Blood Pressure Effects of Nebivolol Versus Lisinopril in New Onset or Worsening Hypertension Induced by Bevacizumab

Comparative Blood Pressure Effects of Nebivolol Versus Lisinopril in Patients With New Onset or Exacerbated Hypertension Induced by Bevacizumab: a Crossover Study

The purpose of this study is to directly compare the blood pressure (hypertension) reduction effects of lisinopril and nebivolol in patients who develop new onset or worsening hypertension while treated with bevacizumab.

Study Overview

• Status: Withdrawn
• Conditions: Hypertension
• Intervention / Treatment: Drug: Nebivolol; Drug: Lisinopril

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients currently treated at the University of Mississippi Medical Center Oncology Clinic
• Patient is being treated with bevacizumab either alone or in combination with other agents for cancer
• Patient blood pressure is >140 mmHg (systolic) or > 90 mmHg (diastolic), either treated or untreated with medications for hypertension
• Patients may be currently on medications for hypertension (other than Beta blocker, ACEI, or ARB); these will be continued at the same dose throughout the study
• Patients should be > 18 years of age
• Patients receiving bevacizumab therapy approximately every 2 weeks

Exclusion Criteria:

• History of ACEI or ARB induced angioedema or idiopathic/hereditary angioedema
• Patient currently treated with a Beta blocker, ACEI, or ARB or have a history of intolerance to a medication in any of these classes
• Hyperkalemia, defined as a potassium value of >5 mEq/L
• Pregnancy or breastfeeding
• Severe renal impairment (eGFR <30 mL/min)
• Moderate hepatic impairment as identified by physician
• Currently taking CYP2D6 inducers (rifampin, carbamazepine or dexamethasone) or inhibitors (bupropion, fluoxetine, paroxetine, duloxetine, etc.)
• History of clinically significant EKG abnormality which would contraindicate beta blocker use
• Recent stroke (<6 months)
• Recent myocardial infarction (<6 months)
• Congestive heart failure
• Severe asthma or COPD
• Diagnosed obstructive sleep apnea

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Nebivolol; Nebivolol 5 mg daily for 2 weeks, then 5 or 10 mg daily for 2 weeks	Drug: Nebivolol; Nebivolol 5 or 10 mg tablets daily for 4 weeks. Lisinopril 20 or 40 mg daily for 4 weeks
Active Comparator: Lisinopril; 20 mg once daily for 2 weeks, then 20 or 40 mg once daily for 2 weeks	Drug: Lisinopril; Nebivolol 5 or 10 mg tablets daily for 4 weeks. Lisinopril 20 or 40 mg daily for 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary endpoint of the study will be changes in sitting systolic and diastolic blood pressure at the crossover and final visits.	Patients will be treated with both nebivolol or lisinopril for a period of 4 weeks, and then crossover to the opposite medication for an additional 4 weeks.	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The secondary endpoint of the study will be changes in heart rate at the end of the crossover and final visits.	Patients will be treated with both nebivolol or lisinopril for a period of 4 weeks, and then crossover to the opposite medication for an additional 4 weeks.	8 weeks

Collaborators and Investigators

• Sponsor: University of Mississippi Medical Center

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Anticipated): January 1, 2011
• Study Completion (Anticipated): August 1, 2011

Study Registration Dates

• First Submitted: February 24, 2010
• First Submitted That Met QC Criteria: February 24, 2010
• First Posted (Estimate): February 25, 2010

Study Record Updates

• Last Update Posted (Estimate): April 6, 2012
• Last Update Submitted That Met QC Criteria: April 5, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: Hypertension as a result of bevacizumab therapy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Enzyme Inhibitors; Protease Inhibitors; Protective Agents; Adrenergic Agonists; Cardiotonic Agents; Angiotensin-Converting Enzyme Inhibitors; Adrenergic beta-Agonists; Adrenergic beta-1 Receptor Agonists; Nebivolol; Lisinopril
• Other Study ID Numbers: 2009-0222