A Randomized Controlled Trial of Aliskiren in the Prevention of Major Cardiovascular Events in Elderly People (APOLLO)

This study has been terminated.

(Terminated early in agreement with Health Authorities for feasibility reasons)

Sponsor:

Information provided by (Responsible Party):

Novartis ( Novartis Pharmaceuticals )

ClinicalTrials.gov Identifier:

NCT01259297

First received: December 10, 2010

Last updated: February 27, 2014

Last verified: February 2014

History of Changes

Results First Received: December 18, 2013

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Factorial Assignment; Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition:	Cardiovascular Events
Interventions:	Drug: Aliskiren Drug: Amlodipine Drug: Hydrochlorothiazide (HCTZ) Drug: Placebo for Aliskiren Drug: Placebo for Amlodipine Drug: Placebo for Hydrochlorothiazide (HCTZ)

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups

	Description
Aliskiren + Hydrochlorothiazide (HCTZ)	In run-in period (4-5 weeks) , patients on CCB background therapy and approximately 50% of patients on neither thiazide nor CCB background therapy: received hydrochlorothiazide 12.5/25 mg and Aliskiren 150/300 mg daily in a titrated manner as per protocol. In double blind period, all patients who successfully completed run-in with HCTZ plus aliskiren were randomized equally to the 4 arms of the HCTZ add-on stratum. Patients randomized to this arm received Aliskiren 300 mg + HCTZ 25 mg once daily.
Aliskiren + Placebo for HCTZ	In double blind period, all patients who successfully completed run-in with HCTZ plus Aliskiren were randomized equally to the 4 arms of the HCTZ add-on stratum. In double blind period, randomized patients to this arm received Aliskiren 300 mg + placebo for HCTZ 25 mg once daily
Aliskiren + Amlodipine	In run-in period (4-5 weeks) , patients on thiazide background therapy and approximately 50% of patients on neither CCB nor thiazide background therapy received Amlodipine 5 mg and Aliskiren 150/300 mg daily in a titrated manner as per protocol. In double blind period, patients who successfully completed run-in with Amlodipine plus Aliskiren were randomized equally to the 4 arms of the Amlodipine add-on stratum. Patients randomized to this arm received Aliskiren 300 mg + Amlodipine 5 mg once daily during the double blind period.
Aliskiren + Placebo for Amlodipine	In double blind period, all patients who successfully completed run-in with Amlodipine plus aliskiren were randomized equally to the 4 arms of the Amlodipine add-on stratum. In double blind period, randomized patients to this arm received Aliskiren 300 mg + placebo for Amlodipine 5 mg
HCTZ + Placebo for Aliskiren	In double blind period, all patients who successfully completed run-in with HCTZ plus Aliskiren were randomized equally to the 4 arms of the HCTZ add-on stratum. In double blind period, randomized patients to this arm received HCTZ 25 mg + placebo for Aliskiren 300 mg once daily
Placebo for Aliskiren + Placebo for HCTZ	In double blind period, all patients who successfully completed run-in with HCTZ plus aliskiren were randomized equally to the 4 arms of the HCTZ add-on stratum. In double blind period, randomized patients to this arm received placebo for Aliskiren 300 mg + placebo for HCTZ 25 mg once daily
Amlodipine + Placebo for Aliskiren	In double blind period, all patients who successfully completed run-in with Amlodipine plus Aliskiren were randomized equally to the 4 arms of the Amlodipine add-on stratum. In double blind period, randomized patients to this arm received Amlodipine 5 mg + placebo for Aliskiren 300 mg once daily
Placebo for Aliskiren + Placebo for Amlodipine	In double blind period, all patients who successfully completed run-in with Amlodipine plus Aliskiren were randomized equally to the 4 arms of the Amlodipine add-on stratum. In double blind period, randomized patients to this arm received placebo for Aliskiren 300 mg + placebo for Amlodipine 5 mg once daily

Participant Flow for 2 periods

Period 1: Run-in Open Label Period (4-5 Weeks)

	Aliskiren + Hydrochlorothiazide (HCTZ)	Aliskiren + Amlodipine
STARTED	1335	1001
COMPLETED	980	779
NOT COMPLETED	355	222

Period 2: Double Blind Randomized Period

	Aliskiren + Hydrochlorothiazide (HCTZ)	Aliskiren + Placebo for HCTZ	Aliskiren + Amlodipine	Aliskiren + Placebo for Amlodipine	HCTZ + Placebo for Aliskiren	Placebo for Aliskiren + Placebo for HCTZ	Amlodipine + Placebo for Aliskiren	Placebo for Aliskiren + Placebo for Amlodipine
STARTED	244	232	189	195	251	253	196	199
COMPLETED	242	229	188	191	247	245	190	196
NOT COMPLETED	2	3	1	4	4	8	6	3
Death	1	1	1	2	1	5	2	1
Withdrew informed consent/ refused visit	1	1	0	2	2	1	1	1
Other reasons	0	1	0	0	1	2	3	1

Baseline Characteristics

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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.
Full analysis Set (FAS): All randomized patients, regardless of receiving study medication.

Reporting Groups

	Description
Aliskiren + Hydrochlorothiazide (HCTZ)	In double blind period, all patients who successfully completed run-in with HCTZ plus Aliskiren were randomized equally to the 4 arms of the HCTZ add-on stratum. Patients randomized to this arm received Aliskiren 300 mg + HCTZ 25 mg once daily.
Aliskiren + Placebo for HCTZ	In double blind period, all patients who successfully completed run-in with HCTZ plus Aliskiren were randomized equally to the 4 arms of the HCTZ add-on stratum. In double blind period, randomized patients to this arm received Aliskiren 300 mg + placebo for HCTZ 25 mg once daily
Aliskiren + Amlodipine	In double blind period, all patients who successfully completed run-in with Amlodipine plus Aliskiren were randomized equally to the 4 arms of the Amlodipine add-on stratum. Patients randomized to this arm received Aliskiren 300 mg + Amlodipine 5 mg once daily during the double blind period.
Aliskiren + Placebo for Amlodipine	In double blind period, all patients who successfully completed run-in with Amlodipine plus Aliskiren were randomized equally to the 4 arms of the Amlodipine add-on stratum. In double blind period, randomized patients to this arm received Aliskiren 300 mg + placebo for Amlodipine 5 mg
HCTZ + Placebo for Aliskiren	In double blind period, all patients who successfully completed run-in with HCTZ plus Aliskiren were randomized equally to the 4 arms of the HCTZ add-on stratum. In double blind period, randomized patients to this arm received HCTZ 25 mg + placebo for Aliskiren 300 mg once daily
Placebo for Aliskiren + Placebo for HCTZ	In double blind period, all patients who successfully completed run-in with HCTZ plus Aliskiren were randomized equally to the 4 arms of the HCTZ add-on stratum. In double blind period, randomized patients to this arm received placebo for Aliskiren 300 mg + placebo for HCTZ 25 mg once daily
Amlodipine + Placebo for Aliskiren	In double blind period, all patients who successfully completed run-in with Amlodipine plus Aliskiren were run-in stratum randomized equally to the 4 arms of the Amlodipine add-on stratum. In double blind period, randomized patients to this arm received Amlodipine 5 mg + placebo for Aliskiren 300 mg once daily
Placebo for Aliskiren + Placebo for Amlodipine	In double blind period, all patients who successfully completed run-in with Amlodipine plus Aliskiren were randomized equally to the 4 arms of the Amlodipine add-on stratum. In double blind period, randomized patients to this arm received placebo for Aliskiren 300 mg + placebo for Amlodipine 5 mg once daily
Total	Total of all reporting groups

Baseline Measures

	Aliskiren + Hydrochlorothiazide (HCTZ)	Aliskiren + Placebo for HCTZ	Aliskiren + Amlodipine	Aliskiren + Placebo for Amlodipine	HCTZ + Placebo for Aliskiren	Placebo for Aliskiren + Placebo for HCTZ	Amlodipine + Placebo for Aliskiren	Placebo for Aliskiren + Placebo for Amlodipine	Total
Number of Participants [units: participants]	244	232	189	195	251	253	196	199	1759
Age, Customized [units: participants]
>=65 to <75 years	165	174	127	125	180	189	135	134	1229
>=75 years	79	58	62	70	71	64	61	65	530
Gender [units: participants]
Female	119	109	91	89	122	108	87	88	813
Male	125	123	98	106	129	145	109	111	946

Outcome Measures

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1. Primary:

Number of Participants With Composite Cardiovascular Endpoints in Aliskiren Based Regimen Versus Non-Aliskiren Based Regimen [ Time Frame: End of study (209 days (median)) ]

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2. Primary:

Number of Participants With Composite Cardiovascular Endpoints in Aliskiren+Amlodipine/HCTZ Group Versus All Placebo Group [ Time Frame: End of study (209 days (median)) ]

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3. Secondary:

Change From Baseline to End of Study in Standard Assessment of Global Activities in the Elderly (SAGE) Dimensions (Part I) [ Time Frame: Baseline, End of study (209 days [median]) ]

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4. Secondary:

Percentage of Participants With Standard Assessment of Global Activities in the Elderly (SAGE) Dimensions (Part II) [ Time Frame: End of study (209 days [median]) ]

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5. Secondary:

Number of Participants With Renal Dysfunction in Aliskiren Based Regimen Versus Non-Aliskiren Based Regimen [ Time Frame: End of study (209 days (median)) ]

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6. Secondary:

Number of Participants With Total Mortality in Aliskiren Based Regimen Versus Non-aliskiren Based Regimen [ Time Frame: End of study (209 days (median)) ]

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7. Other Pre-specified:

Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) [ Time Frame: Baseline (BL), 6 week, 6 month and 12 month ]

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8. Other Pre-specified:

Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) [ Time Frame: Baseline (BL), 6 week, 6 month and 12 month ]

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Serious Adverse Events

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Other Adverse Events

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Limitations and Caveats

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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
Due to early termination, 1759 patients were randomized as against 11,000. Only 25 primary endpoints had accrued during median follow-up of 209 days as against planned 2000 in 5 years. These low numbers significantly limit interpretation of results.

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: The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.

Results Point of Contact:

Name/Title: Study Director
Organization: Novartis Pharmaceuticals
phone: 862-778-8300
e-mail: trialandresults.registries@novartis.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Teo KK, Pfeffer M, Mancia G, O'Donnell M, Dagenais G, Diaz R, Dans A, Liu L, Bosch J, Joseph P, Copland I, Jung H, Pogue J, Yusuf S; Aliskiren Prevention of Later Life Outcomes trial Investigators. Aliskiren alone or with other antihypertensives in the elderly with borderline and stage 1 hypertension: the APOLLO trial. Eur Heart J. 2014 Jul;35(26):1743-51. doi: 10.1093/eurheartj/ehu079. Epub 2014 Mar 9.

Responsible Party:	Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:	NCT01259297 History of Changes
Other Study ID Numbers:	CSPP100G2301 2009-010170-38 ( EudraCT Number )
Study First Received:	December 10, 2010
Results First Received:	December 18, 2013
Last Updated:	February 27, 2014
Health Authority:	United States: Food and Drug Administration Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica Brazil: Ministry of Health Canada: Health Canada Chile: Ministry of Health China: Food and Drug Administration Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos Czech Republic: State Institute for Drug Control Germany: Federal Institute for Drugs and Medical Devices Hungary: National Institute of Pharmacy India: Central Drugs Standard Control Organization Ireland: Ministry of Health Israel: Ministry of Health Italy: National Institute of Health Malaysia: Ministry of Health Netherlands: Medicines Evaluation Board (MEB) Philippines: Bureau of Food and Drugs (BFAD) Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products Russia: Ministry of Health of the Russian Federation South Africa: Medicines Control Council Spain: Spanish Agency of Medicines Sweden: Medical Products Agency Turkey: Ministry of Health

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