Trial Outcomes & Findings for Nebivolol in the Supine Hypertension of Autonomic Failure (NCT NCT01044693)

NCT ID: NCT01044693

Last Updated: 2015-05-01

Results Overview

Maximal change from baseline in systolic blood pressure, measured from 8 pm to 8 am, after a single dose of the intervention

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 20 participants
• Primary outcome timeframe: 8 pm - 8 am
• Results posted on: 2015-05-01

Participant Flow

Participant milestones

Measure	Placebo Then Metoprolol Then Sildenafil Then Nebivolol Single oral dose of: metoprolol tartrate 50 mg, sildenafil 25 mg, nebivolol 5 mg	Placebo Then Nebivolol Then Metoprolol Then Sildenafil Single oral dose of: metoprolol tartrate 50 mg, sildenafil 25 mg, nebivolol 5 mg	Placebo Then Sildenafil Then Nebivolol Then Metoprolol Single oral dose of: metoprolol tartrate 50 mg, sildenafil 25 mg, nebivolol 5 mg	Placebo Then Sildenafil Then Metoprolol Then Nebivolol Single oral dose of: metoprolol tartrate 50 mg, sildenafil 25 mg, nebivolol 5 mg	Nebivolol Then Placebo Then Metoprolol Then Sildenafil Single oral dose of: metoprolol tartrate 50 mg, sildenafil 25 mg, nebivolol 5 mg	Metoprolol Then Sildenafil Then Placebo Then Nebivolol Single oral dose of: metoprolol tartrate 50 mg, sildenafil 25 mg, nebivolol 5 mg	Sildenafil Then Nebivolol Then Placebo Then Metoprolol Single oral dose of: metoprolol tartrate 50 mg, sildenafil 25 mg, nebivolol 5 mg	Metoprolol Then Placebo Then Nebivolol Then Sildenafil Single oral dose of: metoprolol tartrate 50 mg, sildenafil 25 mg, nebivolol 5 mg	Nebivolol Then Metoprolol Then Sildenafil Then Placebo Single oral dose of: metoprolol tartrate 50 mg, sildenafil 25 mg, nebivolol 5 mg	Metoprolol Then Nebivolol Then Placebo Then Sildenafil Single oral dose of: metoprolol tartrate 50 mg, sildenafil 25 mg, nebivolol 5 mg	Metoprolol Then Sildenafil Then Nebivolol Then Placebo Single oral dose of: metoprolol tartrate 50 mg, sildenafil 25 mg, nebivolol 5 mg	Sildenafil Then Nebivolol Then Metoprolol Then Placebo Single oral dose of: metoprolol tartrate 50 mg, sildenafil 25 mg, nebivolol 5 mg	Sildenafil Then Metoprolol Then Nebivolol Then Placebo Single oral dose of: metoprolol tartrate 50 mg, sildenafil 25 mg, nebivolol 5 mg	Nebivolol Then Sildenafil Then Metoprolol Then Placebo Single oral dose of: metoprolol tartrate 50 mg, sildenafil 25 mg, nebivolol 5 mg	Nebivolol Then Placebo Then Sildenafil Then Metoprolol Single oral dose of: metoprolol tartrate 50 mg, sildenafil 25 mg, nebivolol 5 mg	Placebo Then Nebivolol Then Sildenafil Then Metoprolol Single oral dose of: metoprolol tartrate 50 mg, sildenafil 25 mg, nebivolol 5 mg
Overall Study STARTED	3	1	1	1	1	2	1	1	1	1	1	1	2	1	1	1
Overall Study COMPLETED	3	1	1	1	1	2	1	1	1	1	1	1	2	1	1	1
Overall Study NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Nebivolol in the Supine Hypertension of Autonomic Failure

Baseline characteristics by cohort

Measure	All Study Participants n=20 Participants Participants who were randomized to receive placebo, metoprolol, sildenafil and nebivolol in any order
Age, Continuous	69 years STANDARD_DEVIATION 8 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants
BMI	25.6 kg/m2 STANDARD_DEVIATION 3.2 • n=5 Participants
Duration of disease	8 years STANDARD_DEVIATION 6 • n=5 Participants
Diagnosis Pure autonomic failure	10 participants n=5 Participants
Diagnosis Parkinson Disease with autonomic failure	4 participants n=5 Participants
Diagnosis Multiple System Atrophy	6 participants n=5 Participants
Medical history of essential hypertension yes	4 participants n=5 Participants
Medical history of essential hypertension No	16 participants n=5 Participants
Systolic BP, supine	169 mm Hg STANDARD_DEVIATION 24 • n=5 Participants
Systolic BP, upright	83 mm Hg STANDARD_DEVIATION 25 • n=5 Participants
Heart rate, supine	68 bpm STANDARD_DEVIATION 10 • n=5 Participants
Heart rate, upright	83 bpm STANDARD_DEVIATION 15 • n=5 Participants
Plasma norepinephrine, supine	136 pg/mL STANDARD_DEVIATION 98 • n=5 Participants
Plasma norepinephrine, upright	253 pg/mL STANDARD_DEVIATION 209 • n=5 Participants

PRIMARY outcome

Timeframe: 8 pm - 8 am

Population: Participants who completed the 4 treatment arms

Maximal change from baseline in systolic blood pressure, measured from 8 pm to 8 am, after a single dose of the intervention

Outcome measures

Measure	Placebo Capsule n=20 Participants Placebo capsule Placebo: Placebo capsule	Nebivolol 5 mg n=20 Participants Nebivolol 5 mg capsule Nebivolol 5 mg: Nebivolol 5mg single oral dose	Metoprolol Tartrate 50 mg n=20 Participants Metoprolol tartrate 50 mg single oral dose metoprolol tartrate 50 mg: metoprolol tartrate 50 mg single oral dose	Sildenafil 25 mg n=20 Participants Sildenafil 25 mg single oral dose Sildenafil25 mg: Sildenafil 25 mg single oral dose
Change in Systolic Blood Pressure During the Night Change in systolic BP	1 mm Hg Standard Error 7	-24 mm Hg Standard Error 9	-7 mm Hg Standard Error 6	-20 mm Hg Standard Error 6
Change in Systolic Blood Pressure During the Night Baseline supine at 8 pm	154 mm Hg Standard Error 7	162 mm Hg Standard Error 5	157 mm Hg Standard Error 5	158 mm Hg Standard Error 6

SECONDARY outcome

Timeframe: 8 pm - 8 am

Population: Participants with complete urine collections during the 4 study nights

Nocturnal sodium excretion was defined as the ratio of urinary sodium to urinary creatinine.

Outcome measures

Measure	Placebo Capsule n=14 Participants Placebo capsule Placebo: Placebo capsule	Nebivolol 5 mg n=14 Participants Nebivolol 5 mg capsule Nebivolol 5 mg: Nebivolol 5mg single oral dose	Metoprolol Tartrate 50 mg n=14 Participants Metoprolol tartrate 50 mg single oral dose metoprolol tartrate 50 mg: metoprolol tartrate 50 mg single oral dose	Sildenafil 25 mg n=14 Participants Sildenafil 25 mg single oral dose Sildenafil25 mg: Sildenafil 25 mg single oral dose
Nocturnal Urinary Sodium Excretion	0.145 mEq/mg Standard Error 0.015	0.127 mEq/mg Standard Error 0.011	0.139 mEq/mg Standard Error 0.019	0.125 mEq/mg Standard Error 0.018

SECONDARY outcome

Timeframe: 10 min standing

Population: Comparisons were made only for patients who could stand after all treatment groups

Orthostatic tolerance was defined as the area under the curve of standing systolic blood pressure calculated by the trapezoidal rule (upright systolic blood pressure multiplied by standing time) during a 10-minute standing test

Outcome measures

Measure	Placebo Capsule n=11 Participants Placebo capsule Placebo: Placebo capsule	Nebivolol 5 mg n=11 Participants Nebivolol 5 mg capsule Nebivolol 5 mg: Nebivolol 5mg single oral dose	Metoprolol Tartrate 50 mg n=11 Participants Metoprolol tartrate 50 mg single oral dose metoprolol tartrate 50 mg: metoprolol tartrate 50 mg single oral dose	Sildenafil 25 mg n=11 Participants Sildenafil 25 mg single oral dose Sildenafil25 mg: Sildenafil 25 mg single oral dose
Orthostatic Tolerance the Following Morning	594 mm Hg*min Standard Error 108	675 mm Hg*min Standard Error 113	696 mm Hg*min Standard Error 128	575 mm Hg*min Standard Error 106

SECONDARY outcome

Timeframe: 8 pm - 8 am

Population: Participants who completed the 4 treatment arms

Change from baseline (8 pm) in heart rate at the time of maximal BP-lowering effect

Outcome measures

Measure	Placebo Capsule n=20 Participants Placebo capsule Placebo: Placebo capsule	Nebivolol 5 mg n=20 Participants Nebivolol 5 mg capsule Nebivolol 5 mg: Nebivolol 5mg single oral dose	Metoprolol Tartrate 50 mg n=20 Participants Metoprolol tartrate 50 mg single oral dose metoprolol tartrate 50 mg: metoprolol tartrate 50 mg single oral dose	Sildenafil 25 mg n=20 Participants Sildenafil 25 mg single oral dose Sildenafil25 mg: Sildenafil 25 mg single oral dose
Change in Heart Rate During the Night	-3 bpm Standard Error 2	-6 bpm Standard Error 2	-6 bpm Standard Error 2	0 bpm Standard Error 2

Adverse Events

Placebo Capsule

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Nebivolol 5 mg

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Metoprolol Tartrate 50 mg

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Sildenafil 25 mg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Placebo Capsule n=20 participants at risk Placebo capsule Placebo: Placebo capsule	Nebivolol 5 mg n=20 participants at risk Nebivolol 5 mg capsule Nebivolol 5 mg: Nebivolol 5mg single oral dose	Metoprolol Tartrate 50 mg n=20 participants at risk Metoprolol tartrate 50 mg single oral dose metoprolol tartrate 50 mg: metoprolol tartrate 50 mg single oral dose	Sildenafil 25 mg n=20 participants at risk Sildenafil 25 mg single oral dose Sildenafil25 mg: Sildenafil 25 mg single oral dose
Nervous system disorders fall	0.00% 0/20 • 1 day for each intervention Safety population included all participants	0.00% 0/20 • 1 day for each intervention Safety population included all participants	0.00% 0/20 • 1 day for each intervention Safety population included all participants	5.0% 1/20 • Number of events 1 • 1 day for each intervention Safety population included all participants
Renal and urinary disorders Urinary Tract Infection and diarrhea	0.00% 0/20 • 1 day for each intervention Safety population included all participants	0.00% 0/20 • 1 day for each intervention Safety population included all participants	0.00% 0/20 • 1 day for each intervention Safety population included all participants	5.0% 1/20 • Number of events 1 • 1 day for each intervention Safety population included all participants

Additional Information

Italo Biaggioni MD

Vanderbilt University

Phone: 615-936-3420

Email: italo.biaggioni@vanderbilt.edu

Results disclosure agreements

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