Renin-angiotensin-aldosterone System (RAAS), Inflammation, and Post-Operative Atrial Fibrillation (AF)

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Nancy J. Brown, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT00141778
First received: August 30, 2005
Last updated: February 19, 2013
Last verified: February 2013
Results First Received: August 3, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Condition: Atrial Fibrillation
Interventions: Drug: Placebo
Drug: Ramipril
Drug: Spironolactone

  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
Patients were recruited between 2005 and 2010 from Vanderbilt University Medical Center and Brigham and Women's Hospital

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
One week to four days prior to surgery, patients were randomized to treatment with placebo, ramipril or spironolactone. Preexisting ACE inhibitor, angiotensin receptor blocker, or MR antagonist use was stopped at randomization. Four hundred and fifty-eight patients met inclusion and were randomized

Reporting Groups
  Description
Placebo Placebo Group
Ramipril Angiotensin-Converting Enzyme Inhibitor Group. Ramipril was given as 2.5 mg the first 3 days followed by 5 mg/day, with the dose reduced to 2.5 mg/day on the first postoperative day only.
Spironolactone Mineralocorticoid Receptor (MR) Antagonist Group.Spironolactone was given as 25 mg/day.

Participant Flow for 2 periods

Period 1:   Randomization Prior to Study Med
    Placebo     Ramipril     Spironolactone  
STARTED     152     153     153  
COMPLETED     147     151     147  
NOT COMPLETED     5     2     6  
Withdrawal by Subject                 5                 2                 6  

Period 2:   Started Study Medication
    Placebo     Ramipril     Spironolactone  
STARTED     147     151     147  
COMPLETED     145     144     143  
NOT COMPLETED     2     7     4  
Met safety criteria for discontinuation                 2                 4                 3  
Withdrawal by Subject                 0                 2                 0  
Difficulty Swallowing                 0                 1                 0  
Chest Discomfort                 0                 0                 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.
No text entered.

Reporting Groups
  Description
Placebo Placebo Group
Ramipril Angiotensin-converting enzyme inhibitor group
Spironolactone Mineralocorticoid Receptor (MR) Antagonist group
Total Total of all reporting groups

Baseline Measures
    Placebo     Ramipril     Spironolactone     Total  
Number of Participants  
[units: participants]
  147     151     147     445  
Age  
[units: participants]
       
<=18 years     0     0     0     0  
Between 18 and 65 years     94     101     99     294  
>=65 years     53     50     48     151  
Age  
[units: years]
Mean ± Standard Deviation
  60.0  ± 12.0     58.7  ± 12.3     59.2  ± 12.3     59.3  ± 12.2  
Gender  
[units: participants]
       
Female     53     45     51     149  
Male     94     106     96     296  
Region of Enrollment  
[units: participants]
       
United States     147     151     147     445  



  Outcome Measures
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1.  Primary:   Postoperative Atrial Fibrillation   [ Time Frame: Measured from admission to the ICU until discharge from hospital ]

2.  Secondary:   Acute Renal Failure   [ Time Frame: Measured until the time of hospital discharge, from 5.7 to 6.8 days on average, depending on the study group. ]

3.  Secondary:   Hypotension   [ Time Frame: Measured during and after surgery, until discharge, from 5.7 to 6.8 days on average. ]

4.  Secondary:   Hypokalemia   [ Time Frame: Measured until the time of hospital discharge, which was an average of 5.7 to 6.8 days depending on the treatment arm. ]

5.  Secondary:   Time to Tracheal Extubation   [ Time Frame: It is the time (in minutes) from admission to the ICU until tracheal extubation ]

6.  Secondary:   Length of Hospital Stay (Days)   [ Time Frame: Measured from the day of surgery until the time of hospital discharge ]

7.  Secondary:   Death   [ Time Frame: Measured until the time of hospital discharge ]

8.  Secondary:   Stroke   [ Time Frame: Measured until the time of hospital discharge, from 5.7 to 6.8 days on average depending on the study arm. ]

9.  Secondary:   Perioperative Interleukin(IL)-6 Concentrations   [ Time Frame: Perioperative period ]

10.  Secondary:   Perioperative Plasminogen Activator Inhibitor-1 (PAI-1) Concentrations   [ Time Frame: Perioperative period ]

11.  Secondary:   Perioperative C-reactive Protein (CRP) Concentrations   [ Time Frame: Perioperative period ]


  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
We excluded patients with an ejection fraction less than 30% or a creatinine above 1.6 and therefore the results are not applicable to patients with left ventricular dysfunction or more severe chronic kidney disease.


  More Information
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Certain Agreements:  
Principal Investigators are NOT 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: Dr. Mias Pretorius
Organization: Vanderbilt University School of Medicine
phone: 16153430665
e-mail: mias.pretorius@vanderbilt.edu


Publications of Results:
Publications automatically indexed to this study:

Responsible Party: Nancy J. Brown, Vanderbilt University
ClinicalTrials.gov Identifier: NCT00141778     History of Changes
Obsolete Identifiers: NCT00134862
Other Study ID Numbers: 040385, R01HL077389
Study First Received: August 30, 2005
Results First Received: August 3, 2012
Last Updated: February 19, 2013
Health Authority: United States: Institutional Review Board