramipril Alone Compared With Telmisartan Alone and in Combination With Ramipril in Patients at High Risk for Cardiovascular Events. Patients Intolerant to Ramipril Were Entered in TRANSCEND, Telmisartan Compared to Placebo. - Study Results

Study Type:	Interventional
Study Design:	Parallel Assignment
Condition:	Cardiovascular Diseases
Interventions:	Drug: Telmisartan Drug: Combination of Telmisartan and Ramipril Drug: Ramipril

	Description
Telmisartan/Ramipril (ONTARGET)	Telmisartan 80mg tablet / Ramipril 10mg tablet One tablet of each at the same time daily
Telmisartan (ONTARGET)	Telmisatan 80mg tablet /Ramipril 10mg placebo tablet One tablet of each at the same time daily
Ramipril (ONTARGET)	Ramipril 10mg tablet / Telmisartan 80mg placebo tablet One tablet of each at the same time daily
Telmisartan (TRANSCEND)	Telmisartan 80mg tablet one tablet daily
Placebo (TRANSCEND)	Telmisartan 80mg placebo tablet one tablet daily

	Telmisartan/Ramipril (ONTARGET)	Telmisartan (ONTARGET)	Ramipril (ONTARGET)	Telmisartan (TRANSCEND)	Placebo (TRANSCEND)
STARTED	8502	8542	8576	2954	2972
COMPLETED	8485	8524	8561	2946	2962
NOT COMPLETED	17	18	15	8	10
Lost to Follow-up	14	14	12	5	5
Withdrawal by Subject	3	4	3	3	5

	Description
Telmisartan/Ramipril (ONTARGET)	Telmisartan 80mg tablet / Ramipril 10mg tablet One tablet of each at the same time daily
Telmisartan (ONTARGET)	Telmisatan 80mg tablet /Ramipril 10mg placebo tablet One tablet of each at the same time daily
Ramipril (ONTARGET)	Ramipril 10mg tablet / Telmisartan 80mg placebo tablet One tablet of each at the same time daily
Telmisartan (TRANSCEND)	Telmisartan 80mg tablet one tablet daily
Placebo (TRANSCEND)	Telmisartan 80mg placebo tablet one tablet daily

	Telmisartan/Ramipril (ONTARGET)	Telmisartan (ONTARGET)	Ramipril (ONTARGET)	Telmisartan (TRANSCEND)	Placebo (TRANSCEND)	Total
Number of Participants [units: participants]	8502	8542	8576	2954	2972	31546
Age [units: years] Mean ± Standard Deviation	66.4 ± 7.3	66.4 ± 7.1	66.4 ± 7.2	66.9 ± 7.3	66.9 ± 7.4	66.5 ± 7.2
Gender [units: participants]
Female	2250	2250	2331	1280	1267	9378
Male	6252	6292	6245	1674	1705	22168

Outcome Measures

1. Primary:

ONTARGET. Composite Endpoint of Cardiovascular Death, Non-fatal Myocardial Infarction, Non-fatal Stroke and Hospitalization for Congestive Heart Failure [ 56 months ]

Show Outcome Measure 1

2. Primary:

TRANSCEND. Composite Endpoint of Cardiovascular Death, Non-fatal Myocardial Infarction, Non-fatal Stroke and Hospitalization for Congestive Heart Failure [ 56 months ]

Show Outcome Measure 2

3. Secondary:

ONTARGET. Composite Endpoint of Cardiovascular Death, Non-fatal Myocardial Infarction and Non-fatal Stroke [ 56 months ]

Hide Outcome Measure 3

Measure Type	Secondary
Measure Title	ONTARGET. Composite Endpoint of Cardiovascular Death, Non-fatal Myocardial Infarction and Non-fatal Stroke
Measure Description	The Ongoing Telmisartan Alone and combination with Ramipril global Endpoint trial (ONTARGET). Time to first event analysis of the following defined endpoints, non-fatal myocardial infarction or non-fatal stroke
Time Frame	56 months
Safety Issue

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

	Description
Telmisartan/Ramipril (ONTARGET)	No text entered.
Telmisartan (ONTARGET)	No text entered.
Ramipril (ONTARGET)	No text entered.

Measured Values

	Telmisartan/Ramipril (ONTARGET)	Telmisartan (ONTARGET)	Ramipril (ONTARGET)
Number of Participants Analyzed [units: participants]	8502	8542	8576
ONTARGET. Composite Endpoint of Cardiovascular Death, Non-fatal Myocardial Infarction and Non-fatal Stroke [units: participants]	1200	1190	1210

Statistical Analysis 1 for ONTARGET. Composite Endpoint of Cardiovascular Death, Non-fatal Myocardial Infarction and Non-fatal Stroke

Groups ^[1]	Telmisartan (ONTARGET) vs. Ramipril (ONTARGET)
Non-Inferiority/Equivalence Test ^[2]	Yes
Method ^[3]	Regression, Cox
P Value ^[4]	0.0004
Hazard Ratio (HR) ^[5]	0.99
97.5% Confidence Interval	( 0.90 to 1.08 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Details of power calculation, definition of non-inferiority margin, and other key parameters:
	Non-inferiority margin was 1.13
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for ONTARGET. Composite Endpoint of Cardiovascular Death, Non-fatal Myocardial Infarction and Non-fatal Stroke

Groups ^[1]	Telmisartan/Ramipril (ONTARGET) vs. Ramipril (ONTARGET)
Method ^[2]	Regression, Cox
P Value ^[3]	0.9086
Hazard Ratio (HR) ^[4]	1.00
95% Confidence Interval	( 0.93 to 1.09 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	No text entered.

4. Secondary:

ONTARGET. Cardiovascular Death [ 56 months ]

Show Outcome Measure 4

5. Secondary:

ONTARGET. Non-fatal Myocardial Infarction [ 56 months ]

Show Outcome Measure 5

6. Secondary:

ONTARGET. Non-fatal Stroke [ 56 months ]

Show Outcome Measure 6

7. Secondary:

ONTARGET. Hospitalization for Congestive Heart Failure [ 56 months ]

Show Outcome Measure 7

8. Secondary:

ONTARGET. Newly Diagnosed Congestive Heart Failure [ 56 months ]

Show Outcome Measure 8

9. Secondary:

ONTARGET. Cardiovascular Revascularization Procedure [ 56 months ]

Show Outcome Measure 9

10. Secondary:

ONTARGET. Newly Diagnosed Diabetes [ 56 months ]

Show Outcome Measure 10

11. Secondary:

ONTARGET. Cognitive Decline [ 56 months ]

Show Outcome Measure 11

12. Secondary:

ONTARGET. New Onset of Atrial Fibrillation [ 56 months ]

Show Outcome Measure 12

13. Secondary:

TRANSCEND. Composite Endpoint of Cardiovascular Death, Non-fatal Myocardial Infarction and Non-fatal Stroke [ 56 months ]

Show Outcome Measure 13

14. Secondary:

TRANSCEND. Cardiovascular Death [ 56 months ]

Show Outcome Measure 14

15. Secondary:

TRANSCEND. Non-fatal Myocardial Infarction [ 56 months ]

Show Outcome Measure 15

16. Secondary:

TRANSCEND. Non-fatal Stroke [ 56 months ]

Show Outcome Measure 16

17. Secondary:

TRANSCEND. Hospitalization for Congestive Heart Failure [ 56 months ]

Show Outcome Measure 17

18. Secondary:

TRANSCEND. Newly Diagnosed Congestive Heart Failure [ 56 months ]

Show Outcome Measure 18

19. Secondary:

TRANSCEND. Cardiovascular Revascularization Procedure [ 56 months ]

Show Outcome Measure 19

20. Secondary:

TRANSCEND. Newly Diagnosed Diabetes [ 56 months ]

Show Outcome Measure 20

21. Secondary:

TRANSCEND. Cognitive Decline [ 56 months ]

Show Outcome Measure 21

22. Secondary:

TRANSCEND. New Onset of Atrial Fibrillation [ 56 months ]

Show Outcome Measure 22

More Information

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Certain Agreements:

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

There IS 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.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: 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.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Only non-serious Adverse Events (AE) which lead to discontinuation of study medication were assessed and collected; the frequency was under 5%. Non-serious AEs per se were not assessed or collected.

Results Point of Contact:

Name/Title: Boehringer Ingelheim Call Center
Organization: Boehringer Ingelheim Pharmaceuticals
phone: 1-800-243-0127
e-mail: clintriage.rdg@boehringer-ingelheim.com

No publications provided by Boehringer Ingelheim Pharmaceuticals

Publications automatically indexed to this study:

Verdecchia P, Sleight P, Mancia G, Fagard R, Trimarco B, Schmieder RE, Kim JH, Jennings G, Jansky P, Chen JH, Liu L, Gao P, Probstfield J, Teo K, Yusuf S; ONTARGET/TRANSCEND Investigators. Effects of telmisartan, ramipril, and their combination on left ventricular hypertrophy in individuals at high vascular risk in the Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial and the Telmisartan Randomized Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease. Circulation. 2009 Oct 6;120(14):1380-9. Epub 2009 Sep 21.

Sleight P, Redon J, Verdecchia P, Mancia G, Gao P, Fagard R, Schumacher H, Weber M, Böhm M, Williams B, Pogue J, Koon T, Yusuf S; ONTARGET investigators. Prognostic value of blood pressure in patients with high vascular risk in the Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial study. J Hypertens. 2009 Jul;27(7):1360-9.

Mann JF, Schmieder RE, Dyal L, McQueen MJ, Schumacher H, Pogue J, Wang X, Probstfield JL, Avezum A, Cardona-Munoz E, Dagenais GR, Diaz R, Fodor G, Maillon JM, Rydén L, Yu CM, Teo KK, Yusuf S; TRANSCEND (Telmisartan Randomised Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease) Investigators. Effect of telmisartan on renal outcomes: a randomized trial. Ann Intern Med. 2009 Jul 7;151(1):1-10, W1-2. Epub 2009 May 18.

Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease (TRANSCEND) Investigators; Yusuf S, Teo K, Anderson C, Pogue J, Dyal L, Copland I, Schumacher H, Dagenais G, Sleight P. Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomised controlled trial. Lancet. 2008 Sep 27;372(9644):1174-83. Epub 2008 Aug 29.

Mann JF, Schmieder RE, McQueen M, Dyal L, Schumacher H, Pogue J, Wang X, Maggioni A, Budaj A, Chaithiraphan S, Dickstein K, Keltai M, Metsärinne K, Oto A, Parkhomenko A, Piegas LS, Svendsen TL, Teo KK, Yusuf S; ONTARGET investigators. Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial. Lancet. 2008 Aug 16;372(9638):547-53.

ONTARGET Investigators; Yusuf S, Teo KK, Pogue J, Dyal L, Copland I, Schumacher H, Dagenais G, Sleight P, Anderson C. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med. 2008 Apr 10;358(15):1547-59. Epub 2008 Mar 31.

Held C, Gerstein HC, Yusuf S, Zhao F, Hilbrich L, Anderson C, Sleight P, Teo K; ONTARGET/TRANSCEND Investigators. Glucose levels predict hospitalization for congestive heart failure in patients at high cardiovascular risk. Circulation. 2007 Mar 20;115(11):1371-5. Epub 2007 Mar 5.

Responsible Party:	Boehringer Ingelheim ( Boehringer Ingelheim, Study Chair )
Study ID Numbers:	502.373
Study First Received:	September 9, 2005
Results First Received:	June 15, 2009
Last Updated:	September 18, 2009
ClinicalTrials.gov Identifier:	NCT00153101 History of Changes
Health Authority:	Argentina: National Administration of Medicines, Food and Medical Technology; Australia: Responsilble Ethics Committee; Austria: Ministry for Social Security and Generations; Belgium: Federal Agency for Medicines and Health Products; Brazil: National Health Surveillance Agency; Canada: Health Canada; China: State Food and Drug Administration; Czech Republic: State Institute for Drug Control (SUKL); Denmark: Danish Medicines Agency; Finland: Finnish Medicines Agency; France: AFFSAPS; Germany: Federal Institute for Drugs and Medical Devices; Great Britain: MHRA; Greece: HELLENIC REPUBLIC MINISTRY OF HEALTH AND WELFARE NATIONAL ORGANISATION OF MEDICINES (EOF); Hong Kong: Dept. of Health, Hong Kong; Hungary: National Institute of Pharmacy (OGYI), H-1051 Budapest; Ireland: The Irish Medicines Board; Italy: Comitato Etico delle Aziende Sanitarie della Regione Umbria; Korea, Republic of: Korea Food and Drug Administration (KFDA); Malaysia: Drug Control Authority; Mexico: Comision Federal para la Proteccion contra Riesgos Sanitarios (COFEPRIS); Netherlands: The Central Committee on Research Involving Human Subjects (CCMO); New Zealand: Multicentre Ethics Committee/Medsafe; Norway: Norwegian Medicines Agency (Statens Legemiddelverk); Philippines: Bureau of Pharmaceutical Affairs, Department of Health; Poland: CEBK, Warsaw; Portugal: INFARMED - National Authority of Medicines and Health Products, IP; Russia: Ministry of Health and Social Development of the Russian Federation; Singapore: Centre of Drug Administration; Slovakia: SUKL (state institute for drug control), SK-825 08 Bratislava 26; South Africa: Medicines Control Council; Spain: Ministry of Health; Sweden: Medical Product Agency; Switzerland: Swissmedic Schweizerisches Heilmittelinstitut (Swiss Agency for Therapeutic Products); Taiwan: Dept. of Health, Executive Yuan, Taiwan; Thailand: Bureau of Pharmaceutical Affairs, Department of Health; Turkey: Ministry of Health Central Ethics Committee; Ukraine: State Pharmacology Centre of the Ministry of Health of Ukraine; United Arab. Emirates: Medical Affairs Department of Health and Medical Services, General Authority Health Services, Ministry of Health for Northern Emirates; United States: Food and Drug Administration