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3A: Registry for Ambulant Therapy With RAS-Inhibitors in Hypertension-patients in Germany

Sponsor
Stiftung Institut fuer Herzinfarktforschung (Other)
Overall Status
Completed
CT.gov ID
NCT01454583
Collaborator
Novartis Pharmaceuticals (Industry)
15,337
Enrollment
45
Duration (Months)

Study Details

Study Description

Brief Summary

In Germany nearly half of the population present elevated values of blood pressure, with - as a result of lifestyle factors and a growing average age - further increasing numbers.

Consequences of arterial hypertension may be cardiovascular diseases, cerebrovascular events, and renal insufficiency. Thus, hypertension therapy focuses on the reduction of these complications.

The aims of the 3A-registry are the characterization of outpatients with hypertension, their diagnostic procedures and medical treatment (esp. with renin inhibitors), therapy compliance and success, clinical events, and an assessment of overall guideline adherence in the treatment of these patients.

Patients fulfilling the relevant criteria are enrolled and followed up by their general practitioner or medical specialist.

Condition or Disease Intervention/Treatment Phase

Study Design

Study Type:
Observational
Actual Enrollment :
15337 participants
Observational Model:
Case-Only
Time Perspective:
Prospective
Official Title:
3A-Register Zur Ambulanten Therapie Mit RAS-Inhibitoren in Patienten Mit Arterieller Hypertonie in Deutschland
Study Start Date :
Oct 1, 2008
Actual Primary Completion Date :
Oct 1, 2009
Actual Study Completion Date :
Jul 1, 2012

Arms and Interventions

Arm Intervention/Treatment
Aliskiren

Patients getting Aliskiren at baseline

Drug: Aliskiren
Aliskiren (Rasilez®, Novartis) is the first clinically available substance with direct renin inhibition (DRI) which effectively lowers blood pressure.
Other Names:
  • Rasilez

    		•
    ACE-I/ARB

    Patients getting ACE-I (angiotensin-converting enzyme inhibitors) or ARB (angiotensin-receptor blockers) at baseline, but not Aliskiren

    Drug: ACE-I/ARB
    No RAS-inhibition

    Patients getting no drugs at baseline that inhibit the renin-angiotensin-aldosterone-system (RAAS)

    Drug: No RAS-inhibition

    Outcome Measures

    Primary Outcome Measures

    1. Efficacy of Hypertension Treatment on Systolic Blood Pressure (SBP) [baseline and 1 year]

      Relative change of systolic office blood pressure since baseline, i.e. SBP at baseline minus SBP after 1 year, the difference divided by the baseline value, multiplied by 100

    2. Efficacy of Hypertension Treatment on Diastolic Blood Pressure (DBP) [Baseline and 1 year]

      Relative change of diastolic office blood pressure since baseline, i.e. DBP at baseline minus DBP after 1 year, the difference divided by the baseline value, multiplied by 100

    3. Efficacy of Hypertension Treatment on Systolic Blood Pressure (SBP) [Baseline and 2 years]

      Relative change of systolic office blood pressure since baseline, i.e. SBP at baseline minus SBP after 2 years, the difference divided by the baseline value, multiplied by 100

    4. Efficacy of Hypertension Treatment on Diastolic Office Blood Pressure (DBP) [Baseline and 2 years]

      Relative change of diastolic office blood pressure since baseline, i.e. DBP at baseline minus DBP after 1 year, the difference divided by the baseline value, multiplied by 100

    5. Efficacy of Hypertension Treatment on Systolic Blood Pressure (SBP) [Baseline and 3 years]

      Relative change of systolic office blood pressure since baseline, i.e. SBP at baseline minus SBP after 3 years, the difference divided by the baseline value, multiplied by 100

    6. Efficacy of Hypertension Treatment on Diastolic Blood Pressure (DBP) [Baseline and 3 years]

      Relative change of diastolic office blood pressure since baseline, i.e. DBP at baseline minus DBP after 3 years, the difference divided by the baseline value, multiplied by 100

    Secondary Outcome Measures

    1. Therapy Adherence Regarding Drug Treatment [Baseline and 1 year]

      Percentage of patients not having changed the therapy group after 1 year (DRI, ARB/ACE-I, or No-RAS-I, referring to their therapy at baseline)

    2. Therapy Adherence Regarding Drug Treatment [Baseline and 2 years]

      Percentage of patients not having changed the therapy group after 2 years (DRI, ARB/ACE-I, or No-RAS-I, referring to their therapy at baseline)

    3. Therapy Adherence Regarding Drug Treatment [Baseline and 3 years]

      Percentage of patients not having changed the therapy group after 3 years (DRI, ARB/ACE-I, or No-RAS-I, referring to their therapy at baseline)

    4. Adverse Events [1 year follow up]

      Percentage of participants that experienced at least one adverse event during the first year of observation period

    5. Adverse Events [2 years follow up]

      Percentage of participants that experienced at least one adverse event during the first two years of observation period

    6. Adverse Events [3 years follow up]

      Percentage of participants that experienced at least one adverse event during the three years of observation period

    7. Therapeutic Success of Hypertension Treatment on Systolic Blood Pressure (SBP) as Measured by 24-hour Blood Pressure Measurement [Baseline and 1 year]

      Relative change of ambulatory, systolic 24h BP means since baseline, i.e. 24h SBP means at baseline minus corresponding means after 1 year, the differences divided by the baseline value, multiplied by 100. Mean SBP of a patient was calculated as the arithmetic mean of automatically recorded SBP values over a contiguous period of 24 h.

    8. Therapeutic Success of Hypertension Treatment on Diastolic Blood Pressure (DBP) as Measured by 24-hour Blood Pressure Measurement [Baseline and 1 year]

      Relative change of ambulatory, diastolic 24h BP means since baseline, i.e. 24h DBP means at baseline minus corresponding means after 1 year, the differences divided by the baseline value, multiplied by 100. Mean DBP of a patient was calculated as the arithmetic mean of automatically recorded DBP values over a contiguous period of 24 h.

    9. Therapeutic Success of Hypertension Treatment on Systolic Blood Pressure (SBP) as Measured by 24-hour Blood Pressure Measurement [Baseline and 2 years]

      Relative change of ambulatory, systolic 24h BP means since baseline, i.e. 24h SBP means at baseline minus corresponding means after 2 years, the differences divided by the baseline value, multiplied by 100. Mean SBP of a patient was calculated as the arithmetic mean of automatically recorded SBP values over a contiguous period of 24 h.

    10. Therapeutic Success of Hypertension Treatment on Diastolic Blood Pressure (DBP) as Measured by 24-hour Blood Pressure Measurement [Baseline and 2 years]

      Relative change of ambulatory, diastolic 24h BP means since baseline, i.e. 24h DBP means at baseline minus corresponding means after 2 years, the differences divided by the baseline value, multiplied by 100. Mean DBP of a patient was calculated as the arithmetic mean of automatically recorded DBP values over a contiguous period of 24 h.

    11. Therapeutic Success of Hypertension Treatment on Systolic Blood Pressure (SBP) as Measured by 24-hour Blood Pressure Measurement [Baseline and 3 years]

      Relative change of ambulatory, systolic 24h BP means since baseline, i.e. 24h SBP means at baseline minus corresponding means after 3 years, the differences divided by the baseline value, multiplied by 100. Mean SBP of a patient was calculated as the arithmetic mean of automatically recorded SBP values over a contiguous period of 24 h.

    12. Therapeutic Success of Hypertension Treatment on Diastolic Blood Pressure (DBP) as Measured by 24-hour Blood Pressure Measurement [Baseline and 3 years]

      Relative change of ambulatory, diastolic 24h BP means since baseline, i.e. 24h DBP means at baseline minus corresponding means after 3 years, the differences divided by the baseline value, multiplied by 100. Mean DBP of a patient was calculated as the arithmetic mean of automatically recorded DBP values over a contiguous period of 24 h.

    13. Influence of Anti-hypertensive Treatment on Renal Function [1 year follow up]

      Improvement of the estimated glomerular filtration rate (eGFR, using the CKD-EPI equation) by more than 2.5ml/min/1.73m², compared to baseline

    14. Influence of Anti-hypertensive Treatment on Renal Function [2 years follow up]

      Improvement of the estimated glomerular filtration rate (eGFR, using the CKD-EPI equation) by more than 2.5ml/min/1.73m², compared to baseline

    15. Influence of Anti-hypertensive Treatment on Renal Function [3 years follow up]

      Improvement of the estimated glomerular filtration rate (eGFR, using the CKD-EPI equation) by more than 2.5ml/min/1.73m², compared to baseline

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • treatment as outpatient

    • arterial hypertension

    • treatment with a renin inhibitor, ACE inhibitor, ARB, or without RAS blockade

    • informed consent

    Exclusion Criteria:
    • foreseeable difficulties to perform follow up

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Stiftung Institut fuer Herzinfarktforschung
    • Novartis Pharmaceuticals

    Investigators

    • Study Chair: Uwe Zeymer, M.D., Stiftung Institut für Herzinfarktforschung

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Stiftung Institut fuer Herzinfarktforschung
    ClinicalTrials.gov Identifier:
    NCT01454583
    Other Study ID Numbers:
    • 3A-Registry
    First Posted:
    Oct 19, 2011
    Last Update Posted:
    Jul 21, 2016
    Last Verified:
    Jun 1, 2016
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Keywords provided by Stiftung Institut fuer Herzinfarktforschung
    renin inhibitor
    ACE inhibitor
    ARB (AT1 receptor blockers)
    RAS blockade
    Additional relevant MeSH terms:
    Hypertension

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Aliskiren ACE-I/ARB No RAS-inhibition
    Arm/Group Description Patients treated with Aliskiren (DRI) at baseline. In the 3rd year period, only patients with Diabetes Mellitus (DM) or Heart Failure (HF) were considered. Patients treated with ACE-I or ARB (ARB/ACE-I) at baseline. In the 3rd year period, only patients with Diabetes Mellitus (DM) or Heart Failure (HF) were considered. Patients treated with no RAS-inhibition drugs at baseline. In the 3rd year period, only patients with Diabetes Mellitus (DM) or Heart Failure (HF) were considered.
    Period Title: 1st Year
    STARTED 10177 2696 2113
    COMPLETED 9120 2378 1933
    NOT COMPLETED 1057 318 180
    Period Title: 1st Year
    STARTED 10177 2696 2113
    COMPLETED 6212 1647 1376
    NOT COMPLETED 3965 1049 737
    Period Title: 1st Year
    STARTED 3791 982 582
    COMPLETED 1832 470 285
    NOT COMPLETED 1959 512 297

    Baseline Characteristics

    Arm/Group Title Group A Group B Group C Total
    Arm/Group Description Patients treated with Aliskiren (DRI) Patients treated with ACE-I or ARB (ARB/ACE-I) Patients without any RAS inhibition (No-RAS-I) Total of all reporting groups
    Overall Participants 10177 2696 2113 14986
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    5109
    50.2%
    1300
    48.2%
    1181
    55.9%
    7590
    50.6%
    >=65 years
    5068
    49.8%
    1396
    51.8%
    932
    44.1%
    7396
    49.4%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    63.6
    (12.06)
    63.7
    (11.92)
    61.3
    (13.36)
    63.3
    (12.26)
    Sex: Female, Male (Count of Participants)
    Female
    4658
    45.8%
    1229
    45.6%
    1085
    51.3%
    6972
    46.5%
    Male
    5519
    54.2%
    1467
    54.4%
    1028
    48.7%
    8014
    53.5%

    Outcome Measures

    1. Primary Outcome
    Title Efficacy of Hypertension Treatment on Systolic Blood Pressure (SBP)
    Description Relative change of systolic office blood pressure since baseline, i.e. SBP at baseline minus SBP after 1 year, the difference divided by the baseline value, multiplied by 100
    Time Frame baseline and 1 year

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Group A Group B Group C
    Arm/Group Description Patients treated with Aliskiren (DRI) Patients treated with ACE-I or ARB (ARB/ACE-I) Patients without any RAS inhibition (No-RAS-I)
    Measure Participants 8880 2321 1896
    Mean (Standard Deviation) [percent change]
    11.8
    (12.5)
    9.7
    (12.4)
    9.9
    (12.8)
    2. Secondary Outcome
    Title Therapy Adherence Regarding Drug Treatment
    Description Percentage of patients not having changed the therapy group after 1 year (DRI, ARB/ACE-I, or No-RAS-I, referring to their therapy at baseline)
    Time Frame Baseline and 1 year

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Group A Group B Group C
    Arm/Group Description Patients treated with Aliskiren (DRI) Patients treated with ACE-I or ARB (ARB/ACE-I) Patients without any RAS inhibition (No-RAS-I)
    Measure Participants 9120 2378 1933
    Number [percentage of patients]
    92.8
    94.9
    85.0
    3. Secondary Outcome
    Title Therapy Adherence Regarding Drug Treatment
    Description Percentage of patients not having changed the therapy group after 2 years (DRI, ARB/ACE-I, or No-RAS-I, referring to their therapy at baseline)
    Time Frame Baseline and 2 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Group A Group B Group C
    Arm/Group Description Patients treated with Aliskiren (DRI) Patients treated with ACE-I or ARB (ARB/ACE-I) Patients without any RAS inhibition (No-RAS-I)
    Measure Participants 6212 1647 1376
    Number [percentage of patients]
    85.2
    89.7
    72.5
    4. Secondary Outcome
    Title Therapy Adherence Regarding Drug Treatment
    Description Percentage of patients not having changed the therapy group after 3 years (DRI, ARB/ACE-I, or No-RAS-I, referring to their therapy at baseline)
    Time Frame Baseline and 3 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Group A Group B Group C
    Arm/Group Description Patients treated with Aliskiren (DRI) Patients treated with ACE-I or ARB (ARB/ACE-I) Patients without any RAS inhibition (No-RAS-I)
    Measure Participants 1832 470 285
    Number [percentage of patients]
    65.8
    82.1
    60.7
    5. Secondary Outcome
    Title Adverse Events
    Description Percentage of participants that experienced at least one adverse event during the first year of observation period
    Time Frame 1 year follow up

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Group A Group B Group C
    Arm/Group Description Patients treated with Aliskiren (DRI) Patients treated with ACE-I or ARB (ARB/ACE-I) Patients without any RAS inhibition (No-RAS-I)
    Measure Participants 10177 2696 2113
    Number [percentage of patients]
    5.3
    4.1
    3.4
    6. Secondary Outcome
    Title Adverse Events
    Description Percentage of participants that experienced at least one adverse event during the first two years of observation period
    Time Frame 2 years follow up

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Group A Group B Group C
    Arm/Group Description Patients treated with Aliskiren (DRI) Patients treated with ACE-I or ARB (ARB/ACE-I) Patients without any RAS inhibition (No-RAS-I)
    Measure Participants 10177 2696 2113
    Number [percentage of patients]
    7.2
    6.6
    5.3
    7. Secondary Outcome
    Title Adverse Events
    Description Percentage of participants that experienced at least one adverse event during the three years of observation period
    Time Frame 3 years follow up

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Group A Group B Group C
    Arm/Group Description Patients treated with Aliskiren (DRI) Patients treated with ACE-I or ARB (ARB/ACE-I) Patients without any RAS inhibition (No-RAS-I)
    Measure Participants 3791 982 582
    Number [percentage of patients]
    12.9
    12.6
    9.5
    8. Secondary Outcome
    Title Therapeutic Success of Hypertension Treatment on Systolic Blood Pressure (SBP) as Measured by 24-hour Blood Pressure Measurement
    Description Relative change of ambulatory, systolic 24h BP means since baseline, i.e. 24h SBP means at baseline minus corresponding means after 1 year, the differences divided by the baseline value, multiplied by 100. Mean SBP of a patient was calculated as the arithmetic mean of automatically recorded SBP values over a contiguous period of 24 h.
    Time Frame Baseline and 1 year

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Group A Group B Group C
    Arm/Group Description Patients treated with Aliskiren (DRI) Patients treated with ACE-I or ARB (ARB/ACE-I) Patients without any RAS inhibition (No-RAS-I)
    Measure Participants 2015 532 358
    Mean (Standard Deviation) [percent change]
    7.0
    (10.0)
    5.9
    (10.0)
    5.3
    (8.6)
    9. Secondary Outcome
    Title Therapeutic Success of Hypertension Treatment on Diastolic Blood Pressure (DBP) as Measured by 24-hour Blood Pressure Measurement
    Description Relative change of ambulatory, diastolic 24h BP means since baseline, i.e. 24h DBP means at baseline minus corresponding means after 1 year, the differences divided by the baseline value, multiplied by 100. Mean DBP of a patient was calculated as the arithmetic mean of automatically recorded DBP values over a contiguous period of 24 h.
    Time Frame Baseline and 1 year

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Group A Group B Group C
    Arm/Group Description Patients treated with Aliskiren (DRI) Patients treated with ACE-I or ARB (ARB/ACE-I) Patients without any RAS inhibition (No-RAS-I)
    Measure Participants 2015 532 358
    Mean (Standard Deviation) [percent change]
    6.5
    (11.9)
    5.2
    (11.4)
    5.9
    (10.1)
    10. Secondary Outcome
    Title Therapeutic Success of Hypertension Treatment on Systolic Blood Pressure (SBP) as Measured by 24-hour Blood Pressure Measurement
    Description Relative change of ambulatory, systolic 24h BP means since baseline, i.e. 24h SBP means at baseline minus corresponding means after 2 years, the differences divided by the baseline value, multiplied by 100. Mean SBP of a patient was calculated as the arithmetic mean of automatically recorded SBP values over a contiguous period of 24 h.
    Time Frame Baseline and 2 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Group A Group B Group C
    Arm/Group Description Patients treated with Aliskiren (DRI) Patients treated with ACE-I or ARB (ARB/ACE-I) Patients without any RAS inhibition (No-RAS-I)
    Measure Participants 988 237 186
    Mean (Standard Deviation) [percent change]
    8.3
    (10.7)
    6.6
    (11.1)
    7.2
    (9.1)
    11. Secondary Outcome
    Title Therapeutic Success of Hypertension Treatment on Diastolic Blood Pressure (DBP) as Measured by 24-hour Blood Pressure Measurement
    Description Relative change of ambulatory, diastolic 24h BP means since baseline, i.e. 24h DBP means at baseline minus corresponding means after 2 years, the differences divided by the baseline value, multiplied by 100. Mean DBP of a patient was calculated as the arithmetic mean of automatically recorded DBP values over a contiguous period of 24 h.
    Time Frame Baseline and 2 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Group A Group B Group C
    Arm/Group Description Patients treated with Aliskiren (DRI) Patients treated with ACE-I or ARB (ARB/ACE-I) Patients without any RAS inhibition (No-RAS-I)
    Measure Participants 988 237 186
    Mean (Standard Deviation) [percent change]
    7.7
    (12.0)
    5.6
    (14.6)
    6.7
    (11.2)
    12. Primary Outcome
    Title Efficacy of Hypertension Treatment on Diastolic Blood Pressure (DBP)
    Description Relative change of diastolic office blood pressure since baseline, i.e. DBP at baseline minus DBP after 1 year, the difference divided by the baseline value, multiplied by 100
    Time Frame Baseline and 1 year

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Group A Group B Group C
    Arm/Group Description Patients treated with Aliskiren (DRI) Patients treated with ACE-I or ARB (ARB/ACE-I) Patients without any RAS inhibition (No-RAS-I)
    Measure Participants 8880 2321 1896
    Mean (Standard Deviation) [percent change]
    8.9
    (13.0)
    7.7
    (12.9)
    8.0
    (13.5)
    13. Primary Outcome
    Title Efficacy of Hypertension Treatment on Systolic Blood Pressure (SBP)
    Description Relative change of systolic office blood pressure since baseline, i.e. SBP at baseline minus SBP after 2 years, the difference divided by the baseline value, multiplied by 100
    Time Frame Baseline and 2 years

    Outcome Measure Data

    Analysis Population Description
    Patients with RR measurement at baseline and 2 years follow-up
    Arm/Group Title Group A Group B Group C
    Arm/Group Description Patients treated with Aliskiren (DRI) Patients treated with ACE-I or ARB (ARB/ACE-I) Patients without any RAS inhibition (No-RAS-I)
    Measure Participants 6055 1610 1345
    Mean (Standard Deviation) [percent change]
    12.8
    (12.9)
    10.0
    (13.5)
    10.4
    (12.7)
    14. Primary Outcome
    Title Efficacy of Hypertension Treatment on Diastolic Office Blood Pressure (DBP)
    Description Relative change of diastolic office blood pressure since baseline, i.e. DBP at baseline minus DBP after 1 year, the difference divided by the baseline value, multiplied by 100
    Time Frame Baseline and 2 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Group A Group B Group C
    Arm/Group Description Patients treated with Aliskiren (DRI) Patients treated with ACE-I or ARB (ARB/ACE-I) Patients without any RAS inhibition (No-RAS-I)
    Measure Participants 6054 1609 1345
    Mean (Standard Deviation) [percent change]
    10.3
    (13.0)
    8.5
    (13.5)
    8.9
    (13.4)
    15. Primary Outcome
    Title Efficacy of Hypertension Treatment on Systolic Blood Pressure (SBP)
    Description Relative change of systolic office blood pressure since baseline, i.e. SBP at baseline minus SBP after 3 years, the difference divided by the baseline value, multiplied by 100
    Time Frame Baseline and 3 years

    Outcome Measure Data

    Analysis Population Description
    Patients with DM or HF and RR measurement at baseline and 3 years follow-up
    Arm/Group Title Group A Group B Group C
    Arm/Group Description Patients treated with Aliskiren (DRI) Patients treated with ACE-I or ARB (ARB/ACE-I) Patients without any RAS inhibition (No-RAS-I)
    Measure Participants 1700 433 264
    Mean (Standard Deviation) [percent change]
    12.0
    (13.4)
    8.9
    (14.2)
    9.4
    (13.1)
    16. Primary Outcome
    Title Efficacy of Hypertension Treatment on Diastolic Blood Pressure (DBP)
    Description Relative change of diastolic office blood pressure since baseline, i.e. DBP at baseline minus DBP after 3 years, the difference divided by the baseline value, multiplied by 100
    Time Frame Baseline and 3 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Group A Group B Group C
    Arm/Group Description Patients treated with Aliskiren (DRI) Patients treated with ACE-I or ARB (ARB/ACE-I) Patients without any RAS inhibition (No-RAS-I)
    Measure Participants 1700 433 264
    Mean (Standard Deviation) [percent change]
    9.1
    (13.6)
    6.2
    (14.2)
    6.4
    (14.2)
    17. Secondary Outcome
    Title Therapeutic Success of Hypertension Treatment on Systolic Blood Pressure (SBP) as Measured by 24-hour Blood Pressure Measurement
    Description Relative change of ambulatory, systolic 24h BP means since baseline, i.e. 24h SBP means at baseline minus corresponding means after 3 years, the differences divided by the baseline value, multiplied by 100. Mean SBP of a patient was calculated as the arithmetic mean of automatically recorded SBP values over a contiguous period of 24 h.
    Time Frame Baseline and 3 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Group A Group B Group C
    Arm/Group Description Patients treated with Aliskiren (DRI) Patients treated with ACE-I or ARB (ARB/ACE-I) Patients without any RAS inhibition (No-RAS-I)
    Measure Participants 279 51 31
    Mean (Standard Deviation) [percent change]
    7.9
    (12.4)
    6.1
    (11.2)
    7.3
    (11.8)
    18. Secondary Outcome
    Title Therapeutic Success of Hypertension Treatment on Diastolic Blood Pressure (DBP) as Measured by 24-hour Blood Pressure Measurement
    Description Relative change of ambulatory, diastolic 24h BP means since baseline, i.e. 24h DBP means at baseline minus corresponding means after 3 years, the differences divided by the baseline value, multiplied by 100. Mean DBP of a patient was calculated as the arithmetic mean of automatically recorded DBP values over a contiguous period of 24 h.
    Time Frame Baseline and 3 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Group A Group B Group C
    Arm/Group Description Patients treated with Aliskiren (DRI) Patients treated with ACE-I or ARB (ARB/ACE-I) Patients without any RAS inhibition (No-RAS-I)
    Measure Participants 279 51 31
    Mean (Standard Deviation) [percent change]
    5.4
    (14.8)
    5.3
    (12.4)
    6.4
    (11.4)
    19. Secondary Outcome
    Title Influence of Anti-hypertensive Treatment on Renal Function
    Description Improvement of the estimated glomerular filtration rate (eGFR, using the CKD-EPI equation) by more than 2.5ml/min/1.73m², compared to baseline
    Time Frame 1 year follow up

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Group A Group B Group C
    Arm/Group Description Patients treated with Aliskiren (DRI) Patients treated with ACE-I or ARB (ARB/ACE-I) Patients without any RAS inhibition (No-RAS-I)
    Measure Participants 8884 2302 1893
    Number [percentage of patients]
    33.5
    32.1
    34.1
    20. Secondary Outcome
    Title Influence of Anti-hypertensive Treatment on Renal Function
    Description Improvement of the estimated glomerular filtration rate (eGFR, using the CKD-EPI equation) by more than 2.5ml/min/1.73m², compared to baseline
    Time Frame 2 years follow up

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Group A Group B Group C
    Arm/Group Description Patients treated with Aliskiren (DRI) Patients treated with ACE-I or ARB (ARB/ACE-I) Patients without any RAS inhibition (No-RAS-I)
    Measure Participants 6039 1600 1344
    Number [percentage of patients]
    32.8
    32.6
    33.9
    21. Secondary Outcome
    Title Influence of Anti-hypertensive Treatment on Renal Function
    Description Improvement of the estimated glomerular filtration rate (eGFR, using the CKD-EPI equation) by more than 2.5ml/min/1.73m², compared to baseline
    Time Frame 3 years follow up

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Group A Group B Group C
    Arm/Group Description Patients treated with Aliskiren (DRI) Patients treated with ACE-I or ARB (ARB/ACE-I) Patients without any RAS inhibition (No-RAS-I)
    Measure Participants 1678 429 262
    Number [percentage of patients]
    32.7
    28.2
    28.6

    Adverse Events

    Time Frame Baseline to 2 years follow up
    Adverse Event Reporting Description The total of affected participants refer to all patients with any SAE, regardless of event frequencies. Patients with a given SAE are only counted for SAE occurring at least 10 times in the total group.
    Arm/Group Title Group A Group B Group C
    Arm/Group Description Patients treated with Aliskiren (DRI) Patients treated with ACE-I or ARB (ARB/ACE-I) Patients without any RAS inhibition (No-RAS-I)
    All Cause Mortality
    Group A Group B Group C
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Group A Group B Group C
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 649/10177 (6.4%) 136/2696 (5%) 84/2113 (4%)
    Blood and lymphatic system disorders
    Anaemia 7/10177 (0.1%) 0/2696 (0%) 0/2113 (0%)
    Iron deficiency anaemia 3/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Anaemia of malignant disease 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Idiopathic thrombocytopenic purpura 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Lymphadenopathy 0/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Nephrogenic anaemia 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Thrombocytopenia 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Cardiac disorders
    Angina pectoris 49/10177 (0.5%) 12/2696 (0.4%) 5/2113 (0.2%)
    Cardiac failure 52/10177 (0.5%) 10/2696 (0.4%) 3/2113 (0.1%)
    Atrial fibrillation 46/10177 (0.5%) 10/2696 (0.4%) 1/2113 (0%)
    Coronary artery disease 36/10177 (0.4%) 8/2696 (0.3%) 2/2113 (0.1%)
    Myocardial infarction 27/10177 (0.3%) 3/2696 (0.1%) 7/2113 (0.3%)
    Acute myocardial infarction 14/10177 (0.1%) 6/2696 (0.2%) 1/2113 (0%)
    Left ventricular hypertrophy 17/10177 (0.2%) 3/2696 (0.1%) 0/2113 (0%)
    Arrhythmia 10/10177 (0.1%) 1/2696 (0%) 0/2113 (0%)
    Tachyarrhythmia 9/10177 (0.1%) 1/2696 (0%) 0/2113 (0%)
    Angina unstable 9/10177 (0.1%) 0/2696 (0%) 0/2113 (0%)
    Atrioventricular block complete 5/10177 (0%) 1/2696 (0%) 1/2113 (0%)
    Cardiac arrest 4/10177 (0%) 2/2696 (0.1%) 1/2113 (0%)
    Tachycardia 7/10177 (0.1%) 0/2696 (0%) 0/2113 (0%)
    Coronary artery stenosis 6/10177 (0.1%) 0/2696 (0%) 0/2113 (0%)
    Left ventricular dysfunction 6/10177 (0.1%) 0/2696 (0%) 0/2113 (0%)
    Ventricular fibrillation 3/10177 (0%) 2/2696 (0.1%) 1/2113 (0%)
    Aortic valve stenosis 3/10177 (0%) 1/2696 (0%) 1/2113 (0%)
    Bradyarrhythmia 5/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Aortic valve incompetence 4/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Atrial flutter 3/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Bradycardia 4/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Bundle branch block left 3/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Cardiovascular disorder 3/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Hypertensive heart disease 2/10177 (0%) 1/2696 (0%) 1/2113 (0%)
    Myocardial ischaemia 4/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Acute coronary syndrome 3/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Arteriosclerosis coronary artery 2/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Atrioventricular block 2/10177 (0%) 0/2696 (0%) 1/2113 (0%)
    Cardiac disorder 3/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Cardiogenic shock 3/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Congestive cardiomyopathy 2/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Mitral valve incompetence 3/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Ventricular extrasystoles 2/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Atrioventricular block second degree 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Cardiac failure chronic 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Cardiomyopathy 1/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Cardiopulmonary failure 1/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Coronary artery occlusion 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Coronary ostial stenosis 0/10177 (0%) 2/2696 (0.1%) 0/2113 (0%)
    Ischaemic cardiomyopathy 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Left ventricular failure 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Right ventricular failure 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Supraventricular extrasystoles 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Acute left ventricular failure 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Adams-Stokes syndrome 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Aortic valve sclerosis 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Bifascicular block 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Cardiac failure acute 0/10177 (0%) 0/2696 (0%) 1/2113 (0%)
    Cardiac failure congestive 0/10177 (0%) 0/2696 (0%) 1/2113 (0%)
    Cardiomyopathy alcoholic 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Chordae tendinae rupture 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Conduction disorder 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Cor pulmonale 0/10177 (0%) 0/2696 (0%) 1/2113 (0%)
    Coronary artery insufficiency 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Cyanosis 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Extrasystoles 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Heart alternation 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Intracardiac thrombus 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Myocardial rupture 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Palpitations 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Pericarditis 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Sick sinus syndrome 0/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Sinoatrial block 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Sudden cardiac death 0/10177 (0%) 0/2696 (0%) 1/2113 (0%)
    Supraventricular tachyarrhythmia 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Syncope 0/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Tricuspid valve incompetence 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Ventricular dysfunction 0/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Ventricular failure 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Ventricular hypertrophy 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Ventricular tachycardia 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Congenital, familial and genetic disorders
    Heart disease congenital 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Preternatural anus 0/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Ear and labyrinth disorders
    Vertigo 3/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Tinnitus 0/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Vertigo positional 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Endocrine disorders
    Hyperthyroidism 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Hyperparathyroidism secondary 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Eye disorders
    Amaurosis fugax 2/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Cataract 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Blindness unilateral 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Diabetic retinopathy 0/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Eyelid oedema 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Glaucoma 0/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Ocular ischaemic syndrome 0/10177 (0%) 0/2696 (0%) 1/2113 (0%)
    Ocular vascular disorder 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Gastrointestinal disorders
    Ascites 2/10177 (0%) 2/2696 (0.1%) 0/2113 (0%)
    Gastrointestinal haemorrhage 3/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Abdominal pain 3/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Diarrhoea 2/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Ileus 1/10177 (0%) 0/2696 (0%) 2/2113 (0.1%)
    Nausea 3/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Colitis ulcerative 0/10177 (0%) 0/2696 (0%) 2/2113 (0.1%)
    Inguinal hernia 1/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Vomiting 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Abdominal discomfort 0/10177 (0%) 0/2696 (0%) 1/2113 (0%)
    Abdominal hernia 0/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Abdominal pain upper 0/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Anal fistula 0/10177 (0%) 0/2696 (0%) 1/2113 (0%)
    Anal haemorrhage 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Colitis ischaemic 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Diverticulum 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Diverticulum intestinal 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Dysphagia 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Femoral hernia 0/10177 (0%) 0/2696 (0%) 1/2113 (0%)
    Gastric mucosal lesion 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Gastric ulcer 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Gastric ulcer haemorrhage 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Gastritis 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Gastritis erosive 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Gastrooesophageal reflux disease 0/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Lip swelling 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Mouth haemorrhage 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Pancreatic insufficiency 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Pancreatic pseudocyst 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Pancreatitis 0/10177 (0%) 0/2696 (0%) 1/2113 (0%)
    Pancreatitis acute 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Small intestinal perforation 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Umbilical hernia 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Upper gastrointestinal haemorrhage 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    General disorders
    Death 14/10177 (0.1%) 7/2696 (0.3%) 14/2113 (0.7%)
    Chest pain 13/10177 (0.1%) 2/2696 (0.1%) 2/2113 (0.1%)
    Sudden cardiac death 13/10177 (0.1%) 3/2696 (0.1%) 1/2113 (0%)
    Condition aggravated 12/10177 (0.1%) 0/2696 (0%) 1/2113 (0%)
    Multi-organ failure 8/10177 (0.1%) 0/2696 (0%) 0/2113 (0%)
    Chest discomfort 6/10177 (0.1%) 0/2696 (0%) 1/2113 (0%)
    Oedema peripheral 6/10177 (0.1%) 1/2696 (0%) 0/2113 (0%)
    Pyrexia 6/10177 (0.1%) 0/2696 (0%) 0/2113 (0%)
    General physical health deterioration 4/10177 (0%) 0/2696 (0%) 1/2113 (0%)
    Pain 2/10177 (0%) 1/2696 (0%) 1/2113 (0%)
    Asthenia 3/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Cardiac death 3/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Oedema 3/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Gait disturbance 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Inflammation 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Sudden death 1/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Accidental death 0/10177 (0%) 0/2696 (0%) 1/2113 (0%)
    Concomitant disease progression 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Device failure 0/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Drug ineffective 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Drug intolerance 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Drug therapeutic incompatibility 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Fatigue 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Generalised oedema 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Malaise 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    No adverse event 0/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Ulcer 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Hepatobiliary disorders
    Cholecystitis acute 1/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Acute hepatic failure 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Cholangitis 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Cholecystitis 0/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Cholelithiasis 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Cholestasis 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Hepatic cirrhosis 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Hepatic failure 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Hepatomegaly 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Hepatorenal syndrome 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Immune system disorders
    Antiphospholipid syndrome 0/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Transplant rejection 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Infections and infestations
    Pneumonia 18/10177 (0.2%) 1/2696 (0%) 2/2113 (0.1%)
    Sepsis 8/10177 (0.1%) 3/2696 (0.1%) 0/2113 (0%)
    Infection 4/10177 (0%) 0/2696 (0%) 1/2113 (0%)
    Bronchopneumonia 3/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Gastroenteritis 2/10177 (0%) 0/2696 (0%) 1/2113 (0%)
    Diverticulitis 1/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Intervertebral discitis 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Urosepsis 0/10177 (0%) 1/2696 (0%) 1/2113 (0%)
    Cellulitis 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Encephalitis herpes 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Endocarditis 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Enterocolitis bacterial 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Erysipelas 0/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Gangrene 0/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Gastroenteritis norovirus 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Gastrointestinal infection 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Hepatitis B 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Infectious peritonitis 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Infectious pleural effusion 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Lung infection 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Meningitis 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Meningitis herpes 0/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Osteomyelitis chronic 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Pneumococcal sepsis 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Pneumocystis jiroveci infection 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Pneumonia klebsiella 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Septic shock 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Staphylococcal infection 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Staphylococcal sepsis 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Urinary tract infection 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Wound infection 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Injury, poisoning and procedural complications
    Fall 8/10177 (0.1%) 2/2696 (0.1%) 0/2113 (0%)
    Accident 1/10177 (0%) 0/2696 (0%) 1/2113 (0%)
    Femoral neck fracture 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    In-stent coronary artery restenosis 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Radius fracture 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Wound 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Anastomotic ulcer haemorrhage 0/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Arterial restenosis 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Arteriovenous fistula thrombosis 0/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Cardiac valve replacement complication 0/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Compression fracture 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Excoriation 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Femur fracture 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Fibula fracture 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Fracture 0/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Head injury 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Humerus fracture 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Implant site reaction 0/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Joint dislocation 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Joint injury 0/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Meniscus lesion 0/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Post laminectomy syndrome 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Post procedural fistula 0/10177 (0%) 0/2696 (0%) 1/2113 (0%)
    Post procedural haemorrhage 0/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Seroma 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Spinal fracture 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Tendon rupture 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Investigations
    Blood pressure increased 41/10177 (0.4%) 4/2696 (0.1%) 1/2113 (0%)
    Blood creatinine increased 13/10177 (0.1%) 2/2696 (0.1%) 0/2113 (0%)
    Electrocardiogram QRS complex prolonged 13/10177 (0.1%) 0/2696 (0%) 1/2113 (0%)
    Blood pressure decreased 11/10177 (0.1%) 1/2696 (0%) 0/2113 (0%)
    Catheterisation cardiac 8/10177 (0.1%) 2/2696 (0.1%) 1/2113 (0%)
    Blood pressure systolic increased 9/10177 (0.1%) 0/2696 (0%) 0/2113 (0%)
    Glycosylated haemoglobin increased 9/10177 (0.1%) 0/2696 (0%) 0/2113 (0%)
    Blood glucose increased 7/10177 (0.1%) 1/2696 (0%) 0/2113 (0%)
    Blood pressure diastolic decreased 7/10177 (0.1%) 0/2696 (0%) 1/2113 (0%)
    Electrocardiogram QT prolonged 7/10177 (0.1%) 1/2696 (0%) 0/2113 (0%)
    Angiogram 6/10177 (0.1%) 1/2696 (0%) 0/2113 (0%)
    Arteriogram coronary 5/10177 (0%) 1/2696 (0%) 1/2113 (0%)
    Heart rate decreased 6/10177 (0.1%) 1/2696 (0%) 0/2113 (0%)
    Blood triglycerides increased 6/10177 (0.1%) 0/2696 (0%) 0/2113 (0%)
    Blood potassium increased 5/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Haemoglobin decreased 4/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Arthroscopy 2/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Liver function test abnormal 2/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Albumin urine present 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    C-reactive protein increased 1/10177 (0%) 0/2696 (0%) 1/2113 (0%)
    Creatinine urine increased 1/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Heart rate increased 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Laboratory test abnormal 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Alanine aminotransferase increased 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Arterial catheterisation 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Aspartate aminotransferase increased 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Blood alkaline phosphatase increased 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Blood bilirubin increased 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Blood cholesterol increased 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Blood glucose abnormal 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Blood potassium 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Blood pressure diastolic increased 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Blood pressure systolic decreased 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Blood sodium increased 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Cardiac enzymes increased 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Coagulation factor decreased 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Ejection fraction abnormal 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Electrocardiogram QRS complex abnormal 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Electrocardiogram abnormal 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Endoscopy upper gastrointestinal tract 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Gamma-glutamyltransferase increased 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    General physical condition abnormal 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Hepatic enzyme increased 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    LDL/HDL ratio increased 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Pathology test 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    QRS axis 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Urine albumin/creatinine ratio increased 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Weight increased 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Metabolism and nutrition disorders
    Diabetes mellitus 19/10177 (0.2%) 3/2696 (0.1%) 0/2113 (0%)
    Dehydration 6/10177 (0.1%) 1/2696 (0%) 0/2113 (0%)
    Cachexia 3/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Hyperkalaemia 3/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Hypokalaemia 3/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Hyperglycaemia 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Hyperlipidaemia 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Hyperuricaemia 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Hypoglycaemia 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Type 2 diabetes mellitus 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Electrolyte imbalance 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Fluid overload 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Fluid retention 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Gout 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Hypercalcaemia 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Hyponatraemia 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Hypoproteinaemia 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Hypovolaemia 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Metabolic syndrome 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Obesity 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Shock hypoglycaemic 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Musculoskeletal and connective tissue disorders
    Osteoarthritis 2/10177 (0%) 1/2696 (0%) 2/2113 (0.1%)
    Back pain 4/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Bone disorder 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Bursitis 1/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Chondromalacia 1/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Intervertebral disc protrusion 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Limb discomfort 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Arthralgia 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Arthropathy 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Fistula 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Gouty arthritis 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Lumbar spinal stenosis 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Muscular weakness 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Musculoskeletal discomfort 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Musculoskeletal pain 0/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Pain in jaw 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Periarthritis 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Rheumatoid arthritis 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Spinal disorder 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast cancer 6/10177 (0.1%) 2/2696 (0.1%) 0/2113 (0%)
    Colon cancer 5/10177 (0%) 2/2696 (0.1%) 1/2113 (0%)
    Bronchial carcinoma 4/10177 (0%) 0/2696 (0%) 1/2113 (0%)
    Prostate cancer 4/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Metastases to liver 3/10177 (0%) 0/2696 (0%) 1/2113 (0%)
    Metastatic neoplasm 3/10177 (0%) 0/2696 (0%) 1/2113 (0%)
    Brain neoplasm 3/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Metastases to peritoneum 3/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Neoplasm progression 2/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Renal cancer 2/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Adenocarcinoma 1/10177 (0%) 0/2696 (0%) 1/2113 (0%)
    Gastrointestinal carcinoma 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Hepatic cancer metastatic 1/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Lung neoplasm malignant 1/10177 (0%) 0/2696 (0%) 1/2113 (0%)
    Metastasis 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Neoplasm 1/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Non-Hodgkin's lymphoma 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Oesophageal carcinoma 1/10177 (0%) 0/2696 (0%) 1/2113 (0%)
    Ovarian cancer 1/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Rectal cancer 1/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Small cell lung cancer stage unspecified 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Abdominal neoplasm 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Acute myeloid leukaemia 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Adrenal neoplasm 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Basal cell carcinoma 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Benign neoplasm 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Bile duct cancer 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Bladder cancer 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Breast cancer metastatic 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Chronic lymphocytic leukaemia 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Colon adenoma 0/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Endometrial cancer 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Extranodal marginal zone B-cell lymphoma (MALT type) 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Gastric cancer 0/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Gastrointestinal stromal tumour 0/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Glioblastoma 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Hepatic neoplasm malignant 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Lipoma 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Lymphoma 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Malignant neoplasm of ampulla of Vater 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Metastases to central nervous system 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Metastases to lung 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Metastases to lymph nodes 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Metastases to oesophagus 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Metastases to prostate 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Metastatic carcinoma of the bladder 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Mycosis fungoides 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Myelodysplastic syndrome 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Neoplasm malignant 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Neoplasm prostate 0/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Oncologic complication 0/10177 (0%) 0/2696 (0%) 1/2113 (0%)
    Ovarian cancer metastatic 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Ovarian cancer recurrent 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Pancreatic carcinoma metastatic 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Paraneoplastic syndrome 0/10177 (0%) 0/2696 (0%) 1/2113 (0%)
    Plasmacytoma 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Prostate cancer recurrent 0/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Prostatic adenoma 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Refractory anaemia 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Renal cell carcinoma 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Thyroid adenoma 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Tumour haemorrhage 0/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Uterine cancer 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Nervous system disorders
    Cerebrovascular accident 41/10177 (0.4%) 5/2696 (0.2%) 11/2113 (0.5%)
    Syncope 14/10177 (0.1%) 4/2696 (0.1%) 0/2113 (0%)
    Transient ischaemic attack 16/10177 (0.2%) 2/2696 (0.1%) 0/2113 (0%)
    Dizziness 7/10177 (0.1%) 2/2696 (0.1%) 1/2113 (0%)
    Hemiparesis 7/10177 (0.1%) 1/2696 (0%) 0/2113 (0%)
    Cerebral infarction 2/10177 (0%) 3/2696 (0.1%) 1/2113 (0%)
    Aphasia 4/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Carotid artery stenosis 5/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Cerebral ischaemia 5/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Cerebral haemorrhage 3/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Coma 2/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Diabetic neuropathy 1/10177 (0%) 2/2696 (0.1%) 0/2113 (0%)
    Headache 1/10177 (0%) 1/2696 (0%) 1/2113 (0%)
    Loss of consciousness 3/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Parkinson's disease 2/10177 (0%) 0/2696 (0%) 1/2113 (0%)
    Autonomic nervous system imbalance 1/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Carotid artery occlusion 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Convulsion 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Dementia 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Hypoxic-ischaemic encephalopathy 1/10177 (0%) 0/2696 (0%) 1/2113 (0%)
    Ischaemic stroke 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Speech disorder 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Thalamic infarction 1/10177 (0%) 0/2696 (0%) 1/2113 (0%)
    Amnesia 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Apallic syndrome 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Brain injury 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Brain stem infarction 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Brain stem ischaemia 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Brain stem stroke 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Carotid artery dissection 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Cerebellar infarction 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Cerebral artery embolism 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Cerebral disorder 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Coma hepatic 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Dementia Alzheimer's type 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Demyelination 0/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Disturbance in attention 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Dysarthria 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Embolic stroke 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Epilepsy 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Facial paresis 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Haemorrhage intracranial 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Hemiplegia 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Hepatic encephalopathy 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Hypertonia 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Hypotonia 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    IIIrd nerve paresis 0/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Intercostal neuralgia 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Memory impairment 0/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Monoplegia 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Movement disorder 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Muscle spasticity 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Myelitis 0/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Nervous system disorder 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Neurological symptom 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Orthostatic intolerance 0/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Paralysis 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Paresis 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Parkinsonism 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Polyneuropathy 0/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Somnolence 0/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    VIIth nerve paralysis 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Psychiatric disorders
    Depression 6/10177 (0.1%) 4/2696 (0.1%) 0/2113 (0%)
    Mental disorder 3/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Alcohol abuse 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Anxiety 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Completed suicide 1/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Panic attack 1/10177 (0%) 0/2696 (0%) 1/2113 (0%)
    Stress 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Agoraphobia 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Confusional state 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Delirium tremens 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Disorientation 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Drug dependence 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Expressive language disorder 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Generalised anxiety disorder 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Insomnia 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Panic disorder 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Psychiatric symptom 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Psychotic disorder 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Schizophrenia 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Social phobia 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Somatoform disorder 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Withdrawal syndrome 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Renal and urinary disorders
    Renal failure 15/10177 (0.1%) 3/2696 (0.1%) 1/2113 (0%)
    Renal failure acute 6/10177 (0.1%) 2/2696 (0.1%) 1/2113 (0%)
    Renal failure chronic 7/10177 (0.1%) 0/2696 (0%) 2/2113 (0.1%)
    Nephropathy 3/10177 (0%) 2/2696 (0.1%) 0/2113 (0%)
    Diabetic nephropathy 2/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Nephrolithiasis 1/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Renal colic 1/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Urinary retention 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Albuminuria 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Calculus urethral 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Hypertensive nephropathy 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Incontinence 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Nephroangiosclerosis 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Nephrotic syndrome 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Renal artery stenosis 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Renal disorder 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Urinary tract obstruction 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Reproductive system and breast disorders
    Benign prostatic hyperplasia 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Breast calcifications 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Erectile dysfunction 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Prostatic atrophy 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Prostatitis 0/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 41/10177 (0.4%) 2/2696 (0.1%) 3/2113 (0.1%)
    Chronic obstructive pulmonary disease 10/10177 (0.1%) 1/2696 (0%) 1/2113 (0%)
    Pulmonary embolism 10/10177 (0.1%) 0/2696 (0%) 1/2113 (0%)
    Pulmonary oedema 6/10177 (0.1%) 1/2696 (0%) 0/2113 (0%)
    Respiratory failure 7/10177 (0.1%) 0/2696 (0%) 0/2113 (0%)
    Dyspnoea exertional 5/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Pleural effusion 3/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Epistaxis 3/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Hyperventilation 3/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Emphysema 1/10177 (0%) 0/2696 (0%) 1/2113 (0%)
    Lung disorder 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Pneumonia aspiration 1/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Pulmonary congestion 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Respiratory distress 0/10177 (0%) 0/2696 (0%) 2/2113 (0.1%)
    Sleep apnoea syndrome 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Acute respiratory failure 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Aspiration 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Asthma 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Bronchial disorder 0/10177 (0%) 0/2696 (0%) 1/2113 (0%)
    Bronchial secretion retention 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Chronic respiratory failure 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Cough 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Dyspnoea at rest 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Hypoxia 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Interstitial lung disease 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Obstructive airways disorder 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Pleural disorder 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Snoring 0/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Stridor 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Skin and subcutaneous tissue disorders
    Angioedema 3/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Skin ulcer 3/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Diabetic foot 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Dermatitis allergic 0/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Petechiae 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Pigmentation disorder 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Pruritus 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Rash 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Swelling face 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Social circumstances
    Joint prosthesis user 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Surgical and medical procedures
    Percutaneous coronary intervention 22/10177 (0.2%) 1/2696 (0%) 1/2113 (0%)
    Coronary angioplasty 10/10177 (0.1%) 1/2696 (0%) 1/2113 (0%)
    Stent placement 10/10177 (0.1%) 1/2696 (0%) 1/2113 (0%)
    Surgery 8/10177 (0.1%) 2/2696 (0.1%) 0/2113 (0%)
    Vascular graft 8/10177 (0.1%) 1/2696 (0%) 1/2113 (0%)
    Coronary arterial stent insertion 4/10177 (0%) 3/2696 (0.1%) 1/2113 (0%)
    Coronary artery bypass 6/10177 (0.1%) 2/2696 (0.1%) 0/2113 (0%)
    Implantable defibrillator insertion 8/10177 (0.1%) 0/2696 (0%) 0/2113 (0%)
    Rehabilitation therapy 6/10177 (0.1%) 1/2696 (0%) 0/2113 (0%)
    Angioplasty 4/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Cardiac pacemaker insertion 4/10177 (0%) 0/2696 (0%) 1/2113 (0%)
    Arterial stent insertion 3/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Cardioversion 1/10177 (0%) 3/2696 (0.1%) 0/2113 (0%)
    Hospitalisation 0/10177 (0%) 2/2696 (0.1%) 2/2113 (0.1%)
    Aortic valve replacement 1/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Cholecystectomy 1/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Colectomy 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Dialysis 1/10177 (0%) 0/2696 (0%) 1/2113 (0%)
    Haemodialysis 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Knee arthroplasty 1/10177 (0%) 0/2696 (0%) 1/2113 (0%)
    Sigmoidectomy 1/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Varicose vein operation 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Adrenalectomy 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Aortic bypass 0/10177 (0%) 0/2696 (0%) 1/2113 (0%)
    Bursa removal 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Cardiac pacemaker revision 0/10177 (0%) 0/2696 (0%) 1/2113 (0%)
    Cardiac rehabilitation therapy 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Carotid artery stent insertion 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Cataract operation 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Catheter placement 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Central venous catheterisation 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Cerebrovascular operation 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Eye operation 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Female genital operation 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Gastrostomy tube insertion 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Haematoma evacuation 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Inguinal hernia repair 0/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Knee operation 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Lymphadenectomy 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Malignant tumour excision 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Mastectomy 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Mechanical ventilation 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Mitral valve repair 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Peripheral artery angioplasty 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Phlebectomy 0/10177 (0%) 0/2696 (0%) 1/2113 (0%)
    Resuscitation 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Spinal fusion surgery 0/10177 (0%) 0/2696 (0%) 1/2113 (0%)
    Therapeutic procedure 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Tracheostomy 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Tumour excision 0/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Vascular disorders
    Hypertensive crisis 77/10177 (0.8%) 9/2696 (0.3%) 4/2113 (0.2%)
    Hypertension 41/10177 (0.4%) 4/2696 (0.1%) 4/2113 (0.2%)
    Peripheral arterial occlusive disease 11/10177 (0.1%) 1/2696 (0%) 0/2113 (0%)
    Circulatory collapse 7/10177 (0.1%) 1/2696 (0%) 0/2113 (0%)
    Blood pressure inadequately controlled 5/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Hypotension 5/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Arterial occlusive disease 3/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Deep vein thrombosis 3/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Infarction 3/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Venous insufficiency 1/10177 (0%) 1/2696 (0%) 1/2113 (0%)
    Venous thrombosis 2/10177 (0%) 0/2696 (0%) 1/2113 (0%)
    Aneurysm 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Aortic aneurysm 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Aortic aneurysm rupture 0/10177 (0%) 0/2696 (0%) 2/2113 (0.1%)
    Aortic arteriosclerosis 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Aortic dissection 0/10177 (0%) 1/2696 (0%) 1/2113 (0%)
    Aortic stenosis 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Arteriosclerosis 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Blood pressure fluctuation 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Pelvic venous thrombosis 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Thrombophlebitis 1/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Thrombosis 2/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Antiphospholipid syndrome 0/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Arterial haemorrhage 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Arterial stenosis 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Cerebrovascular accident 0/10177 (0%) 0/2696 (0%) 1/2113 (0%)
    Embolism 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Femoral artery occlusion 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Haematoma 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Haemorrhage 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Hypertensive emergency 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Intermittent claudication 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Leriche syndrome 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Lymphocele 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Macroangiopathy 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Malignant hypertension 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Peripheral vascular disorder 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Vascular compression 0/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Venous stenosis 1/10177 (0%) 0/2696 (0%) 0/2113 (0%)
    Withdrawal hypertension 0/10177 (0%) 1/2696 (0%) 0/2113 (0%)
    Other (Not Including Serious) Adverse Events
    Group A Group B Group C
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 211/10177 (2.1%) 41/2696 (1.5%) 14/2113 (0.7%)
    Cardiac disorders
    Left ventricular hypertrophy 12/10177 (0.1%) 1/2696 (0%) 2/2113 (0.1%)
    Atrial fibrillation 1/10177 (0%) 3/2696 (0.1%) 0/2113 (0%)
    Infections and infestations
    Tracheobronchitis 1/10177 (0%) 3/2696 (0.1%) 1/2113 (0%)
    Investigations
    Blood creatinine increased 26/10177 (0.3%) 4/2696 (0.1%) 1/2113 (0%)
    Blood cholesterol increased 20/10177 (0.2%) 1/2696 (0%) 3/2113 (0.1%)
    Blood glucose increased 21/10177 (0.2%) 3/2696 (0.1%) 0/2113 (0%)
    Blood triglycerides increased 17/10177 (0.2%) 0/2696 (0%) 2/2113 (0.1%)
    C-reactive protein increased 17/10177 (0.2%) 1/2696 (0%) 1/2113 (0%)
    Haemoglobin decreased 14/10177 (0.1%) 2/2696 (0.1%) 1/2113 (0%)
    Blood pressure increased 12/10177 (0.1%) 3/2696 (0.1%) 1/2113 (0%)
    Electrocardiogram QRS complex prolonged 13/10177 (0.1%) 2/2696 (0.1%) 0/2113 (0%)
    Glycosylated haemoglobin increased 12/10177 (0.1%) 3/2696 (0.1%) 0/2113 (0%)
    Metabolism and nutrition disorders
    Diabetes mellitus 0/10177 (0%) 4/2696 (0.1%) 0/2113 (0%)
    Nervous system disorders
    Dizziness 8/10177 (0.1%) 4/2696 (0.1%) 0/2113 (0%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 34/10177 (0.3%) 4/2696 (0.1%) 2/2113 (0.1%)
    Vascular disorders
    Hypertension 3/10177 (0%) 3/2696 (0.1%) 0/2113 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE 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.

    Results Point of Contact

    Name/Title Professor Dr. Uwe Zeymer
    Organization Foundation Stiftung Institut fuer Herzinfarktforschung Ludwigshafen, Germany
    Phone +49 621 503 2813
    Email Uwe.Zeymer@t-online.de
    Responsible Party:
    Stiftung Institut fuer Herzinfarktforschung
    ClinicalTrials.gov Identifier:
    NCT01454583
    Other Study ID Numbers:
    • 3A-Registry
    First Posted:
    Oct 19, 2011
    Last Update Posted:
    Jul 21, 2016
    Last Verified:
    Jun 1, 2016