Trial Outcomes & Findings for Uric Acid and Hypertension in African Americans (NCT NCT00241839)

NCT ID: NCT00241839

Last Updated: 2013-07-26

Results Overview

The Diastolic BP was taken at Baseline and after 8-10 weeks of treatment or placebo while on chlorthalidone and potassium chloride. The blood pressure was measured according to "Shared Care" protocol: 15 minutes of quiet, undisturbed rest with three BP measurements obtained subsequently at 5 minute intervals. The mean of the second and third reading was the value used for analysis for both the Baseline measurement and the measurement after 8 - 10 weeks of treatment. The dependent variable is baseline value minus ending value. Measures are in millimeters of mercury (mm hg)

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 150 participants
• Primary outcome timeframe: Measured at 8-10 weeks on allopurinol / placebo
• Results posted on: 2013-07-26

Participant Flow

Recruitment was through flyers and voluntary blood pressure checks and hypertension lectures throughout the county in churches, health fairs, community art festivals, new business openings and celebrations, and in hospital lobbies, business employee lounges, store front spaces at grocery stores and super stores. Individuals also self-refered.

150 subjects signed consents;8 were withdrawn prior to randomization. All participants were placed on chlorthalidone 25mg daily for blood pressure stabilization along with potassium chloride (KCL) 40meq daily. Potassium chloride was increased to 50meq daily for those subjects whose serum potassium was less than 3.5 before baseline visit.

Participant milestones

Measure	A (Allopurinol) Chlorthalidone 25 mg and Potassium Chloride 40-50meq were given daily for 5 weeks before baseline visit for testing. After baseline testing was completed, Allopurinol 300mg daily was added for 8-10 weeks. Serum uric acid (UA) levels were checked at study visit 2 weeks post baseline. If UA levels were above 5.0 an additional 300mg allopurinol was added with total dose of 600mg daily. The dosage of allopurinol then remained constant throughout the remainder of the study. Testing was repeated at 8-10 weeks after baseline.	B(Placebo) Chlorthalidone 25 mg and Potassium Chloride 40-50meq were given daily for 5 weeks before baseline visit for testing. After baseline testing was completed, a Placebo, having the same appearance and dosage label(300mg)as allopurinol, was added for 8-10 weeks. Serum uric acid (UA) levels were checked at study visit 2 weeks post baseline. If UA levels were above 5.0 an additional placebo (300mg)was added with total dose of 600mg daily. The dosage of placebo then remained constant throughout the remainder of the study. Testing was repeated at 8-10 weeks after baseline.
Overall Study STARTED	71	71
Overall Study COMPLETED	52	53
Overall Study NOT COMPLETED	19	18

Reasons for withdrawal

Measure	A (Allopurinol) Chlorthalidone 25 mg and Potassium Chloride 40-50meq were given daily for 5 weeks before baseline visit for testing. After baseline testing was completed, Allopurinol 300mg daily was added for 8-10 weeks. Serum uric acid (UA) levels were checked at study visit 2 weeks post baseline. If UA levels were above 5.0 an additional 300mg allopurinol was added with total dose of 600mg daily. The dosage of allopurinol then remained constant throughout the remainder of the study. Testing was repeated at 8-10 weeks after baseline.	B(Placebo) Chlorthalidone 25 mg and Potassium Chloride 40-50meq were given daily for 5 weeks before baseline visit for testing. After baseline testing was completed, a Placebo, having the same appearance and dosage label(300mg)as allopurinol, was added for 8-10 weeks. Serum uric acid (UA) levels were checked at study visit 2 weeks post baseline. If UA levels were above 5.0 an additional placebo (300mg)was added with total dose of 600mg daily. The dosage of placebo then remained constant throughout the remainder of the study. Testing was repeated at 8-10 weeks after baseline.
Overall Study Withdrawal by Subject	18	17
Overall Study Adverse Event	1	1

Baseline Characteristics

Uric Acid and Hypertension in African Americans

Baseline characteristics by cohort

Measure	A (Allopurinol) n=71 Participants Chlorthalidone 25 mg and Potassium Chloride 40-50meq were given daily for 5 weeks before baseline visit for testing. After baseline testing was completed, Allopurinol 300mg daily was added for 8-10 weeks. Serum uric acid (UA) levels were checked at study visit 2 weeks post baseline. If UA levels were above 5.0 an additional 300mg allopurinol was added with total dose of 600mg daily. The dosage of allopurinol then remained constant throughout the remainder of the study. Testing was repeated at 8-10 weeks after baseline.	B (Placebo) n=71 Participants Chlorthalidone 25 mg and Potassium Chloride 40-50meq were given daily for 5 weeks before baseline visit for testing. After baseline testing was completed, a Placebo, having the same appearance and dosage label(300mg)as allopurinol, was added for 8-10 weeks. Serum uric acid (UA) levels were checked at study visit 2 weeks post baseline. If UA levels were above 5.0 an additional placebo (300mg)was added with total dose of 600mg daily. The dosage of placebo then remained constant throughout the remainder of the study. Testing was repeated at 8-10 weeks after baseline.	Total n=142 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	70 Participants n=5 Participants	71 Participants n=7 Participants	141 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Age Continuous	47.7 years STANDARD_DEVIATION 10.1 • n=5 Participants	48.0 years STANDARD_DEVIATION 7.7 • n=7 Participants	47.9 years STANDARD_DEVIATION 8.8 • n=5 Participants
Sex: Female, Male Female	51 Participants n=5 Participants	51 Participants n=7 Participants	102 Participants n=5 Participants
Sex: Female, Male Male	20 Participants n=5 Participants	20 Participants n=7 Participants	40 Participants n=5 Participants
Region of Enrollment United States	71 participants n=5 Participants	71 participants n=7 Participants	142 participants n=5 Participants

PRIMARY outcome

Timeframe: Measured at 8-10 weeks on allopurinol / placebo

Population: Participants were individuals with essential hypertension (BP 140/90-160/100) on none or up 2 antihypertensive drugs without any other chronic condition or illness. For their data to be included in analysis they had to complete the study (includes baseline to last visit).

The Diastolic BP was taken at Baseline and after 8-10 weeks of treatment or placebo while on chlorthalidone and potassium chloride. The blood pressure was measured according to "Shared Care" protocol: 15 minutes of quiet, undisturbed rest with three BP measurements obtained subsequently at 5 minute intervals.

The mean of the second and third reading was the value used for analysis for both the Baseline measurement and the measurement after 8 - 10 weeks of treatment. The dependent variable is baseline value minus ending value.

Measures are in millimeters of mercury (mm hg)

Outcome measures

Measure	A (Allopurinol) n=52 Participants Chlorthalidone 25 mg and Potassium Chloride 40-50meq were given daily for 5 weeks before baseline visit for testing. After baseline testing was completed, Allopurinol 300mg daily was added for 8-10 weeks. Serum uric acid (UA) levels were checked at study visit 2 weeks post baseline. If UA levels were above 5.0 an additional 300mg allopurinol was added with total dose of 600mg daily. The dosage of allopurinol then remained constant throughout the remainder of the study. Testing was repeated at 8-10 weeks after baseline.	B (Placebo) n=53 Participants Chlorthalidone 25 mg and Potassium Chloride 40-50meq were given daily for 5 weeks before baseline visit for testing. After baseline testing was completed, Placebo 300mg daily (identical in size, color, and dosage as allopurinol) was added for 8-10 weeks. Serum uric acid (UA) levels were checked at study visit 2 weeks post baseline. If UA levels were above 5.0 an additional 300mg placebo was added with total dose of 600mg daily. The dosage of placebo then remained constant throughout the remainder of the study. Testing was repeated at 8-10 weeks after baseline.
Change in Diastolic Blood Pressure by Cuff 8-10 Weeks Minus Baseline	3.44 mm Hg Standard Deviation 12.25	-0.83 mm Hg Standard Deviation 10.63

PRIMARY outcome

Timeframe: Measured at 8-10 weeks on allopurinol or placebo

Population: Participants were individuals with essential hypertension (BP 140/90-160/100) on none or up 2 antihypertensive drugs without any other chronic condition or illness. For their data to be included in analysis they had to complete the study (includes baseline to last visit).

The systolic BP was taken at Baseline and after 8-10 weeks of treatment on placebo, while on chlorthalidone and potassium chloride. The blood pressure was measured according to "Shared Care" protocol: 15 minutes of quiet, undisturbed rest with three BP measurements obtained subsequently at 5 minute intervals.

The mean of the second and third reading was the value used for analysis for both the Baseline measurement and the measurement after 8 - 10 weeks of treatment. The dependent variable is baseline value minus ending value.

Measures are in millimeters of mercury (mm hg)

Outcome measures

Measure	A (Allopurinol) n=52 Participants Chlorthalidone 25 mg and Potassium Chloride 40-50meq were given daily for 5 weeks before baseline visit for testing. After baseline testing was completed, Allopurinol 300mg daily was added for 8-10 weeks. Serum uric acid (UA) levels were checked at study visit 2 weeks post baseline. If UA levels were above 5.0 an additional 300mg allopurinol was added with total dose of 600mg daily. The dosage of allopurinol then remained constant throughout the remainder of the study. Testing was repeated at 8-10 weeks after baseline.	B (Placebo) n=53 Participants Chlorthalidone 25 mg and Potassium Chloride 40-50meq were given daily for 5 weeks before baseline visit for testing. After baseline testing was completed, Placebo 300mg daily (identical in size, color, and dosage as allopurinol) was added for 8-10 weeks. Serum uric acid (UA) levels were checked at study visit 2 weeks post baseline. If UA levels were above 5.0 an additional 300mg placebo was added with total dose of 600mg daily. The dosage of placebo then remained constant throughout the remainder of the study. Testing was repeated at 8-10 weeks after baseline.
Change in Systolic Blood Pressure by Cuff After 8-10 Weeks Minus Baseline	0.21 mm Hg Standard Deviation 7.37	-0.95 mm Hg Standard Deviation 8.90

SECONDARY outcome

Timeframe: Baseline and end of treatment (8-10 weeks on allopurinol / placebo)

Population: We obtained over 90% of those with cuff measures on the 24 hour BP measures (ABPM).

Subjects had 24 hr blood pressure monitoring (ABPM) at baseline and treatment end. The readings were averaged and the changes from baseline to treatment end were compared.

Outcome measures

Measure	A (Allopurinol) n=49 Participants Chlorthalidone 25 mg and Potassium Chloride 40-50meq were given daily for 5 weeks before baseline visit for testing. After baseline testing was completed, Allopurinol 300mg daily was added for 8-10 weeks. Serum uric acid (UA) levels were checked at study visit 2 weeks post baseline. If UA levels were above 5.0 an additional 300mg allopurinol was added with total dose of 600mg daily. The dosage of allopurinol then remained constant throughout the remainder of the study. Testing was repeated at 8-10 weeks after baseline.	B (Placebo) n=50 Participants Chlorthalidone 25 mg and Potassium Chloride 40-50meq were given daily for 5 weeks before baseline visit for testing. After baseline testing was completed, Placebo 300mg daily (identical in size, color, and dosage as allopurinol) was added for 8-10 weeks. Serum uric acid (UA) levels were checked at study visit 2 weeks post baseline. If UA levels were above 5.0 an additional 300mg placebo was added with total dose of 600mg daily. The dosage of placebo then remained constant throughout the remainder of the study. Testing was repeated at 8-10 weeks after baseline.
Change in Overall Mean BP From Those Obtained by 24 Hour Ambulatory Blood Pressure Measurements (ABPM) 8-10 Weeks Minus Baseline.	-5.9 mm Hg Standard Deviation 11.9	0.90 mm Hg Standard Deviation 8.91

SECONDARY outcome

Timeframe: Baseline UA levels compared to end of treatment levels (8-10 weeks on allopurinol / placebo)

Population: Change in uric acid from baseline to end of treatment.

Subjects on allopurinol are expected to lower their uric acid levels relative to placebo.

Outcome measures

Measure	A (Allopurinol) n=50 Participants Chlorthalidone 25 mg and Potassium Chloride 40-50meq were given daily for 5 weeks before baseline visit for testing. After baseline testing was completed, Allopurinol 300mg daily was added for 8-10 weeks. Serum uric acid (UA) levels were checked at study visit 2 weeks post baseline. If UA levels were above 5.0 an additional 300mg allopurinol was added with total dose of 600mg daily. The dosage of allopurinol then remained constant throughout the remainder of the study. Testing was repeated at 8-10 weeks after baseline.	B (Placebo) n=53 Participants Chlorthalidone 25 mg and Potassium Chloride 40-50meq were given daily for 5 weeks before baseline visit for testing. After baseline testing was completed, Placebo 300mg daily (identical in size, color, and dosage as allopurinol) was added for 8-10 weeks. Serum uric acid (UA) levels were checked at study visit 2 weeks post baseline. If UA levels were above 5.0 an additional 300mg placebo was added with total dose of 600mg daily. The dosage of placebo then remained constant throughout the remainder of the study. Testing was repeated at 8-10 weeks after baseline.
Change in Uric Acid (UA) Levels: Baseline Less End of Treatment	2.29 mg/dl Standard Deviation 1.29	0.14 mg/dl Standard Deviation 0.88

Adverse Events

A (Allopurinol)

Serious events: 4 serious events

Other events: 26 other events

Deaths: 0 deaths

B (Placebo)

Serious events: 3 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Measure	A (Allopurinol) n=71 participants at risk Chlorthalidone 25 mg and Potassium Chloride 40-50meq were given daily for 5 weeks before baseline visit for testing. After baseline testing was completed, Allopurinol 300mg daily was added for 8-10 weeks. Serum uric acid (UA) levels were checked at study visit 2 weeks post baseline. If UA levels were above 5.0 an additional 300mg allopurinol was added with total dose of 600mg daily. The dosage of allopurinol then remained constant throughout the remainder of the study. Testing was repeated at 8-10 weeks after baseline.	B (Placebo) n=71 participants at risk Chlorthalidone 25 mg and Potassium Chloride 40-50meq were given daily for 5 weeks before baseline visit for testing. After baseline testing was completed, Placebo 300mg daily (identical in size, color, and dosage as allopurinol) was added for 8-10 weeks. Serum uric acid (UA) levels were checked at study visit 2 weeks post baseline. If UA levels were above 5.0 an additional 300mg placebo was added with total dose of 600mg daily. The dosage of placebo then remained constant throughout the remainder of the study. Testing was repeated at 8-10 weeks after baseline.
Nervous system disorders Fatigue	0.00% 0/71 • Adverse event data were collected for 5 years, 1 month which represents the time the first consent was signed until the last subject completed participation in the study.	1.4% 1/71 • Number of events 1 • Adverse event data were collected for 5 years, 1 month which represents the time the first consent was signed until the last subject completed participation in the study.
Nervous system disorders Panic Attack	1.4% 1/71 • Number of events 1 • Adverse event data were collected for 5 years, 1 month which represents the time the first consent was signed until the last subject completed participation in the study.	0.00% 0/71 • Adverse event data were collected for 5 years, 1 month which represents the time the first consent was signed until the last subject completed participation in the study.
Cardiac disorders Chest Pain	1.4% 1/71 • Number of events 1 • Adverse event data were collected for 5 years, 1 month which represents the time the first consent was signed until the last subject completed participation in the study.	0.00% 0/71 • Adverse event data were collected for 5 years, 1 month which represents the time the first consent was signed until the last subject completed participation in the study.
Gastrointestinal disorders Nausea/Vomiting	0.00% 0/71 • Adverse event data were collected for 5 years, 1 month which represents the time the first consent was signed until the last subject completed participation in the study.	1.4% 1/71 • Number of events 1 • Adverse event data were collected for 5 years, 1 month which represents the time the first consent was signed until the last subject completed participation in the study.
Social circumstances Car Accident	1.4% 1/71 • Number of events 1 • Adverse event data were collected for 5 years, 1 month which represents the time the first consent was signed until the last subject completed participation in the study.	0.00% 0/71 • Adverse event data were collected for 5 years, 1 month which represents the time the first consent was signed until the last subject completed participation in the study.
Nervous system disorders Syncope	0.00% 0/71 • Adverse event data were collected for 5 years, 1 month which represents the time the first consent was signed until the last subject completed participation in the study.	1.4% 1/71 • Number of events 1 • Adverse event data were collected for 5 years, 1 month which represents the time the first consent was signed until the last subject completed participation in the study.
Skin and subcutaneous tissue disorders Rash	1.4% 1/71 • Number of events 1 • Adverse event data were collected for 5 years, 1 month which represents the time the first consent was signed until the last subject completed participation in the study.	0.00% 0/71 • Adverse event data were collected for 5 years, 1 month which represents the time the first consent was signed until the last subject completed participation in the study.

Other adverse events

Measure	A (Allopurinol) n=71 participants at risk Chlorthalidone 25 mg and Potassium Chloride 40-50meq were given daily for 5 weeks before baseline visit for testing. After baseline testing was completed, Allopurinol 300mg daily was added for 8-10 weeks. Serum uric acid (UA) levels were checked at study visit 2 weeks post baseline. If UA levels were above 5.0 an additional 300mg allopurinol was added with total dose of 600mg daily. The dosage of allopurinol then remained constant throughout the remainder of the study. Testing was repeated at 8-10 weeks after baseline.	B (Placebo) n=71 participants at risk Chlorthalidone 25 mg and Potassium Chloride 40-50meq were given daily for 5 weeks before baseline visit for testing. After baseline testing was completed, Placebo 300mg daily (identical in size, color, and dosage as allopurinol) was added for 8-10 weeks. Serum uric acid (UA) levels were checked at study visit 2 weeks post baseline. If UA levels were above 5.0 an additional 300mg placebo was added with total dose of 600mg daily. The dosage of placebo then remained constant throughout the remainder of the study. Testing was repeated at 8-10 weeks after baseline.
General disorders Headache	9.9% 7/71 • Number of events 7 • Adverse event data were collected for 5 years, 1 month which represents the time the first consent was signed until the last subject completed participation in the study.	8.5% 6/71 • Number of events 6 • Adverse event data were collected for 5 years, 1 month which represents the time the first consent was signed until the last subject completed participation in the study.
Musculoskeletal and connective tissue disorders Musculoskeletal pain/ache	12.7% 9/71 • Number of events 9 • Adverse event data were collected for 5 years, 1 month which represents the time the first consent was signed until the last subject completed participation in the study.	2.8% 2/71 • Number of events 3 • Adverse event data were collected for 5 years, 1 month which represents the time the first consent was signed until the last subject completed participation in the study.
Respiratory, thoracic and mediastinal disorders Cold	14.1% 10/71 • Number of events 10 • Adverse event data were collected for 5 years, 1 month which represents the time the first consent was signed until the last subject completed participation in the study.	4.2% 3/71 • Number of events 3 • Adverse event data were collected for 5 years, 1 month which represents the time the first consent was signed until the last subject completed participation in the study.

Additional Information

Mark S. Segal, MD, PhD; Assistant Professor and Chief, Division of Nephrology

University of Florida

Phone: 352-273-8821

Email: Mark.Segal@medicine.ufl.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place