Trial Outcomes & Findings for Pharmacogenomic Evaluation of Antihypertensive Responses 2 (NCT NCT01203852)
NCT ID: NCT01203852
Last Updated: 2018-04-06
Results Overview
Response to blood pressure medication will be assessed by measuring blood pressure before and after treatment
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
839 participants
Primary outcome timeframe
after 6-8 weeks of treatment
Results posted on
2018-04-06
Participant Flow
The first subject was recruited on 8/10/10 and the final patient was recruited on 9/30/2013. Subjects were recruited from family medicine clinics and were identified through providers daily schedules, medical records, and encounter forms.
Healthy volunteers with mild to moderate primary hypertension between the ages of 18-70 were eligible for the study. Subjects were washed-out from their hypertension medication prior to beginning study protocol. Participants with elevated systolic blood pressure greater than 180 mmHg after wash-out were excluded from the study.
Participant milestones
| Measure |
Metoprolol + Chlorthalidone
This group was assigned the following:
(Metoprolol 8 weeks): Metoprolol tartrate 50 mg twice daily for two weeks. After two weeks subjects will be seen in clinic and will have the dose doubled to 100 mg twice daily if either their home blood pressure (HBP) average or office blood pressure (OBP) is \> 120/70 mmHg. They will continue on this dose for an additional 6 weeks.
(Washout 2 weeks): Then will washout from all study medication.
(Chlorthalidone 8 weeks): participants will initiate chlorthalidone 25 mg four times per week (Monday, Wednesday, Thursday, Saturday) for two weeks, then 25 mg daily of chlorthalidone for 6 weeks.
|
|---|---|
|
Metoprolol 8 Weeks
STARTED
|
839
|
|
Metoprolol 8 Weeks
COMPLETED
|
369
|
|
Metoprolol 8 Weeks
NOT COMPLETED
|
470
|
|
Washout 2 Weeks
STARTED
|
328
|
|
Washout 2 Weeks
COMPLETED
|
282
|
|
Washout 2 Weeks
NOT COMPLETED
|
46
|
|
Chlorthalidone 8 Weeks
STARTED
|
328
|
|
Chlorthalidone 8 Weeks
Continued From Metoprolol
|
282
|
|
Chlorthalidone 8 Weeks
COMPLETED
|
328
|
|
Chlorthalidone 8 Weeks
NOT COMPLETED
|
0
|
Reasons for withdrawal
| Measure |
Metoprolol + Chlorthalidone
This group was assigned the following:
(Metoprolol 8 weeks): Metoprolol tartrate 50 mg twice daily for two weeks. After two weeks subjects will be seen in clinic and will have the dose doubled to 100 mg twice daily if either their home blood pressure (HBP) average or office blood pressure (OBP) is \> 120/70 mmHg. They will continue on this dose for an additional 6 weeks.
(Washout 2 weeks): Then will washout from all study medication.
(Chlorthalidone 8 weeks): participants will initiate chlorthalidone 25 mg four times per week (Monday, Wednesday, Thursday, Saturday) for two weeks, then 25 mg daily of chlorthalidone for 6 weeks.
|
|---|---|
|
Metoprolol 8 Weeks
Physician Decision
|
470
|
|
Washout 2 Weeks
Physician Decision
|
46
|
Baseline Characteristics
Pharmacogenomic Evaluation of Antihypertensive Responses 2
Baseline characteristics by cohort
| Measure |
Metoprolol + Chlorthalidone
n=839 Participants
This group was assigned to the following: Metoprolol tartrate 50 mg twice daily for two weeks. After two weeks subjects will be seen in clinic and will have the dose doubled to 100 mg twice daily if either their HBP average or OBP is \> 120/70 mmHg. They will continue on this dose for an additional 6 weeks. Then will washout from all study medication. After washout, participants will initiate chlorthalidone 25 mg four times per week (Monday, Wednesday, Thursday, Saturday) for two weeks, then 25 mg daily of chlorthalidone for 6 weeks.
Metoprolol: Metoprolol 50 mg twice daily titrated to 100 mg twice daily
Chlorthalidone: Chlorthalidone 25 mg 4 times per week titrated to 25 mg daily
Note: due to discontinuation of the manufacture of chlorthalidone 15 mg, effective Jan 1, 2013; the starting dose of chlorthalidone will be 25 mg 4 times per week (Mon, Wed, Thur, Sat) with subsequent titration to 25 mg daily.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
839 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
50.3 years
STANDARD_DEVIATION 9.0 • n=5 Participants
|
|
Sex: Female, Male
Female
|
429 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
410 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
839 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: after 6-8 weeks of treatmentPopulation: All patients with antihypertensive response data. 282 patients completed all 3 study periods. 369 patients completed only period 1. 328 patients completed only period 3.
Response to blood pressure medication will be assessed by measuring blood pressure before and after treatment
Outcome measures
| Measure |
Metoprolol + Chlorthalidone
n=282 Participants
Study participants had their current hypertension treatment withdrawn, baseline labs drawn and hypertension documented. Participants were initiated on metoprolol tartrate 50 mg twice daily for two weeks, followed by dose titration to 100 mg twice daily for six additional weeks if blood pressure (BP) \> 120/70 mmHg. BP measures were again recorded. Participants entered a washout where metoprolol was titrated, then discontinued, and the patient's hypertension was re-established. After another set of identical baseline labs, study participants were initiated on chlorthalidone 25 mg four days per week (Monday, Wednesday, Thursday, Saturday) 15 mg daily for two weeks, followed by 25 mg daily for an additional six weeks.
|
Metorprolol Only
n=369 Participants
Study participants had their current hypertension treatment withdrawn, baseline labs drawn and hypertension documented. Participants were initiated on metoprolol tartrate 50 mg twice daily for two weeks, followed by dose titration to 100 mg twice daily for six additional weeks if blood pressure (BP) \> 120/70 mmHg. BP measures were again recorded.
|
Chlorthalidone Only
n=328 Participants
Study participants were initiated on chlorthalidone 25 mg four days per week (Monday, Wednesday, Thursday, Saturday) 15 mg daily for two weeks, followed by 25 mg daily for an additional six weeks.
|
|---|---|---|---|
|
Change in Blood Pressure From Baseline to Treatment
diastolic blood pressure response
|
-7.56 mmHg
Standard Deviation 6.39
|
-7.97 mmHg
Standard Deviation 6.48
|
-7.68 mmHg
Standard Deviation 5.84
|
|
Change in Blood Pressure From Baseline to Treatment
systolic blood pressure response
|
-11.70 mmHg
Standard Deviation 9.51
|
-7.45 mmHg
Standard Deviation 9.85
|
-13.65 mmHg
Standard Deviation 9.55
|
SECONDARY outcome
Timeframe: after 6-8 weeks treatmentPopulation: All patients with change in glucose data
Change in glucose after treatment with study medication
Outcome measures
| Measure |
Metoprolol + Chlorthalidone
n=365 Participants
Study participants had their current hypertension treatment withdrawn, baseline labs drawn and hypertension documented. Participants were initiated on metoprolol tartrate 50 mg twice daily for two weeks, followed by dose titration to 100 mg twice daily for six additional weeks if blood pressure (BP) \> 120/70 mmHg. BP measures were again recorded. Participants entered a washout where metoprolol was titrated, then discontinued, and the patient's hypertension was re-established. After another set of identical baseline labs, study participants were initiated on chlorthalidone 25 mg four days per week (Monday, Wednesday, Thursday, Saturday) 15 mg daily for two weeks, followed by 25 mg daily for an additional six weeks.
|
Metorprolol Only
Study participants had their current hypertension treatment withdrawn, baseline labs drawn and hypertension documented. Participants were initiated on metoprolol tartrate 50 mg twice daily for two weeks, followed by dose titration to 100 mg twice daily for six additional weeks if blood pressure (BP) \> 120/70 mmHg. BP measures were again recorded.
|
Chlorthalidone Only
Study participants were initiated on chlorthalidone 25 mg four days per week (Monday, Wednesday, Thursday, Saturday) 15 mg daily for two weeks, followed by 25 mg daily for an additional six weeks.
|
|---|---|---|---|
|
Adverse Metabolic Effects
glucose response to metoprolol (n=365)
|
1.02 mg/dL
Standard Deviation 9.83
|
—
|
—
|
|
Adverse Metabolic Effects
glucose response to chlorthalidone (n=318)
|
5.12 mg/dL
Standard Deviation 10.6
|
—
|
—
|
Adverse Events
All Study Participants
Serious events: 3 serious events
Other events: 114 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
All Study Participants
n=839 participants at risk
Study participants had their current hypertension treatment withdrawn, baseline labs drawn and hypertension documented. Participants were initiated on metoprolol tartrate 50 mg twice daily for two weeks, followed by dose titration to 100 mg twice daily for six additional weeks if blood pressure (BP) \> 120/70 mmHg. BP measures were again recorded. Participants entered a washout where metoprolol was titrated, then discontinued, and the patient's hypertension was re-established. The subjects were initiated on chlorthalidone 25 mg four days per week (Monday, Wednesday, Thursday, Saturday) 15 mg daily for two weeks, followed by 25 mg daily for an additional six weeks.
|
|---|---|
|
Vascular disorders
Headache
|
0.24%
2/839 • Number of events 2 • Adverse events were recorded during subject participation in the study. Participation lasted between 3 and 4 months.
Adverse events were not recorded according to intervention.
|
|
Cardiac disorders
Heart Attack
|
0.12%
1/839 • Number of events 1 • Adverse events were recorded during subject participation in the study. Participation lasted between 3 and 4 months.
Adverse events were not recorded according to intervention.
|
Other adverse events
| Measure |
All Study Participants
n=839 participants at risk
Study participants had their current hypertension treatment withdrawn, baseline labs drawn and hypertension documented. Participants were initiated on metoprolol tartrate 50 mg twice daily for two weeks, followed by dose titration to 100 mg twice daily for six additional weeks if blood pressure (BP) \> 120/70 mmHg. BP measures were again recorded. Participants entered a washout where metoprolol was titrated, then discontinued, and the patient's hypertension was re-established. The subjects were initiated on chlorthalidone 25 mg four days per week (Monday, Wednesday, Thursday, Saturday) 15 mg daily for two weeks, followed by 25 mg daily for an additional six weeks.
|
|---|---|
|
Cardiac disorders
Bradycardia
|
0.24%
2/839 • Number of events 2 • Adverse events were recorded during subject participation in the study. Participation lasted between 3 and 4 months.
Adverse events were not recorded according to intervention.
|
|
Cardiac disorders
Chest Pain
|
0.24%
2/839 • Number of events 2 • Adverse events were recorded during subject participation in the study. Participation lasted between 3 and 4 months.
Adverse events were not recorded according to intervention.
|
|
Gastrointestinal disorders
Diarrhea
|
0.48%
4/839 • Number of events 4 • Adverse events were recorded during subject participation in the study. Participation lasted between 3 and 4 months.
Adverse events were not recorded according to intervention.
|
|
Ear and labyrinth disorders
Dizziness
|
1.2%
10/839 • Number of events 11 • Adverse events were recorded during subject participation in the study. Participation lasted between 3 and 4 months.
Adverse events were not recorded according to intervention.
|
|
Nervous system disorders
Dyspnea
|
0.12%
1/839 • Number of events 1 • Adverse events were recorded during subject participation in the study. Participation lasted between 3 and 4 months.
Adverse events were not recorded according to intervention.
|
|
Vascular disorders
Headache
|
3.5%
29/839 • Number of events 32 • Adverse events were recorded during subject participation in the study. Participation lasted between 3 and 4 months.
Adverse events were not recorded according to intervention.
|
|
Gastrointestinal disorders
Nausea
|
0.83%
7/839 • Number of events 8 • Adverse events were recorded during subject participation in the study. Participation lasted between 3 and 4 months.
Adverse events were not recorded according to intervention.
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.36%
3/839 • Number of events 3 • Adverse events were recorded during subject participation in the study. Participation lasted between 3 and 4 months.
Adverse events were not recorded according to intervention.
|
|
General disorders
Fatigue
|
1.8%
15/839 • Number of events 16 • Adverse events were recorded during subject participation in the study. Participation lasted between 3 and 4 months.
Adverse events were not recorded according to intervention.
|
|
General disorders
Other
|
4.9%
41/839 • Number of events 55 • Adverse events were recorded during subject participation in the study. Participation lasted between 3 and 4 months.
Adverse events were not recorded according to intervention.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place