Study of the Effect of Intradialytic Vasopressin on Chronic Hypertension in Patients With End Stage Renal Disease

Pilot Study of the Effect of Intradialytic Vasopressin Infusion on Chronic Blood Pressure Control in Hypertensive Patients With End Stage Renal Disease: A Program to Develop a Decisive, Randomized Controlled Trial

The death rate of patients with endstage renal disease (ESRD) on dialysis each year is 20%, with diseases related to the heart and blood vessels causing about half. About 60% of patients on hemodialysis have high blood pressure, which is poorly controlled in most. Normal blood pressure in these patients greatly improves the chance of living. Increased fluid in the body and bloodstream is a major cause of hypertension in patients with ESRD. Fluid removal during hemodialysis is often limited by symptoms of low blood pressure during the procedure. Therefore the increase in fluid and related high blood pressure is ongoing for many of these patients. Arginine vasopressin (AVP) is a hormone naturally produced by the body which has little effect on blood pressure in healthy people, but acts as a powerful vasoconstrictor (narrows the blood vessels) when blood pressure is threatened. Recent studies have shown when there is too little AVP, patients are more likely to have low blood pressure during dialysis that limits fluid removal, an effect that can be reversed by giving these patients low doses of AVP. This phase II trial will find out which of two doses of AVP (.15 or .30 mU kg-1 min-1), in combination with standard therapy, works best to change interdialytic 44-hour ambulatory systolic blood pressure after 2 weeks. Patients who enroll in this study will be divided into three groups. One group will be given a 0.15 mU kg-1 min-1 dose of AVP at each dialysis session over a 2-week period; the second group will be given AVP 0.3 mU kg-1 min-1 at the same interval; and a third group will be given normal saline (placebo) at the same interval. All patients will be closely monitored for side-effects.

Study Overview

• Status: Completed
• Conditions: Hypertension; End Stage Renal Disease
• Intervention / Treatment: Drug: Vasopressin - Very Low Dose; Drug: Vasopressin - Low Dose; Drug: Placebo Comparator

Detailed Description

This pilot study originally enrolled a group of 12 subjects (4 subjects per arm) in order to demonstrate feasibility with the primary outcome measure, interdialytic 44-hour ambulatory systolic blood pressure. Data on the original subjects is complete and results are posted.

The data from this study will be used to design and conduct additional study enrollment/extension (24 subjects) in order to make some initial statistical comparisons between groups, which will help establish greater confidence in our novel method for controlling blood pressure in dialysis patients.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• End Stage Renal Disease on Hemodialysis greater than 3 months
• Hypertension (Predialysis systolic blood pressure (SBP) greater than 140 mmHg, averaged over preceding 6 dialysis treatments)
• Stable dry weight over preceding 6 dialysis treatments

Exclusion Criteria:

• Age less than 18 years
• Clinically significant vascular disease*
• Predialysis systolic blood pressure (SBP) greater than 200 mmHg or diastolic blood pressure (BP) >110
• Pregnancy
• Long QTc syndrome (an electrocardiogram (ECG) will be performed if unavailable within the last 3 months)

Clinically significant vascular disease is defined as any of the following occurring in the preceding three months: angina, claudication, transient ischemic attack, myocardial infarction, cerebrovascular accident, or decompensated heart failure. Furthermore, patients will be excluded if they have any history of ischemic colitis or Raynaud's disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group 1: Vasopressin - Very Low Dose; 0.15 mU per kg per minute	Drug: Vasopressin - Very Low Dose; Intradialytic vasopressin (AVP) infusion. The dose is calculated based upon the individual's weight in kilograms. A kilogram is equal to 2.2 pounds. For example, a person who weighs 70 kg (or 154 pounds) would receive a dose equal to 0.15 mU * 70 kg, or 10.5 mU of AVP per minute by infusion at their thrice-weekly dialysis treatments.; Other Names: Vasopressin Injection; USP (8-L arginine vasopressin); AVP; Pitressin®
Active Comparator: Group 2: Vasopressin - Low Dose; 0.30 mU per kg per minute	Drug: Vasopressin - Low Dose; Intradialytic vasopressin (AVP) infusion. The dose is calculated based upon the individual's weight in kilograms. A kilogram is equal to 2.2 pounds. For example, a person who weighs 70 kg (or 154 pounds) would receive a dose equal to 0.30 mU * 70 kg, or 21 mU of AVP per minute by infusion at their thrice-weekly dialysis treatments.; Other Names: Vasopressin Injection; USP (8-L arginine vasopressin); AVP; Pitressin®
Placebo Comparator: Group 3: Placebo; No Dose	Drug: Placebo Comparator; Participants in Group 3 will receive an equal volume of normal saline (placebo) infusion during their standard thrice-weekly dialysis treatments.; Other Names: Normal saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Mean Interdialytic 44-hour Ambulatory Systolic Blood Pressure Over a 2 Week Follow-up Period	This is designed to measure if the administration of intradialytic AVP will result in change in systolic blood pressure.	Baseline and Two Weeks

Collaborators and Investigators

• Sponsor: Columbia University
• Investigators: Principal Investigator: Anjali Ganda, M.D., M.S., Columbia University

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2010
• Primary Completion (Actual): August 1, 2018
• Study Completion (Actual): August 1, 2018

Study Registration Dates

• First Submitted: November 22, 2010
• First Submitted That Met QC Criteria: November 23, 2010
• First Posted (Estimate): November 24, 2010

Study Record Updates

• Last Update Posted (Actual): November 18, 2019
• Last Update Submitted That Met QC Criteria: October 31, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: hypertension; vasopressin; end stage renal disease; Arginine Vasopressin; AVP; Pitressin®
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Urologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Hypertension; Kidney Diseases; Kidney Failure, Chronic; Physiological Effects of Drugs; Natriuretic Agents; Hemostatics; Coagulants; Vasoconstrictor Agents; Antidiuretic Agents; Vasopressins; Arginine Vasopressin
• Other Study ID Numbers: AAAE0454 - pilot

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No