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

NCT01247090 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: AAAE0454 - pilot
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Hypertension; End Stage Renal Disease

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (3)

Group 1: Vasopressin - Very Low Dose

ACTIVE COMPARATOR

0.15 mU per kg per minute

Drug: Vasopressin - Very Low Dose

Group 2: Vasopressin - Low Dose

ACTIVE COMPARATOR

0.30 mU per kg per minute

Drug: Vasopressin - Low Dose

Group 3: Placebo

PLACEBO COMPARATOR

No Dose

Drug: Placebo Comparator

Interventions

Vasopressin - Very Low Dose DRUG

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.

Also known as: Vasopressin Injection, USP (8-L arginine vasopressin), AVP, Pitressin®

Group 1: Vasopressin - Very Low Dose

Vasopressin - Low Dose DRUG

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.

Also known as: Vasopressin Injection, USP (8-L arginine vasopressin), AVP, Pitressin®

Group 2: Vasopressin - Low Dose

Placebo Comparator DRUG

Participants in Group 3 will receive an equal volume of normal saline (placebo) infusion during their standard thrice-weekly dialysis treatments.

Also known as: Normal saline

Group 3: Placebo

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Columbia University: lead

Study Sites (1)

Columbia University Medical Center

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Hypertension; Kidney Failure, Chronic; Diabetes Insipidus

Interventions

Vasopressins; Arginine Vasopressin; Saline Solution

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pituitary Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Anjali Ganda, MD
• Organization: Columbia University Medical Center

ag355@columbia.edu

617-835-3789

Study Officials

• Anjali Ganda, M.D., M.S.

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2010
• First Posted: November 24, 2010
• Study Start: October 1, 2010
• Primary Completion: August 1, 2018
• Study Completion: August 1, 2018
• Last Updated: November 18, 2019
• Results First Posted: April 28, 2011

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)