Trial Outcomes & Findings for Efficacy and Safety Study to Evaluate Combination Therapy With Nebivolol and Lisinopril vs. Placebo and Monotherapy in Patients With Stage 2 Diastolic Hypertension (NCT NCT01218100)
NCT ID: NCT01218100
Last Updated: 2012-06-21
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
664 participants
Primary outcome timeframe
Visit 6/(Week 0) and Visit 9/(Week 6)
Results posted on
2012-06-21
Participant Flow
664 patients were randomized to receive double-blind treatment; 661 patients received at least 1 dose of double-blind treatment (Safety Population); and 656 patients had at least 1 postbaseline assessment of trough seated DBP (ITT Population)
Participant milestones
| Measure |
Placebo
Placebo group - starting dose is placebo
|
Nebivolol + Lisinopril (Combination)
Combination group - starting dose level nebivolol 5mg and lisinopril 10mg
|
Nebivolol
Nebivolol monotherapy group - starting dose level nebivolol 5mg
|
Lisinopril
Lisinopril monotherapy group - starting dose level lisinopril 10mg
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
95
|
190
|
189
|
190
|
|
Overall Study
COMPLETED
|
71
|
165
|
162
|
156
|
|
Overall Study
NOT COMPLETED
|
24
|
25
|
27
|
34
|
Reasons for withdrawal
| Measure |
Placebo
Placebo group - starting dose is placebo
|
Nebivolol + Lisinopril (Combination)
Combination group - starting dose level nebivolol 5mg and lisinopril 10mg
|
Nebivolol
Nebivolol monotherapy group - starting dose level nebivolol 5mg
|
Lisinopril
Lisinopril monotherapy group - starting dose level lisinopril 10mg
|
|---|---|---|---|---|
|
Overall Study
Did not meet InclusionExclusion criteria
|
1
|
1
|
1
|
2
|
|
Overall Study
Adverse Event
|
4
|
6
|
6
|
7
|
|
Overall Study
Lack of Efficacy
|
9
|
6
|
5
|
12
|
|
Overall Study
Protocol Violation
|
0
|
0
|
1
|
1
|
|
Overall Study
Withdrawal by Subject
|
5
|
2
|
6
|
7
|
|
Overall Study
Lost to Follow-up
|
3
|
8
|
2
|
1
|
|
Overall Study
Other Reason
|
2
|
2
|
6
|
4
|
Baseline Characteristics
Efficacy and Safety Study to Evaluate Combination Therapy With Nebivolol and Lisinopril vs. Placebo and Monotherapy in Patients With Stage 2 Diastolic Hypertension
Baseline characteristics by cohort
| Measure |
Placebo
n=95 Participants
Placebo group - starting dose is placebo
|
Nebivolol + Lisinopril (Combination)
n=189 Participants
Combination group - starting dose level nebivolol 5mg and lisinopril 10mg
|
Nebivolol
n=188 Participants
Nebivolol monotherapy group - starting dose level nebivolol 5mg
|
Lisinopril
n=189 Participants
Lisinopril monotherapy group - starting dose level lisinopril 10mg
|
Total
n=661 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
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
95 Participants
n=5 Participants
|
189 Participants
n=7 Participants
|
188 Participants
n=5 Participants
|
189 Participants
n=4 Participants
|
661 Participants
n=21 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Age Continuous
|
47.4 years
STANDARD_DEVIATION 9.7 • n=5 Participants
|
48.8 years
STANDARD_DEVIATION 8.4 • n=7 Participants
|
49.7 years
STANDARD_DEVIATION 8.4 • n=5 Participants
|
50.1 years
STANDARD_DEVIATION 8 • n=4 Participants
|
49.2 years
STANDARD_DEVIATION 8.5 • n=21 Participants
|
|
Sex: Female, Male
Female
|
47 Participants
n=5 Participants
|
75 Participants
n=7 Participants
|
82 Participants
n=5 Participants
|
74 Participants
n=4 Participants
|
278 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
48 Participants
n=5 Participants
|
114 Participants
n=7 Participants
|
106 Participants
n=5 Participants
|
115 Participants
n=4 Participants
|
383 Participants
n=21 Participants
|
|
Region of Enrollment
United States
|
95 participants
n=5 Participants
|
189 participants
n=7 Participants
|
188 participants
n=5 Participants
|
189 participants
n=4 Participants
|
661 participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Visit 6/(Week 0) and Visit 9/(Week 6)Outcome measures
| Measure |
Placebo
n=93 Participants
Placebo group - starting dose is placebo
|
Nebivolol + Lisinopril (Combination)
n=189 Participants
Combination group - starting dose level nebivolol 5mg and lisinopril 10mg
|
Nebivolol
n=185 Participants
Nebivolol monotherapy group - starting dose level nebivolol 5mg
|
Lisinopril
n=189 Participants
Lisinopril monotherapy group - starting dose level lisinopril 10mg
|
|---|---|---|---|---|
|
The Change From Baseline in Trough Seated Diastolic Blood Pressure at Week 6.
|
-8.0 mm HG
Standard Deviation 9.2
|
-17.2 mm HG
Standard Deviation 10.2
|
-13.3 mm HG
Standard Deviation 8.9
|
-12.0 mm HG
Standard Deviation 9.8
|
SECONDARY outcome
Timeframe: Visit 6/(Week 0) and Visit 9/(Week 6)Outcome measures
| Measure |
Placebo
n=93 Participants
Placebo group - starting dose is placebo
|
Nebivolol + Lisinopril (Combination)
n=189 Participants
Combination group - starting dose level nebivolol 5mg and lisinopril 10mg
|
Nebivolol
n=185 Participants
Nebivolol monotherapy group - starting dose level nebivolol 5mg
|
Lisinopril
n=189 Participants
Lisinopril monotherapy group - starting dose level lisinopril 10mg
|
|---|---|---|---|---|
|
The Change From Baseline in Trough Seated Systolic Blood Pressure at Week 6.
|
-9.9 mm HG
Standard Deviation 16.4
|
-19.2 mm HG
Standard Deviation 19.8
|
-14.4 mm HG
Standard Deviation 14.1
|
-16.1 mm HG
Standard Deviation 17.2
|
Adverse Events
Placebo
Serious events: 2 serious events
Other events: 15 other events
Deaths: 0 deaths
Nebivolol + Lisinopril (Combination)
Serious events: 2 serious events
Other events: 31 other events
Deaths: 0 deaths
Nebivolol
Serious events: 3 serious events
Other events: 32 other events
Deaths: 0 deaths
Lisinopril
Serious events: 4 serious events
Other events: 24 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=95 participants at risk
Placebo group - starting dose is placebo
|
Nebivolol + Lisinopril (Combination)
n=189 participants at risk
Combination group - starting dose level nebivolol 5mg and lisinopril 10mg
|
Nebivolol
n=188 participants at risk
Nebivolol monotherapy group - starting dose level nebivolol 5mg
|
Lisinopril
n=189 participants at risk
Lisinopril monotherapy group - starting dose level lisinopril 10mg
|
|---|---|---|---|---|
|
Skin and subcutaneous tissue disorders
Angioedema
|
0.00%
0/95 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
0.00%
0/189 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
0.00%
0/188 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
0.53%
1/189 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
|
Vascular disorders
Cerebrovascular accident
|
0.00%
0/95 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
0.00%
0/189 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
0.00%
0/188 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
0.53%
1/189 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/95 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
0.00%
0/189 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
0.00%
0/188 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
0.53%
1/189 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
|
Gastrointestinal disorders
Pancreatitis acute
|
0.00%
0/95 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
0.00%
0/189 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
0.00%
0/188 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
0.53%
1/189 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
|
General disorders
Duodenal ulcer perforation
|
0.00%
0/95 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
0.53%
1/189 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
0.00%
0/188 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
0.00%
0/189 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.00%
0/95 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
0.53%
1/189 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
0.00%
0/188 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
0.00%
0/189 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.00%
0/95 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
0.53%
1/189 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
0.53%
1/188 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
0.00%
0/189 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
|
Renal and urinary disorders
Urinary tract infection
|
0.00%
0/95 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
0.53%
1/189 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
0.00%
0/188 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
0.00%
0/189 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
|
Psychiatric disorders
Anxiety
|
1.1%
1/95 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
0.00%
0/189 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
0.00%
0/188 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
0.00%
0/189 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
|
General disorders
Chest pain
|
1.1%
1/95 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
0.00%
0/189 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
0.00%
0/188 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
0.00%
0/189 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
|
Vascular disorders
Hypertension
|
1.1%
1/95 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
0.00%
0/189 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
0.00%
0/188 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
0.00%
0/189 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.00%
0/95 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
0.00%
0/189 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
0.53%
1/188 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
0.00%
0/189 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
0.00%
0/95 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
0.00%
0/189 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
0.53%
1/188 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
0.00%
0/189 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
|
General disorders
Pyrexia
|
0.00%
0/95 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
0.00%
0/189 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
0.53%
1/188 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
0.00%
0/189 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
|
Cardiac disorders
Syncope
|
1.1%
1/95 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
0.00%
0/189 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
0.00%
0/188 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
0.00%
0/189 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Throat cancer
|
1.1%
1/95 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
0.00%
0/189 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
0.00%
0/188 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
0.00%
0/189 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
Other adverse events
| Measure |
Placebo
n=95 participants at risk
Placebo group - starting dose is placebo
|
Nebivolol + Lisinopril (Combination)
n=189 participants at risk
Combination group - starting dose level nebivolol 5mg and lisinopril 10mg
|
Nebivolol
n=188 participants at risk
Nebivolol monotherapy group - starting dose level nebivolol 5mg
|
Lisinopril
n=189 participants at risk
Lisinopril monotherapy group - starting dose level lisinopril 10mg
|
|---|---|---|---|---|
|
Infections and infestations
Upper respiratory tract infection
|
4.2%
4/95 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
6.9%
13/189 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
5.9%
11/188 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
4.2%
8/189 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
|
Infections and infestations
Nasopharyngitis
|
4.2%
4/95 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
5.3%
10/189 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
6.4%
12/188 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
5.3%
10/189 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
|
Nervous system disorders
Headache
|
8.4%
8/95 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
4.8%
9/189 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
5.3%
10/188 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
4.2%
8/189 • Adverse event reporting occurred from October 6th, 2010 to May 18th, 2011.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee All data generated in this study will be the property of Forest Research Institute, Inc. An integrated clinical and statistical report will be prepared at the completion of the study. Publication of the results by the Investigator will be subject to mutual agreement between the Investigator and Forest Research Institute, Inc.
- Publication restrictions are in place
Restriction type: OTHER