The Effect of Losartan and Losartan Plus Isosorbide Mononitrate on Central Blood Pressure Measurements (0954-317)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00943852
First received: July 21, 2009
Last updated: March 31, 2014
Last verified: March 2014
Results First Received: April 27, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Pharmacodynamics Study;   Intervention Model: Crossover Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Diagnostic
Condition: Hypertension
Interventions: Drug: losartan potassium
Drug: Comparator: isosorbide mononitrate (ISMN)
Drug: Comparator: losartan + ISMN
Drug: Comparator: Placebo

  Participant Flow
  Hide Participant Flow

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

First Patient Entered: 31-Aug-2006

Last Patient Last Visit: 11-Dec-2006

Number of Sites: 1


Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Placebo / Losartan / Losartan + ISMN / Losartan + ISMN / ISMN Placebo / Losartan 100 mg / Losartan 100 mg + Isosorbide Mononitrate (ISMN) 15 mg / Losartan 100 mg + ISMN 60 mg / ISMN 60 mg – single dose with ≥ 4 days washout between doses
Losartan / ISMN / Losartan + ISMN / Placebo / Losartan + ISMN Losartan 100 mg / ISMN 60 mg / Losartan 100 mg + ISMN 60 mg / Placebo / Losartan 100 mg + ISMN 15 mg – single dose with ≥ 4 days washout between doses
ISMN / Losartan + ISMN / Placebo / Losartan / Losartan + ISMN ISMN 60 mg / Losartan 100 mg + ISMN 15 mg / Placebo / Losartan 100 mg / Losartan 100 mg + ISMN 60 mg – single dose with ≥ 4 days washout between doses
Losartan + ISMN / Losartan + ISMN / Losartan / ISMN / Placebo Losartan 100 mg + ISMN 15 mg / Losartan 100 mg + ISMN 60 mg / Losartan 100 mg / ISMN 60 mg / Placebo – single dose with ≥ 4 days washout between doses
Losartan + ISMN / Placebo / ISMN / Losartan + ISMN / Losartan Losartan 100 mg + ISMN 60 mg / Placebo / ISMN 60 mg / Losartan 100 mg + ISMN 15 mg / Losartan 100 mg – single dose with ≥ 4 days washout between doses
Placebo / ISMN / Losartan / Losartan + ISMN / Losartan + ISMN Placebo / ISMN 60 mg / Losartan 100 mg / Losartan 100 mg + ISMN 60 mg / Losartan 100 mg + ISMN 15 mg – single dose with ≥ 4 days washout between doses
Losartan / Losartan + ISMN / ISMN / Placebo / Losartan + ISMN Losartan 100 mg / Losartan 100 mg + ISMN 15 mg / ISMN 60 mg / Placebo / Losartan 100 mg + ISMN 60 mg – single dose with ≥ 4 days washout between doses
ISMN / Losartan + ISMN / Losartan + ISMN / Losartan / Placebo ISMN 60 mg / Losartan 100 mg + ISMN 60 mg / Losartan 100 mg + ISMN 15 mg / Losartan 100 mg / Placebo – single dose with ≥ 4 days washout between doses
Losartan + ISMN / Placebo / Losartan + ISMN / ISMN / Losartan Losartan 100 mg + ISMN 15 mg / Placebo / Losartan 100 mg + ISMN 60 mg / ISMN 60 mg / Losartan 100 mg – single dose with ≥ 4 days washout between doses
Losartan + ISMN / Losartan / Placebo / Losartan + ISMN / ISMN Losartan 100 mg + ISMN 60 mg / Losartan 100 mg / Placebo / Losartan 100 mg + ISMN 15 mg / ISMN 60 mg – single dose with ≥ 4 days washout between doses

Participant Flow for 9 periods

Period 1:   First Period of Treatment Intervention
    Placebo / Losartan / Losartan + ISMN / Losartan + ISMN / ISMN     Losartan / ISMN / Losartan + ISMN / Placebo / Losartan + ISMN     ISMN / Losartan + ISMN / Placebo / Losartan / Losartan + ISMN     Losartan + ISMN / Losartan + ISMN / Losartan / ISMN / Placebo     Losartan + ISMN / Placebo / ISMN / Losartan + ISMN / Losartan     Placebo / ISMN / Losartan / Losartan + ISMN / Losartan + ISMN     Losartan / Losartan + ISMN / ISMN / Placebo / Losartan + ISMN     ISMN / Losartan + ISMN / Losartan + ISMN / Losartan / Placebo     Losartan + ISMN / Placebo / Losartan + ISMN / ISMN / Losartan     Losartan + ISMN / Losartan / Placebo / Losartan + ISMN / ISMN  
STARTED     2     1     1     2     1     1     2     1     1     1  
COMPLETED     2     1     1     2     1     1     2     1     1     1  
NOT COMPLETED     0     0     0     0     0     0     0     0     0     0  

Period 2:   Washout Period After Period 1 Treatment
    Placebo / Losartan / Losartan + ISMN / Losartan + ISMN / ISMN     Losartan / ISMN / Losartan + ISMN / Placebo / Losartan + ISMN     ISMN / Losartan + ISMN / Placebo / Losartan / Losartan + ISMN     Losartan + ISMN / Losartan + ISMN / Losartan / ISMN / Placebo     Losartan + ISMN / Placebo / ISMN / Losartan + ISMN / Losartan     Placebo / ISMN / Losartan / Losartan + ISMN / Losartan + ISMN     Losartan / Losartan + ISMN / ISMN / Placebo / Losartan + ISMN     ISMN / Losartan + ISMN / Losartan + ISMN / Losartan / Placebo     Losartan + ISMN / Placebo / Losartan + ISMN / ISMN / Losartan     Losartan + ISMN / Losartan / Placebo / Losartan + ISMN / ISMN  
STARTED     2     1     1     2     1     1     2     1     1     1  
COMPLETED     2     1     1     1     1     1     2     1     1     1  
NOT COMPLETED     0     0     0     1     0     0     0     0     0     0  
BP too low for dosing at the next period                 0                 0                 0                 1                 0                 0                 0                 0                 0                 0  

Period 3:   Second Period of Treatment Intervention
    Placebo / Losartan / Losartan + ISMN / Losartan + ISMN / ISMN     Losartan / ISMN / Losartan + ISMN / Placebo / Losartan + ISMN     ISMN / Losartan + ISMN / Placebo / Losartan / Losartan + ISMN     Losartan + ISMN / Losartan + ISMN / Losartan / ISMN / Placebo     Losartan + ISMN / Placebo / ISMN / Losartan + ISMN / Losartan     Placebo / ISMN / Losartan / Losartan + ISMN / Losartan + ISMN     Losartan / Losartan + ISMN / ISMN / Placebo / Losartan + ISMN     ISMN / Losartan + ISMN / Losartan + ISMN / Losartan / Placebo     Losartan + ISMN / Placebo / Losartan + ISMN / ISMN / Losartan     Losartan + ISMN / Losartan / Placebo / Losartan + ISMN / ISMN  
STARTED     2     1     1     1     1     1     2     1     1     1  
COMPLETED     2     1     1     1     1     1     2     1     1     1  
NOT COMPLETED     0     0     0     0     0     0     0     0     0     0  

Period 4:   Washout Period After Period 2 Treatment
    Placebo / Losartan / Losartan + ISMN / Losartan + ISMN / ISMN     Losartan / ISMN / Losartan + ISMN / Placebo / Losartan + ISMN     ISMN / Losartan + ISMN / Placebo / Losartan / Losartan + ISMN     Losartan + ISMN / Losartan + ISMN / Losartan / ISMN / Placebo     Losartan + ISMN / Placebo / ISMN / Losartan + ISMN / Losartan     Placebo / ISMN / Losartan / Losartan + ISMN / Losartan + ISMN     Losartan / Losartan + ISMN / ISMN / Placebo / Losartan + ISMN     ISMN / Losartan + ISMN / Losartan + ISMN / Losartan / Placebo     Losartan + ISMN / Placebo / Losartan + ISMN / ISMN / Losartan     Losartan + ISMN / Losartan / Placebo / Losartan + ISMN / ISMN  
STARTED     2     1     1     1     1     1     2     1     1     1  
COMPLETED     2     1     1     1     1     0     2     1     1     1  
NOT COMPLETED     0     0     0     0     0     1     0     0     0     0  
Trial stopped early                 0                 0                 0                 0                 0                 1                 0                 0                 0                 0  

Period 5:   Third Period of Treatment Intervention
    Placebo / Losartan / Losartan + ISMN / Losartan + ISMN / ISMN     Losartan / ISMN / Losartan + ISMN / Placebo / Losartan + ISMN     ISMN / Losartan + ISMN / Placebo / Losartan / Losartan + ISMN     Losartan + ISMN / Losartan + ISMN / Losartan / ISMN / Placebo     Losartan + ISMN / Placebo / ISMN / Losartan + ISMN / Losartan     Placebo / ISMN / Losartan / Losartan + ISMN / Losartan + ISMN     Losartan / Losartan + ISMN / ISMN / Placebo / Losartan + ISMN     ISMN / Losartan + ISMN / Losartan + ISMN / Losartan / Placebo     Losartan + ISMN / Placebo / Losartan + ISMN / ISMN / Losartan     Losartan + ISMN / Losartan / Placebo / Losartan + ISMN / ISMN  
STARTED     2     1     1     1     1     0     2     1     1     1  
COMPLETED     2     1     1     1     1     0     2     1     1     1  
NOT COMPLETED     0     0     0     0     0     0     0     0     0     0  

Period 6:   Washout Period After Period 3 Treatment
    Placebo / Losartan / Losartan + ISMN / Losartan + ISMN / ISMN     Losartan / ISMN / Losartan + ISMN / Placebo / Losartan + ISMN     ISMN / Losartan + ISMN / Placebo / Losartan / Losartan + ISMN     Losartan + ISMN / Losartan + ISMN / Losartan / ISMN / Placebo     Losartan + ISMN / Placebo / ISMN / Losartan + ISMN / Losartan     Placebo / ISMN / Losartan / Losartan + ISMN / Losartan + ISMN     Losartan / Losartan + ISMN / ISMN / Placebo / Losartan + ISMN     ISMN / Losartan + ISMN / Losartan + ISMN / Losartan / Placebo     Losartan + ISMN / Placebo / Losartan + ISMN / ISMN / Losartan     Losartan + ISMN / Losartan / Placebo / Losartan + ISMN / ISMN  
STARTED     2     1     1     1     1     0     2     1     1     1  
COMPLETED     2     1     1     1     1     0     1     1     1     1  
NOT COMPLETED     0     0     0     0     0     0     1     0     0     0  
Did not meet criteria for next period                 0                 0                 0                 0                 0                 0                 1                 0                 0                 0  

Period 7:   Fourth Period of Treatment Intervention
    Placebo / Losartan / Losartan + ISMN / Losartan + ISMN / ISMN     Losartan / ISMN / Losartan + ISMN / Placebo / Losartan + ISMN     ISMN / Losartan + ISMN / Placebo / Losartan / Losartan + ISMN     Losartan + ISMN / Losartan + ISMN / Losartan / ISMN / Placebo     Losartan + ISMN / Placebo / ISMN / Losartan + ISMN / Losartan     Placebo / ISMN / Losartan / Losartan + ISMN / Losartan + ISMN     Losartan / Losartan + ISMN / ISMN / Placebo / Losartan + ISMN     ISMN / Losartan + ISMN / Losartan + ISMN / Losartan / Placebo     Losartan + ISMN / Placebo / Losartan + ISMN / ISMN / Losartan     Losartan + ISMN / Losartan / Placebo / Losartan + ISMN / ISMN  
STARTED     2     1     1     1     1     0     1     1     1     1  
COMPLETED     2     1     1     1     1     0     1     1     1     1  
NOT COMPLETED     0     0     0     0     0     0     0     0     0     0  

Period 8:   Washout Period After Period 4 Treatment
    Placebo / Losartan / Losartan + ISMN / Losartan + ISMN / ISMN     Losartan / ISMN / Losartan + ISMN / Placebo / Losartan + ISMN     ISMN / Losartan + ISMN / Placebo / Losartan / Losartan + ISMN     Losartan + ISMN / Losartan + ISMN / Losartan / ISMN / Placebo     Losartan + ISMN / Placebo / ISMN / Losartan + ISMN / Losartan     Placebo / ISMN / Losartan / Losartan + ISMN / Losartan + ISMN     Losartan / Losartan + ISMN / ISMN / Placebo / Losartan + ISMN     ISMN / Losartan + ISMN / Losartan + ISMN / Losartan / Placebo     Losartan + ISMN / Placebo / Losartan + ISMN / ISMN / Losartan     Losartan + ISMN / Losartan / Placebo / Losartan + ISMN / ISMN  
STARTED     2     1     1     1     1     0     1     1     1     1  
COMPLETED     1     1     0     0     1     0     0     0     1     1  
NOT COMPLETED     1     0     1     1     0     0     1     1     0     0  
Not taking medication per protocol                 0                 0                 0                 0                 0                 0                 0                 1                 0                 0  
Trial stopped early                 1                 0                 1                 1                 0                 0                 1                 0                 0                 0  

Period 9:   Fifth Period of Treatment Intervention
    Placebo / Losartan / Losartan + ISMN / Losartan + ISMN / ISMN     Losartan / ISMN / Losartan + ISMN / Placebo / Losartan + ISMN     ISMN / Losartan + ISMN / Placebo / Losartan / Losartan + ISMN     Losartan + ISMN / Losartan + ISMN / Losartan / ISMN / Placebo     Losartan + ISMN / Placebo / ISMN / Losartan + ISMN / Losartan     Placebo / ISMN / Losartan / Losartan + ISMN / Losartan + ISMN     Losartan / Losartan + ISMN / ISMN / Placebo / Losartan + ISMN     ISMN / Losartan + ISMN / Losartan + ISMN / Losartan / Placebo     Losartan + ISMN / Placebo / Losartan + ISMN / ISMN / Losartan     Losartan + ISMN / Losartan / Placebo / Losartan + ISMN / ISMN  
STARTED     1     1     0     0     1     0     0     0     1     1  
COMPLETED     1     1     0     0     1     0     0     0     1     1  
NOT COMPLETED     0     0     0     0     0     0     0     0     0     0  



  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.
No text entered.

Reporting Groups
  Description
All Participants in Study No text entered.

Baseline Measures
    All Participants in Study  
Number of Participants  
[units: participants]
  13  
Age  
[units: years]
Mean ( Full Range )
  57.2  
  ( 46 to 67 )  
Gender  
[units: participants]
 
Female     7  
Male     6  
Exclusionary Medication Washout  
[units: participants]
 
Yes     3  
No     10  
Diastolic Blood Pressure  
[units: mm Hg]
Mean ( Full Range )
  90.6  
  ( 77 to 103 )  
Heart Rate  
[units: Beats per Minute]
Mean ( Full Range )
  75.4  
  ( 48 to 99 )  
Systolic Blood Pressure  
[units: mm Hg]
Mean ( Full Range )
  141.5  
  ( 114 to 165 )  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Mean Augmentation Index Percent Change From Baseline After Single Doses of Losartan 100 mg Plus ISMN 60 mg Versus Single Dose of Losartan 100 mg   [ Time Frame: Baseline and 10 hours postdose ]

2.  Primary:   Mean Augmentation Index Percent Change From Baseline After Single Doses of Losartan 100 mg + ISMN 60 mg Versus Single Dose of Placebo   [ Time Frame: Baseline and 10 hours postdose ]


  Serious Adverse Events


  Other Adverse Events


  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 lower than expected Blood Pressure's in individual patients, an interim analysis was undertaken after 11 patients had completed 3 to 5 of the study periods; enough data was already collected to meet objectives, so the trial was stopped early.


  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:
unchecked 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.
unchecked 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.


Results Point of Contact:  
Name/Title: Executive Vice President, Clinical and Quantitative Sciences
Organization: Merck Sharp & Dohme Corp
phone: 1-800-672-6372


Publications of Results:

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00943852     History of Changes
Other Study ID Numbers: 0954-317, MK0954-317, 2009_610
Study First Received: July 21, 2009
Results First Received: April 27, 2010
Last Updated: March 31, 2014
Health Authority: United States: Food and Drug Administration