The Effects of Renin Inhibition on Fibrinolytic Balance and Endothelial Function

NCT03115853 | Completed Phase 4 Results

• 1 other identifier: 090738
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

Aliskiren (also called TekturnaTM) is a new drug for high blood pressure. Aliskiren works by blocking the actions of a substance called renin. Renin is a natural substance in the body that raises blood pressure. Renin is believed to contribute to the production of blood clots by increasing the amount of a substance known as Plasminogen Activator Inhibitor or PAI-1. This study will measure how aliskiren changes the amount of PAI-1 in the blood depending on the time of dosing. The purpose of this study is to find out if it is better to take aliskiren in the morning or at night.

Conditions

High Blood Pressure

Outcome Measures

Primary Outcomes (2)

• Difference in Peak Plasma PAI-1 Level

  baseline to 18 weeks

• Difference in Mean Plasma PAI-1 Level

  baseline to 18 weeks

Secondary Outcomes (3)

• Difference in Mean Plasma Aldosterone Levels

  baseline to 18 weeks

• Difference in Mean Changes in Plasma Renin Activity.

  baseline to 18 weeks

• Difference in Mean Plasma Peak Aldosterone Levels

  baseline to 18 weeks

Study Arms (2)

HCTZ plus Aliskiren then HCTZ and Placebo

EXPERIMENTAL

HCTZ 25 mg plus Aliskiren 150mg for 2weeks. Aliskiren is increased to 300mg for 4 week if 150mg was tolerated. Then HCTZ 25 mg po plus Placebo

Drug: Aliskiren 150 mg; Drug: Placebo; Drug: HCTZ; Drug: Aliskiren 300 mg

HCTZ and Placebo, then HCTZ and Aliskiren

EXPERIMENTAL

HCTZ 25 mg po plus Placebo. Then HCTZ 25 mg plus Aliskiren 150mg for 2weeks. Aliskiren is increased to 300mg for 4 week if 150mg was tolerated.

Drug: Aliskiren 150 mg; Drug: Placebo; Drug: HCTZ; Drug: Aliskiren 300 mg

Interventions

Aliskiren 150 mg DRUG

Aliskiren 150 mg daily for 2 weeks

Also known as: Tekturna

HCTZ and Placebo, then HCTZ and Aliskiren; HCTZ plus Aliskiren then HCTZ and Placebo

Placebo DRUG

Placebo tablet for Aliskerin

HCTZ and Placebo, then HCTZ and Aliskiren; HCTZ plus Aliskiren then HCTZ and Placebo

HCTZ DRUG

HCTZ 25mg every day for 18 weeks

HCTZ and Placebo, then HCTZ and Aliskiren; HCTZ plus Aliskiren then HCTZ and Placebo

Aliskiren 300 mg DRUG

Aliskiren 300 mg for 4 weeks

HCTZ and Placebo, then HCTZ and Aliskiren; HCTZ plus Aliskiren then HCTZ and Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults 18-65 with hypertension
• Hypertension is defined as a systolic blood pressure at screening of ≥ 140, a diastolic blood pressure of ≥ 90, or a preexisting diagnosis of hypertension taking antihypertensive medication. If the subject is on anti-hypertensive medication, they can be included in the study, independent of the screening blood pressure.

You may not qualify if:

• Serum potassium \> 5.0 mmol/L (at the visit directly preceding Randomization)
• History of any cardiovascular event (stroke, TIA, MI, unstable angina, CABG, percutaneous coronary intervention, hospitalization due to HF) during the 3 months prior to Visit 1 or subsequent to enrollment.
• Malignant Hypertension (at Randomization): any patient with SBP \> 170 mmHg or DBP \> 120 mmHg
• Congestive heart failure NYHA class III and IV
• Unstable serum creatinine
• Second (II) or third (III) degree heart block without a pacemaker.
• Concurrent potentially life threatening arrhythmia or other uncontrolled arrhythmia.
• Clinically significant valvular heart disease.
• Known renal artery stenosis.
• Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of the study drugs including, but not limited to, any of the following:
• History of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection (patients with previous bariatric surgery \> 6 months prior to Visit 1 are allowed to participate).
• Any history of pancreatic injury, pancreatitis or evidence of impaired pancreatic function/injury as indicated by abnormal lipase or amylase.
• Evidence of hepatic disease as determined by any one of the following: SGPT value exceeding 3 x Upper Limit of Normal (ULN) at Visit 1, a history of hepatic encephalopathy, a history of cirrhosis, esophageal varices, or a history of portocaval shunt.
• History of malignancy other than basal cell skin cancer within the past five years.
• Any concurrent life threatening condition with a life expectancy less than 2 years.

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

VUMC

Nashville, Tennessee, United States

Location

MeSH Terms

Conditions

Hypertension

Interventions

aliskiren; Hydrochlorothiazide

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Chlorothiazide; Benzothiadiazines; Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Thiazides; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: James Muldowney, MD
• Organization: Vanderbilt University Medical Center

james.muldowney@vanderbilt.edu

615-936-1720

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Director

Study Record Dates

• First Submitted: March 16, 2017
• First Posted: April 14, 2017
• Study Start: June 1, 2009
• Primary Completion: January 1, 2012
• Study Completion: January 1, 2012
• Last Updated: August 25, 2017
• Results First Posted: August 25, 2017

Record last verified: 2017-07

Locations

US (1)