CVD/OSA: Study of Cardiovascular Disease and Obstructive Sleep Apnea

• Sponsor: University of Wisconsin, Madison (Other)
• Overall Status: Completed
• CT.gov ID: NCT01637623
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Enrollment: 87
• Locations: 4
• Arms: 3
• Duration (Months): 36
• Patients Per Site: 21.8
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if two medicines (allopurinol and losartan) can influence heart and blood vessel health compared to placebo in patients with sleep apnea who are using continuous positive airway pressure (CPAP).

Condition or Disease	Intervention/Treatment	Phase
Severe Obstructive Sleep Apnea (Apnea Hypopnea Index > 30 Events/Hour); Hypertension	Drug: Losartan; Drug: Allopurinol; Drug: Placebo	Phase 2

Detailed Description

The specific aims of this research project are: 1) Determine if treatment with losartan, an angiotensin type I receptor (AT1R) antagonist, or allopurinol, a XO inhibitor, normalize chemoreflex control of sympathetic outflow and ventilation and improve local vascular regulation and stiffness; and 2) Determine if these interventions reduce the severity of sleep disordered breathing and lower diurnal blood pressure.

Study Design

• Study Type: Interventional
• Actual Enrollment: 87 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Pharmacologic Interventions for Cardiovascular Disease in Obstructive Sleep Apnea
• Study Start Date: Jun 1, 2012
• Actual Primary Completion Date: Jun 1, 2015
• Actual Study Completion Date: Jun 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Losartan Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic and blood pressure within range.	Drug: Losartan; Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic. Remain at 50 mg daily for 4 more weeks or removed from study if symptomatic.
Active Comparator: Allopurinol Allopurinol 300 mg daily for 6 weeks	Drug: Allopurinol; Allopurinol 300 mg daily for 6 weeks
Placebo Comparator: Placebo Placebo capsule daily for 6 weeks	Drug: Placebo; Placebo capsule daily for 6 weeks

Outcome Measures

Primary Outcome Measures

1. Change in Muscle Sympathetic Nerve Activity Responses During Hypoxia [baseline and 6 weeks]

   The primary outcome variable is the change in the individual slope of the MSNA - SaO2 response curve at 6 weeks and baseline between treatment groups.

Secondary Outcome Measures

1. Change in Aortic Pulse Wave Velocity [baseline and 6 weeks]

   measurement of vascular stiffness assessed before and after study drug treatment

2. Cerebrovascular Conductance [baseline and 6 weeks]

   Assessment measures of cerebral blood flow during basal conditions and during graded hypoxia before and after study drug treatment. Cerebrovascular conductance (CVC) was calculated as velocity-time integral/mean arterial pressure.

3. Forearm Vascular Conductance [baseline and 6 weeks]

   Assessment measurements of forearm vascular conductance during basal conditions and during graded hypoxia before and after study drug treatment.

4. Change in Minute Ventilation at Normoxia [baseline and 6 weeks]

   assessed before and after study drug treatment

5. Change in Minute Ventilation During Hypoxia [baseline and 6 weeks]

   assessed before and after study drug treatment

6. Aortic Augmentation Index [baseline and 6 weeks]

   assessed before and after study drug treatment

7. Mean Change in PERCENT Vasodilation [baseline and 6 weeks]

   Flow-mediated vasodilation (FMD) (measurement of vascular endothelial function) assessed before and after study drug treatment

8. Apnea-Hypopnea Index [baseline and 6 weeks]

   Severity of sleep apnea assessed before and after study drug treatment

9. PERCENT Time Spent Below 88 PERCENT Oxygen Saturation [baseline and 6 weeks]

   assessed before and after study drug treatment

10. Change in Mean 24-Hour Blood Pressure (Mean Arterial Pressure) [baseline and 6 weeks]

    Change in mean 24 hour blood pressure (mean arterial pressure)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Males and females between ages of 21 and 65 years

• Apnea hypopnea index or respiratory disturbance index greater than or equal to 25 events per hour

• Subjects eligible for CPAP or BiPAP therapy

• Hypertension by clinical history/diagnosis (may be controlled with non- exclusionary medications) or average blood pressure > 140/90 mm Hg (using last two measurements in prior 12 months - or 1 prior blood pressure and 1 blood pressure at screening)

Exclusion Criteria:

• If subject not using CPAP, having AHI > 60 events/hour or oxygen saturation ≤ 65% during sleep

• Presence of clinical CV disease (coronary artery disease, angina, arrhythmias (subjects with sinus arrhythmias will be reviewed by PI for enrollment), stroke, TIA, cor pulmonale, etc.), heart failure, bruits, or diabetes mellitus by clinical diagnosis/history

• Presence of pulmonary disease that results in significant hypoxemia (resting SaO2 < 88%)

• Hypertriglyceridemia (triglycerides >300 mg/dL), diabetes or impaired glucose tolerance (fasting plasma glucose > 125 mg/dL)

• Patients taking angiotensin converting enzyme inhibitors, angiotensin receptor antagonists, potassium-sparing diuretics (without accompanying loop/thiazide diuretic), allopurinol, oxypurinol, febuxostat, amoxicillin, ampicillin, azathioprine or mercaptopurine.

• Patients with chronic kidney disease (Serum creatinine >1.5 mg/dL) or history of significant hyperkalemia (Serum potassium > 5.2 mEq/L) with ARB therapy

• Patients with history of angioedema

• Patients with bilateral,modified radical or radical mastectomies

• Patients who have a Serum potassium > 5.0 mEq/L at the screening visit

• Female patients who are pregnant (determined by urine pregnancy test) or breastfeeding

• Patients with active MRSA or VRE (vancomycin resistant enterococcus) infection

• History of adverse reaction to allopurinol,losartan, or zolpidem**

• Patients who cannot swallow oral capsules

• Patients who are hospitalized or who have been recently hospitalized (last 2 weeks)

• Inability to comply with or complete the protocol or other reasons at the discretion of the investigators

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Aurora Bay Care	Green Bay	Wisconsin	United States	54308
2	Gundersen Lutheran	La Crosse	Wisconsin	United States	54601
3	University of Wisconsin Madison	Madison	Wisconsin	United States	53705
4	Marshfield Clinic	Marshfield	Wisconsin	United States	54449

Sponsors and Collaborators

• University of Wisconsin, Madison
• National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: John Dopp, Pharm.D., UW Madison School of Pharmacy
• Principal Investigator: Barbara J Morgan, PhD, PT, UW Madison School of Medicine

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 25, 2017

More Information

Publications

None provided.

• Responsible Party: University of Wisconsin, Madison
• ClinicalTrials.gov Identifier: NCT01637623
• Other Study ID Numbers: 2012-0026; U01HL105365; A561000; PHARM/PHARMACY/PHARMACY
• First Posted: Jul 11, 2012
• Last Update Posted: Aug 14, 2020
• Last Verified: Aug 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by University of Wisconsin, Madison: Hypertension; High Blood Pressure; Sleep Apnea; Obstructive Sleep Apnea; OSA
• Additional relevant MeSH terms: Apnea; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Hypertension; Cardiovascular Diseases; Allopurinol; Losartan

Study Results

Participant Flow

Arm/Group Title	Losartan	Allopurinol	Placebo
Arm/Group Description	Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic and blood pressure within range. Losartan: Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic. Remain at 50 mg daily for 4 more weeks or removed from study if symptomatic.	Allopurinol 300 mg daily for 6 weeks Allopurinol: Allopurinol 300 mg daily for 6 weeks	Placebo capsule daily for 6 weeks Placebo: Placebo capsule daily for 6 weeks
Period Title: Overall Study
STARTED	29	30	28
Received Intervention	28	30	27
Did Not Receive Intervention	1	0	1
Analyzed	28	30	28
COMPLETED	28	30	25
NOT COMPLETED	1	0	3

Baseline Characteristics

Arm/Group Title	Losartan	Allopurinol	Placebo	Total
Arm/Group Description	Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic and blood pressure within range. Losartan: Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic. Remain at 50 mg daily for 4 more weeks or removed from study if symptomatic.	Allopurinol 300 mg daily for 6 weeks Allopurinol: Allopurinol 300 mg daily for 6 weeks	Placebo capsule daily for 6 weeks Placebo: Placebo capsule daily for 6 weeks	Total of all reporting groups
Overall Participants	28	30	28	86
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49 (12)	49 (8)	47 (9)	49 (10)
Sex: Female, Male (Count of Participants)
Female	15 53.6%	10 33.3%	9 32.1%	34 39.5%
Male	13 46.4%	20 66.7%	19 67.9%	52 60.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 3.6%	1 3.3%	2 7.1%	4 4.7%
Not Hispanic or Latino	27 96.4%	27 90%	24 85.7%	78 90.7%
Unknown or Not Reported	0 0%	2 6.7%	2 7.1%	4 4.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	1 3.6%	1 1.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	1 3.6%	0 0%	2 7.1%	3 3.5%
White	27 96.4%	28 93.3%	24 85.7%	79 91.9%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	2 6.7%	1 3.6%	3 3.5%
Region of Enrollment (participants) [Number]
United States	28 100%	30 100%	28 100%	86 100%

Outcome Measures

1. Primary Outcome

Title	Change in Muscle Sympathetic Nerve Activity Responses During Hypoxia
Description	The primary outcome variable is the change in the individual slope of the MSNA - SaO2 response curve at 6 weeks and baseline between treatment groups.
Time Frame	baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

Data is for fewer subjects than were randomized to treatment because a useable nerve signal was not obtained on all participants.

Arm/Group Title	Losartan	Allopurinol	Placebo
Arm/Group Description	Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic and blood pressure within range. Losartan: Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic. Remain at 50 mg daily for 4 more weeks or removed from study if symptomatic.	Allopurinol 300 mg daily for 6 weeks Allopurinol: Allopurinol 300 mg daily for 6 weeks	Placebo capsule daily for 6 weeks Placebo: Placebo capsule daily for 6 weeks
Measure Participants	18	23	25
Baseline	-0.54 (0.29)	-0.84 (0.47)	-0.71 (0.43)
Following 6 weeks of therapy	-0.69 (.50)	-0.66 (0.38)	-0.61 (0.40)

2. Secondary Outcome

Title	Change in Aortic Pulse Wave Velocity
Description	measurement of vascular stiffness assessed before and after study drug treatment
Time Frame	baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

Since this was a secondary outcome measure, not all participants were able to undergo this procedure since scheduling did not always allow with scheduling for primary outcome measure.

Arm/Group Title	Losartan	Allopurinol	Placebo
Arm/Group Description	Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic and blood pressure within range. Losartan: Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic. Remain at 50 mg daily for 4 more weeks or removed from study if symptomatic.	Allopurinol 300 mg daily for 6 weeks Allopurinol: Allopurinol 300 mg daily for 6 weeks	Placebo capsule daily for 6 weeks Placebo: Placebo capsule daily for 6 weeks
Measure Participants	19	20	18
Mean (95% Confidence Interval) [m/s]	-0.6	-0.03	0.2

3. Secondary Outcome

Title	Cerebrovascular Conductance
Description	Assessment measures of cerebral blood flow during basal conditions and during graded hypoxia before and after study drug treatment. Cerebrovascular conductance (CVC) was calculated as velocity-time integral/mean arterial pressure.
Time Frame	baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

Since this was a secondary outcome measure, not all participants were able to undergo this procedure since scheduling did not always allow with scheduling for primary outcome measure.

Arm/Group Title	Losartan	Allopurinol	Placebo
Arm/Group Description	Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic and blood pressure within range. Losartan: Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic. Remain at 50 mg daily for 4 more weeks or removed from study if symptomatic.	Allopurinol 300 mg daily for 6 weeks Allopurinol: Allopurinol 300 mg daily for 6 weeks	Placebo capsule daily for 6 weeks Placebo: Placebo capsule daily for 6 weeks
Measure Participants	20	20	22
baseline	0.32 (0.13)	0.27 (0.97)	0.33 (0.11)
After six weeks treatment	0.36 (0.14)	0.31 (0.12)	0.34 (0.12)

4. Secondary Outcome

Title	Forearm Vascular Conductance
Description	Assessment measurements of forearm vascular conductance during basal conditions and during graded hypoxia before and after study drug treatment.
Time Frame	baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

Participants were not able to conduct all procedures due to scheduling and on occasion, difficulty obtaining a signal. Prioritization of primary outcome measure was the goal.

Arm/Group Title	Losartan	Allopurinol	Placebo
Arm/Group Description	Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic and blood pressure within range. Losartan: Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic. Remain at 50 mg daily for 4 more weeks or removed from study if symptomatic.	Allopurinol 300 mg daily for 6 weeks Allopurinol: Allopurinol 300 mg daily for 6 weeks	Placebo capsule daily for 6 weeks Placebo: Placebo capsule daily for 6 weeks
Measure Participants	26	30	27
baseline	0.41 (0.21)	0.43 (0.2)	0.49 (0.31)
After 6 weeks of treatment	0.42 (0.17)	0.55 (0.31)	0.51 (0.29)

5. Secondary Outcome

Title	Change in Minute Ventilation at Normoxia
Description	assessed before and after study drug treatment
Time Frame	baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Losartan	Allopurinol	Placebo
Arm/Group Description	Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic and blood pressure within range. Losartan: Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic. Remain at 50 mg daily for 4 more weeks or removed from study if symptomatic.	Allopurinol 300 mg daily for 6 weeks Allopurinol: Allopurinol 300 mg daily for 6 weeks	Placebo capsule daily for 6 weeks Placebo: Placebo capsule daily for 6 weeks
Measure Participants	28	30	28
baseline - normoxia in L/min	8.9 (1.7)	9.3 (2.1)	9.3 (2.1)
six weeks - normoxia in L/min	8.9 (2.1)	9.8 (2.6)	8.8 (1.9)

6. Secondary Outcome

Title	Change in Minute Ventilation During Hypoxia
Description	assessed before and after study drug treatment
Time Frame	baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Losartan	Allopurinol	Placebo
Arm/Group Description	Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic and blood pressure within range. Losartan: Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic. Remain at 50 mg daily for 4 more weeks or removed from study if symptomatic.	Allopurinol 300 mg daily for 6 weeks Allopurinol: Allopurinol 300 mg daily for 6 weeks	Placebo capsule daily for 6 weeks Placebo: Placebo capsule daily for 6 weeks
Measure Participants	28	30	28
hypoxia - baseline in L/min*PERCENTSaO2	-0.41 (0.28)	-0.53 (0.41)	-0.44 (0.29)
hypoxia - after six weeks treatment in L/min*%SaO2	-0.37 (0.25)	-0.43 (0.37)	-0.48 (0.32)

7. Secondary Outcome

Title	Aortic Augmentation Index
Description	assessed before and after study drug treatment
Time Frame	baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

The number of participants differ between outcome measures due to difficulty in obtaining a viable signal for one outcome vs another and based on scheduling to prioritize the primary outcome measure.

Arm/Group Title	Losartan	Allopurinol	Placebo
Arm/Group Description	Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic and blood pressure within range. Losartan: Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic. Remain at 50 mg daily for 4 more weeks or removed from study if symptomatic.	Allopurinol 300 mg daily for 6 weeks Allopurinol: Allopurinol 300 mg daily for 6 weeks	Placebo capsule daily for 6 weeks Placebo: Placebo capsule daily for 6 weeks
Measure Participants	17	19	14
baseline	17.3	18.8	21.5
following six weeks of therapy	16.1	16.7	22.5

8. Secondary Outcome

Title	Mean Change in PERCENT Vasodilation
Description	Flow-mediated vasodilation (FMD) (measurement of vascular endothelial function) assessed before and after study drug treatment
Time Frame	baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

The number of participants differ between primary and secondary outcome variables due to occasional inability to obtain a viable signal for the variable and due to scheduling difficulties and prioritizing the primary outcome measure.

Arm/Group Title	Losartan	Allopurinol	Placebo
Arm/Group Description	Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic and blood pressure within range. Losartan: Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic. Remain at 50 mg daily for 4 more weeks or removed from study if symptomatic.	Allopurinol 300 mg daily for 6 weeks Allopurinol: Allopurinol 300 mg daily for 6 weeks	Placebo capsule daily for 6 weeks Placebo: Placebo capsule daily for 6 weeks
Measure Participants	17	19	14
Mean (95% Confidence Interval) [% change in Max relative FMD]	1.38	0.18	-1.06

9. Secondary Outcome

Title	Apnea-Hypopnea Index
Description	Severity of sleep apnea assessed before and after study drug treatment
Time Frame	baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

The number of participants differ between primary and secondary outcome variables due to occasional inability to obtain a viable signal for the variable and due to scheduling difficulties and prioritizing the primary outcome measure.

Arm/Group Title	Losartan	Allopurinol	Placebo
Arm/Group Description	Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic and blood pressure within range. Losartan: Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic. Remain at 50 mg daily for 4 more weeks or removed from study if symptomatic.	Allopurinol 300 mg daily for 6 weeks Allopurinol: Allopurinol 300 mg daily for 6 weeks	Placebo capsule daily for 6 weeks Placebo: Placebo capsule daily for 6 weeks
Measure Participants	28	28	26
baseline	46	33	35
after six weeks of treatment	44	45	26

10. Secondary Outcome

Title	PERCENT Time Spent Below 88 PERCENT Oxygen Saturation
Description	assessed before and after study drug treatment
Time Frame	baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

The number of participants differ between primary and secondary outcome variables due to occasional inability to obtain a viable signal for the variable and due to scheduling difficulties and prioritizing the primary outcome measure.

Arm/Group Title	Losartan	Allopurinol	Placebo
Arm/Group Description	Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic and blood pressure within range. Losartan: Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic. Remain at 50 mg daily for 4 more weeks or removed from study if symptomatic.	Allopurinol 300 mg daily for 6 weeks Allopurinol: Allopurinol 300 mg daily for 6 weeks	Placebo capsule daily for 6 weeks Placebo: Placebo capsule daily for 6 weeks
Measure Participants	28	28	26
baseline	10	5	5
following six weeks of therapy	12	8	3

11. Secondary Outcome

Title	Change in Mean 24-Hour Blood Pressure (Mean Arterial Pressure)
Description	Change in mean 24 hour blood pressure (mean arterial pressure)
Time Frame	baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

The number of participants differ between primary and secondary outcome variables due to occasional inability to obtain a viable signal for the variable and due to scheduling difficulties and prioritizing the primary outcome measure.

Arm/Group Title	Losartan	Allopurinol	Placebo
Arm/Group Description	Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic and blood pressure within range. Losartan: Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic. Remain at 50 mg daily for 4 more weeks or removed from study if symptomatic.	Allopurinol 300 mg daily for 6 weeks Allopurinol: Allopurinol 300 mg daily for 6 weeks	Placebo capsule daily for 6 weeks Placebo: Placebo capsule daily for 6 weeks
Measure Participants	23	25	20
Mean (95% Confidence Interval) [mm Hg]	-4.73	-2.58	1.02

Adverse Events

Time Frame	Up to 6 weeks
Adverse Event Reporting Description	Adverse Events Data reported for all participants who started the study, per participant flow.
Arm/Group Title	Losartan		Allopurinol		Placebo
Arm/Group Description	Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic and blood pressure within range. Losartan: Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic. Remain at 50 mg daily for 4 more weeks or removed from study if symptomatic.		Allopurinol 300 mg daily for 6 weeks Allopurinol: Allopurinol 300 mg daily for 6 weeks		Placebo capsule daily for 6 weeks Placebo: Placebo capsule daily for 6 weeks
All Cause Mortality
	Losartan		Allopurinol		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/29 (0%)		0/30 (0%)		0/28 (0%)
Serious Adverse Events
	Losartan		Allopurinol		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/29 (0%)		0/30 (0%)		0/28 (0%)
Other (Not Including Serious) Adverse Events
	Losartan		Allopurinol		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/29 (0%)		0/30 (0%)		0/28 (0%)

Limitations/Caveats

[Not Specified]

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.