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

• ClinicalTrials.gov Identifier: NCT01247090
• Recruitment Status: Completed
• First Posted: November 24, 2010
• Results First Posted: April 28, 2011
• Last Update Posted: November 18, 2019
• Sponsor: Columbia University
• Information provided by (Responsible Party): Columbia University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Hypertension; End Stage Renal Disease	Drug: Vasopressin - Very Low Dose; Drug: Vasopressin - Low Dose; Drug: Placebo Comparator	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: October 2010
• Actual Primary Completion Date: August 2018
• Actual Study Completion Date: August 2018

Arms and Interventions

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 Name: Normal saline

Outcome Measures

Primary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, New York

Columbia University Medical Center

New York, New York, United States, 10032

Sponsors and Collaborators

Columbia University

Investigators

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

  Study Documents (Full-Text)

Documents provided by Columbia University:

Study Protocol and Statistical Analysis Plan  [PDF] September 27, 2016

More Information

• Responsible Party: Columbia University
• ClinicalTrials.gov Identifier: NCT01247090
• Other Study ID Numbers: AAAE0454 - pilot
• First Posted: November 24, 2010
• Results First Posted: April 28, 2011
• Last Update Posted: November 18, 2019
• Last Verified: October 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Columbia University:

hypertension; end stage renal disease; vasopressin; Arginine Vasopressin; AVP; Pitressin®

Additional relevant MeSH terms:

Kidney Diseases; Kidney Failure, Chronic; Hypertension; Vascular Diseases; Cardiovascular Diseases; Urologic Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Vasopressins; Arginine Vasopressin; Hemostatics; Coagulants; Vasoconstrictor Agents; Antidiuretic Agents; Natriuretic Agents; Physiological Effects of Drugs