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

• Sponsor: Vanderbilt University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00141778
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Enrollment: 455
• Location: 1
• Arms: 3
• Duration (Months): 64
• Patients Per Site Per Month: 7.1

Study Details

Study Description

Brief Summary

Atrial fibrillation (AF) is the most prevalent, sustained type of irregular heartbeat and affects over 2 million Americans. Post-operative AF, which leads to significant morbidity and a prolonged hospital stay, complicates 20% to 40% of cardiopulmonary bypass (CPB) surgical procedures. While recent studies indicate that interruption of the renin-angiotensin-aldosterone system by either angiotensin-converting enzyme (ACE) inhibition or AT1 receptor antagonism decreases the incidence of AF following a heart attack or cardioversion (electric shock to the heart), its effect on the incidence of post-operative AF has not been throughly studied. Studies in both animals and humans suggest that inflammation-induced atrial remodeling plays an important role in the cause of AF. Recent studies also provide evidence that activation of the renin-angiotensin-aldosterone system induces inflammation, myocyte injury, proarrhythmic electrical remodeling, and fibrosis through aldosterone.

Condition or Disease	Intervention/Treatment	Phase
Atrial Fibrillation	Drug: Placebo; Drug: Ramipril; Drug: Spironolactone	Phase 2/Phase 3

Detailed Description

AF is the most prevalent, sustained type of irregular heartbeat and affects over 2 million Americans. Post-operative atrial fibrillation(AF), which leads to significant morbidity and a prolonged hospital stay, complicates 20% to 40% of CPB surgical procedures. While recent studies indicate that interruption of the renin-angiotensin-aldosterone system by either angiotensin-converting enzyme(ACE) inhibition or angiotensin II subtype 1 (AT1) receptor antagonism decreases the incidence of AF following a heart attack or cardioversion (electric shock to the heart), its effect on the incidence of post-operative AF has not been throughly studied. Studies in both animals and humans suggest that inflammation-induced atrial remodeling plays an important role in the cause of AF. Recent studies also provide evidence that activation of the renin-angiotensin-aldosterone system induces inflammation, myocyte injury, proarrhythmic electrical remodeling, and fibrosis through aldosterone.

This study will evaluate the effectiveness of ACE inhibition and aldosterone receptor antagonism at decreasing inflammation and AF following cardiopulmonary bypass (CPB) surgery.

Study Design

• Study Type: Interventional
• Actual Enrollment: 455 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: RAAS, Inflammation, and Post-operative AF
• Study Start Date: Apr 1, 2005
• Actual Primary Completion Date: Jul 1, 2010
• Actual Study Completion Date: Aug 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo matched placebo pills daily beginning 4-7 days before surgery and continuing through discharge	Drug: Placebo; Matching placebo taken once a day; Other Names: Placebo tablet
Experimental: Ramipril Ramipril daily (2.5mg, increased to 5mg) beginning 4 to 7 days before surgery and continuing through discharge	Drug: Ramipril; Taken orally, once a day; Other Names: Angiotensin-converting enzyme inhibitor
Experimental: Spironolactone Spironolactone 25mg daily beginning 4 to 7 days before surgery and continuing through discharge	Drug: Spironolactone; Taken orally, once a day; Other Names: Mineralocorticoid Receptor Antagonist

Outcome Measures

Primary Outcome Measures

1. Postoperative Atrial Fibrillation [Measured from admission to the ICU until discharge from hospital]

   The primary endpoint of the study was the percentage of patients with electrocardiographically confirmed AF of at least 10 secs duration at any time following the end of surgery until hospital discharge, an average from 5.7 days in the ramipril group to 6.8 days in the placebo group. Patients were monitored continuously on telemetry throughout the postoperative period until discharge. Electrocardiograms were obtained for any rhythm changes detected on telemetry monitoring, and in addition, electrocardiograms were performed preoperatively, at admission to the intensive care unit, and daily starting on postoperative day 1. All electrocardiograms and rhythm strips were reviewed in a blinded fashion by a single cardiac electrophysiologist.

Secondary Outcome Measures

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

   Percentage of patients with a creatinine concentrations >2.5mg/dl

2. Hypotension [Measured during and after surgery, until discharge, from 5.7 to 6.8 days on average.]

   Percentage of patients with hypotension defined as a systolic blood pressure <90 mmHg and/or prolonged requirement for vasopressor use.

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

   Percentage of patients who had a serum potassium concentrations <3.5 milliequivalents (mEq)/L

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

   It is the time in minutes that it took to extubate the patient after surgery.

5. Length of Hospital Stay (Days) [Measured from the day of surgery until the time of hospital discharge]

6. Death [Measured until the time of hospital discharge]

   The percentage of patients in each study arm who died.

7. Stroke [Measured until the time of hospital discharge, from 5.7 to 6.8 days on average depending on the study arm.]

   Percentage of patients in each study group who experience a cerebrovascular event, confirmed by CT.

8. Perioperative Interleukin(IL)-6 Concentrations [Perioperative period]

   Interleukin-6 was measured at several time points (see time points in table) over the course of the study

9. Perioperative Plasminogen Activator Inhibitor-1 (PAI-1) Concentrations [Perioperative period]

   Plasminogen activator inhibitor-1 (PAI-1) was measured at several time points (see table) over the course of the study.

10. Perioperative C-reactive Protein (CRP) Concentrations [Perioperative period]

    C-reactive protein was measured at several time points (see table) over the course of the study.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Undergoing elective valvular heart surgery, coronary artery bypass grafting

2. If female, must be postmenopausal for at least 1 year, status-post surgical sterilization, or if of childbearing potential, utilizing adequate birth control and willing to undergo urine beta-hcg testing prior to drug treatment and throughout the study

Exclusion Criteria

1. History of AF other than remote paroxysmal AF

2. Ejection fraction less than 30%

3. Evidence of coagulopathy (INR greater than 1.7 without warfarin therapy)

4. Emergency surgery

5. History of ACE inhibitor-induced angioedema

6. Low blood pressure (systolic blood pressure less than 100 mmHg and evidence of hypoperfusion)

7. Hyperkalemia (potassium level greater than 5.0 milliequivalents (mEq)/L at study entry)

8. Impaired kidney function (serum creatinine level greater than 1.6 mg/dl)

9. Any underlying or acute disease requiring regular medication that could possibly cause complications or make implementation of the study or interpretation of the study results difficult

10. Inability to discontinue current ACE inhibitor, AT1 receptor antagonist, or aldosterone receptor antagonist therapy

11. History of alcohol or drug abuse

12. Treatment with any investigational drug in the month prior to study entry

13. Mental condition that makes it impossible to understand the nature, scope and possible consequences of the study

14. Inability to comply with the study procedures (e.g., uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study)

15. Pregnant or breastfeeding

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Vanderbilt University	Nashville	Tennessee	United States	37232

Sponsors and Collaborators

• Vanderbilt University
• National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Nancy J. Brown, M.D., Vanderbilt University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Nancy J. Brown, Professor of Medicine and Pharmacology, Vanderbilt University
• ClinicalTrials.gov Identifier: NCT00141778
• Other Study ID Numbers: 040385; R01HL077389; NCT00134862
• First Posted: Sep 1, 2005
• Last Update Posted: Mar 22, 2013
• Last Verified: Feb 1, 2013

• Keywords provided by Nancy J. Brown, Professor of Medicine and Pharmacology, Vanderbilt University: atrial fibrillation; cardiac surgery
• Additional relevant MeSH terms: Atrial Fibrillation; Inflammation; Ramipril; Spironolactone; Mineralocorticoid Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Enzyme Inhibitors; Mineralocorticoids

Study Results

Participant Flow

Recruitment Details	Patients were recruited between 2005 and 2010 from Vanderbilt University Medical Center and Brigham and Women's Hospital
Pre-assignment Detail	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

Arm/Group Title	Placebo	Ramipril	Spironolactone
Arm/Group Description	Placebo Group	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.	Mineralocorticoid Receptor (MR) Antagonist Group.Spironolactone was given as 25 mg/day.
Period Title: Randomization Prior to Study Med
STARTED	152	153	153
COMPLETED	147	151	147
NOT COMPLETED	5	2	6
Period Title: Randomization Prior to Study Med
STARTED	147	151	147
COMPLETED	145	144	143
NOT COMPLETED	2	7	4

Baseline Characteristics

Arm/Group Title	Placebo	Ramipril	Spironolactone	Total
Arm/Group Description	Placebo Group	Angiotensin-converting enzyme inhibitor group	Mineralocorticoid Receptor (MR) Antagonist group	Total of all reporting groups
Overall Participants	147	151	147	445
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	94 63.9%	101 66.9%	99 67.3%	294 66.1%
>=65 years	53 36.1%	50 33.1%	48 32.7%	151 33.9%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.0 (12.0)	58.7 (12.3)	59.2 (12.3)	59.3 (12.2)
Sex: Female, Male (Count of Participants)
Female	53 36.1%	45 29.8%	51 34.7%	149 33.5%
Male	94 63.9%	106 70.2%	96 65.3%	296 66.5%
Region of Enrollment (participants) [Number]
United States	147 100%	151 100%	147 100%	445 100%

Outcome Measures

1. Primary Outcome

Title	Postoperative Atrial Fibrillation
Description	The primary endpoint of the study was the percentage of patients with electrocardiographically confirmed AF of at least 10 secs duration at any time following the end of surgery until hospital discharge, an average from 5.7 days in the ramipril group to 6.8 days in the placebo group. Patients were monitored continuously on telemetry throughout the postoperative period until discharge. Electrocardiograms were obtained for any rhythm changes detected on telemetry monitoring, and in addition, electrocardiograms were performed preoperatively, at admission to the intensive care unit, and daily starting on postoperative day 1. All electrocardiograms and rhythm strips were reviewed in a blinded fashion by a single cardiac electrophysiologist.
Time Frame	Measured from admission to the ICU until discharge from hospital

Outcome Measure Data

Analysis Population Description

Four hundred fifty-eight patients were randomized. Of these 445 took study medication and were included in the intention-to-treat analysis.

Arm/Group Title	Placebo	Ramipril	Spironolactone
Arm/Group Description	Placebo Group	Angiotensin-converting enzyme inhibitor group	Mineralocorticoid Receptor (MR) Antagonist group
Measure Participants	147	151	147
Number [percentage of patients]	27.2	27.8	25.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ramipril, Spironolactone
	Comments	Discrete variables were compared among treatment groups with a chi-square test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.95
	Comments
	Method	Chi-squared
	Comments

2. Secondary Outcome

Title	Acute Renal Failure
Description	Percentage of patients with a creatinine concentrations >2.5mg/dl
Time Frame	Measured until the time of hospital discharge, from 5.7 to 6.8 days on average, depending on the study group.

Outcome Measure Data

Analysis Population Description

The intention-to-treat analysis included anyone who had received any study medication.

Arm/Group Title	Placebo	Ramipril	Spironolactone
Arm/Group Description	Placebo Group	Angiotensin-converting enzyme inhibitor group	Mineralocorticoid Receptor (MR) Antagonist group
Measure Participants	147	151	147
Number [percentage of patients]	5.4	0.7	0.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ramipril, Spironolactone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.006
	Comments
	Method	Chi-squared
	Comments

3. Secondary Outcome

Title	Hypotension
Description	Percentage of patients with hypotension defined as a systolic blood pressure <90 mmHg and/or prolonged requirement for vasopressor use.
Time Frame	Measured during and after surgery, until discharge, from 5.7 to 6.8 days on average.

Outcome Measure Data

Analysis Population Description

The intention-to-treat analysis included anyone who had received any medication.

Arm/Group Title	Placebo	Ramipril	Spironolactone
Arm/Group Description	Placebo Group	Angiotensin-converting enzyme inhibitor group	Mineralocorticoid Receptor (MR) Antagonist group
Measure Participants	147	151	147
Number [percentage of patients]	5.4	10.6	10.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ramipril, Spironolactone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.15
	Comments
	Method	Chi-squared
	Comments

4. Secondary Outcome

Title	Hypokalemia
Description	Percentage of patients who had a serum potassium concentrations <3.5 milliequivalents (mEq)/L
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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Ramipril	Spironolactone
Arm/Group Description	Placebo Group	Angiotensin-converting enzyme inhibitor group	Mineralocorticoid Receptor (MR) Antagonist group
Measure Participants	147	151	147
Number [percentage of patients]	11.6	13.8	6.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ramipril, Spironolactone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.14
	Comments
	Method	Chi-squared
	Comments

5. Secondary Outcome

Title	Time to Tracheal Extubation
Description	It is the time in minutes that it took to extubate the patient after surgery.
Time Frame	It is the time (in minutes) from admission to the ICU until tracheal extubation

Outcome Measure Data

Analysis Population Description

The intention-to-treat analysis included all patients who received any study medication.

Arm/Group Title	Placebo	Ramipril	Spironolactone
Arm/Group Description	Placebo Group	Angiotensin-converting enzyme inhibitor group	Mineralocorticoid Receptor (MR) Antagonist group
Measure Participants	147	151	147
Mean (Standard Deviation) [minutes]	1091.3 (3067.3)	970.1 (3548.1)	576.4 (761.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ramipril, Spironolactone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.56
	Comments
	Method	Kruskal-Wallis
	Comments

6. Secondary Outcome

Title	Length of Hospital Stay (Days)
Time Frame	Measured from the day of surgery until the time of hospital discharge

Outcome Measure Data

Analysis Population Description

The intention-to-treat analysis included anyone who had received any study medication.

Arm/Group Title	Placebo	Ramipril	Spironolactone
Arm/Group Description	Placebo Group	Angiotensin-converting enzyme inhibitor group	Mineralocorticoid Receptor (MR) Antagonist group
Measure Participants	147	151	147
Mean (Standard Deviation) [days]	6.8 (8.2)	5.7 (3.2)	5.8 (3.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ramipril, Spironolactone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.15
	Comments
	Method	Kruskal-Wallis
	Comments

7. Secondary Outcome

Title	Death
Description	The percentage of patients in each study arm who died.
Time Frame	Measured until the time of hospital discharge

Outcome Measure Data

Analysis Population Description

The intention-to-treat analysis included all patients who received any study medication.

Arm/Group Title	Placebo	Ramipril	Spironolactone
Arm/Group Description	Placebo Group	Angiotensin-converting enzyme inhibitor group	Mineralocorticoid Receptor (MR) Antagonist group
Measure Participants	147	151	147
Number [percentage of patients]	1.4	2.0	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ramipril, Spironolactone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.38
	Comments
	Method	Chi-squared
	Comments

8. Secondary Outcome

Title	Stroke
Description	Percentage of patients in each study group who experience a cerebrovascular event, confirmed by CT.
Time Frame	Measured until the time of hospital discharge, from 5.7 to 6.8 days on average depending on the study arm.

Outcome Measure Data

Analysis Population Description

The intention-to-treat analysis included all those who received any study drug.

Arm/Group Title	Placebo	Ramipril	Spironolactone
Arm/Group Description	Placebo Group	Angiotensin-converting enzyme inhibitor group	Mineralocorticoid Receptor (MR) Antagonist group
Measure Participants	147	151	147
Number [percentage of patients]	2.7	1.3	2.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ramipril, Spironolactone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.65
	Comments
	Method	Chi-squared
	Comments

9. Secondary Outcome

Title	Perioperative Interleukin(IL)-6 Concentrations
Description	Interleukin-6 was measured at several time points (see time points in table) over the course of the study
Time Frame	Perioperative period

Outcome Measure Data

Analysis Population Description

All participants included in the intention-to-treat analysis who had available plasma samples.

Arm/Group Title	Placebo	Ramipril	Spironolactone
Arm/Group Description	Placebo Group	Angiotensin-converting enzyme inhibitor group	Mineralocorticoid Receptor (MR) Antagonist group
Measure Participants	136	136	140
Initiation of surgery	4.7 (6.7)	4.6 (7.1)	6.6 (10.2)
30min intraop	12.0 (18.4)	20.5 (72.6)	11.3 (20.2)
60min intraop	15.6 (20.1)	28.8 (100.9)	17.4 (29.4)
Postop	130.0 (213.7)	202.1 (668.7)	145.7 (427.1)
Postoperative day 1	119.0 (143.1)	171.0 (208.6)	164.9 (200.2)
Postoperative day 2	100.3 (106.8)	95.5 (90.8)	109.6 (116.9)

10. Secondary Outcome

Title	Perioperative Plasminogen Activator Inhibitor-1 (PAI-1) Concentrations
Description	Plasminogen activator inhibitor-1 (PAI-1) was measured at several time points (see table) over the course of the study.
Time Frame	Perioperative period

Outcome Measure Data

Analysis Population Description

PAI-1 was measured in all subjects in the intention-to-treat analysis for which plasma was available.

Arm/Group Title	Placebo	Ramipril	Spironolactone
Arm/Group Description	Placebo Group	Angiotensin-converting enzyme inhibitor group	Mineralocorticoid Receptor (MR) Antagonist group
Measure Participants	135	133	136
Initiation of surgery	19.6 (16.6)	16.2 (11.9)	17.3 (12.0)
30min intraop	19.2 (10.7)	19.7 (12.5)	17.3 (10.9)
60min intraop	21.0 (10.9)	22.0 (13.7)	20.1 (11.7)
Postop	36.4 (24.6)	38.9 (28.0)	34.0 (22.3)
Postoperative day 1	55.2 (43.8)	47.9 (31.4)	48.9 (35.0)
Postoperative day 2	28.1 (20.4)	25.7 (17.9)	31.0 (30.5)

11. Secondary Outcome

Title	Perioperative C-reactive Protein (CRP) Concentrations
Description	C-reactive protein was measured at several time points (see table) over the course of the study.
Time Frame	Perioperative period

Outcome Measure Data

Analysis Population Description

CRP was measured in all subjects from the intention-to-treat analysis for which plasma was available at those time points.

Arm/Group Title	Placebo	Ramipril	Spironolactone
Arm/Group Description	Placebo Group	Angiotensin-converting enzyme inhibitor group	Mineralocorticoid Receptor (MR) Antagonist group
Measure Participants	127	129	126
Initiation of surgery	4.1 (6.8)	4.3 (10.8)	3.9 (7.3)
Postoperative day 1	51.4 (40.0)	49.9 (38.5)	64.3 (115)
Postoperative day 2	134.8 (137.4)	131.0 (281.5)	127.8 (84.8)
Postoperative day 3	128.3 (88.7)	164.8 (416.5)	189.4 (476.0)
Postoperative day 4	94.1 (67.3)	105.2 (96.6)	126.5 (95.4)

Adverse Events

Time Frame	Duration of hospital stay, which averaged from 5.7 to 6.8 days depending on the study arm.
Adverse Event Reporting Description	The intention-to-treat analysis included all subjects who received any study drug.
Arm/Group Title	Placebo		Ramipril		Spironolactone
Arm/Group Description	Placebo Group		Angiotensin-converting enzyme inhibitor group		Mineralocorticoid Receptor (MR) Antagonist group
All Cause Mortality
	Placebo		Ramipril		Spironolactone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Ramipril		Spironolactone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/147 (5.4%)		6/151 (4%)		5/147 (3.4%)
General disorders
Death	2/147 (1.4%)	2	3/151 (2%)	3	0/147 (0%)	0
Nervous system disorders
Stroke	4/147 (2.7%)	4	2/151 (1.3%)	2	3/147 (2%)	4
Renal and urinary disorders
Acute renal failure	8/147 (5.4%)	8	1/151 (0.7%)	1	1/147 (0.7%)	1
Respiratory, thoracic and mediastinal disorders
Pneumonia	6/147 (4.1%)	6	4/151 (2.6%)	4	2/147 (1.4%)	2
Other (Not Including Serious) Adverse Events
	Placebo		Ramipril		Spironolactone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/147 (11.6%)		21/151 (13.9%)		15/147 (10.2%)
Cardiac disorders
Hypotension	8/147 (5.4%)	8	16/151 (10.6%)	16	15/147 (10.2%)	15
General disorders
Hypokalemia	17/147 (11.6%)	17	21/151 (13.9%)	21	10/147 (6.8%)	10
Hyperkalemia	1/147 (0.7%)	1	1/151 (0.7%)	1	1/147 (0.7%)	1

Limitations/Caveats

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

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.