Mannitol - Potential Role in Hemodialysis Initiation for Reduction of Intra-dialytic Hypotension

• Sponsor: Brigham and Women's Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT01520207
• Collaborator: (none)
• Enrollment: 52
• Location: 1
• Arms: 2
• Actual Duration (Months): 79
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

Kidney failure can result from a variety of conditions and can be temporary or permanent. Hemodialysis is available as a replacement treatment to perform the work that the kidneys normally do. However, the dialysis procedure can be associated with rapid changes in the composition of the blood - this may lead to changes in blood pressure and in turn reduced blood supply to important parts of the body. We aim to investigate if giving a medicine (called mannitol) during dialysis may be able to reduce the frequency of these low blood pressure events.

Condition or Disease	Intervention/Treatment	Phase
Intra-dialytic Hypotension	Drug: Mannitol (20%); Drug: 0.9% saline	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 52 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Other
• Official Title: Pilot Study of Intravenous Mannitol During Hemodialysis Initiation to Reduce the Occurrence of Intra-dialytic Hypotension.
• Actual Study Start Date: May 1, 2012
• Actual Primary Completion Date: Jul 1, 2016
• Actual Study Completion Date: Dec 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo group: (0.9% normal saline) 0.9% saline will be administered (IV) during the hemodialysis session at 1.25mL/kg/hour (max 375mLs per session). Administration will be discontinued 30 minutes before the end of the hemodialysis session.	Drug: 0.9% saline; 1.25mL/kg/hour; maximum 125mLs/hour; maximum total volume 375mLs per treatment
Active Comparator: Intervention: intravenous mannitol (20%) Mannitol will be administered (IV) during the hemodialysis session at a maximum rate of 0.25g/kg/hour (maximum rate 25g/hour; maximum 75g per session; maximum volume 375mLs per session). Administration will be discontinued 30 minutes before the end of the hemodialysis session.	Drug: Mannitol (20%); 0.25g/kg/hour (maximum rate 25g/hour; maximum 75g per session; maximum volume 375mLs per session)

Outcome Measures

Primary Outcome Measures

1. Efficacy of Mannitol Administration in Reducing the Frequency of Intra-dialytic Hypotension (Decline in Systolic Blood Pressure) During the First Three Hemodialysis Initiation Sessions. [First three hemodialysis sessions (5 days)]

   SBP decline during first three sessions

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Renal failure requiring intermittent hemodialysis initiation; adult patients aged over 18 years; written informed consent

Exclusion Criteria:

• Hyponatremia <130 mmol/L; acute myocardial infarction or stroke in previous 7 days; cardiac transplant; ventricular arrhythmia; unstable angina; use of pressors/midodrine; enrollment in conflicting research study; institutionalized individuals; pregnancy; prisoners; documented allergy to mannitol

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115

Sponsors and Collaborators

• Brigham and Women's Hospital

Investigators

• Principal Investigator: Sushrut S Waikar, MD, MPH, Brigham and Women's Hospital, Harvard Medical School
• Principal Investigator: Finnian R Mc Causland, MB, MMSc, Brigham and Women's Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sushrut S Waikar, Associate Professor of Medicine, Harvard Medical School, Brigham and Women's Hospital
• ClinicalTrials.gov Identifier: NCT01520207
• Other Study ID Numbers: NCT01520207
• First Posted: Jan 27, 2012
• Last Update Posted: Jan 30, 2019
• Last Verified: Jan 1, 2019

• Additional relevant MeSH terms: Hypotension; Mannitol

Study Results

Participant Flow

Recruitment Details	July 2012 - Jul 2016

Arm/Group Title	Placebo Group: (0.9% Normal Saline)	Intervention: Intravenous Mannitol (20%)
Arm/Group Description	0.9% saline will be administered (IV) during the hemodialysis session at 1.25mL/kg/hour (max 375mLs per session). Administration will be discontinued 30 minutes before the end of the hemodialysis session. 0.9% saline: 1.25mL/kg/hour; maximum 125mLs/hour; maximum total volume 375mLs per treatment	Mannitol will be administered (IV) during the hemodialysis session at a maximum rate of 0.25g/kg/hour (maximum rate 25g/hour; maximum 75g per session; maximum volume 375mLs per session). Administration will be discontinued 30 minutes before the end of the hemodialysis session. Mannitol (20%): 0.25g/kg/hour (maximum rate 25g/hour; maximum 75g per session; maximum volume 375mLs per session)
Period Title: Overall Study
STARTED	27	25
COMPLETED	25	25
NOT COMPLETED	2	0

Baseline Characteristics

Arm/Group Title	Placebo Group: (0.9% Normal Saline)	Intervention: Intravenous Mannitol (20%)	Total
Arm/Group Description	0.9% saline will be administered (IV) during the hemodialysis session at 1.25mL/kg/hour (max 375mLs per session). Administration will be discontinued 30 minutes before the end of the hemodialysis session. 0.9% saline: 1.25mL/kg/hour; maximum 125mLs/hour; maximum total volume 375mLs per treatment	Mannitol will be administered (IV) during the hemodialysis session at a maximum rate of 0.25g/kg/hour (maximum rate 25g/hour; maximum 75g per session; maximum volume 375mLs per session). Administration will be discontinued 30 minutes before the end of the hemodialysis session. Mannitol (20%): 0.25g/kg/hour (maximum rate 25g/hour; maximum 75g per session; maximum volume 375mLs per session)	Total of all reporting groups
Overall Participants	27	25	52
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.7 (14.7)	53.4 (17.4)	55.6 (16)
Sex: Female, Male (Count of Participants)
Female	13 48.1%	13 52%	26 50%
Male	14 51.9%	12 48%	26 50%
Region of Enrollment (participants) [Number]
United States	27 100%	25 100%	52 100%

Outcome Measures

1. Primary Outcome

Title	Efficacy of Mannitol Administration in Reducing the Frequency of Intra-dialytic Hypotension (Decline in Systolic Blood Pressure) During the First Three Hemodialysis Initiation Sessions.
Description	SBP decline during first three sessions
Time Frame	First three hemodialysis sessions (5 days)

Outcome Measure Data

Analysis Population Description

SBP decline

Arm/Group Title	Placebo Group: (0.9% Normal Saline)	Intervention: Intravenous Mannitol (20%)
Arm/Group Description	0.9% saline will be administered (IV) during the hemodialysis session at 1.25mL/kg/hour (max 375mLs per session). Administration will be discontinued 30 minutes before the end of the hemodialysis session. 0.9% saline: 1.25mL/kg/hour; maximum 125mLs/hour; maximum total volume 375mLs per treatment	Mannitol will be administered (IV) during the hemodialysis session at a maximum rate of 0.25g/kg/hour (maximum rate 25g/hour; maximum 75g per session; maximum volume 375mLs per session). Administration will be discontinued 30 minutes before the end of the hemodialysis session. Mannitol (20%): 0.25g/kg/hour (maximum rate 25g/hour; maximum 75g per session; maximum volume 375mLs per session)
Measure Participants	27	25
Mean (Standard Deviation) [mmHg]	19 (16)	15 (11)

Adverse Events

Time Frame	4 years
Adverse Event Reporting Description	Adverse events were monitored for all participants during their HD sessions
Arm/Group Title	Placebo Group: (0.9% Normal Saline)		Intervention: Intravenous Mannitol (20%)
Arm/Group Description	0.9% saline will be administered (IV) during the hemodialysis session at 1.25mL/kg/hour (max 375mLs per session). Administration will be discontinued 30 minutes before the end of the hemodialysis session. 0.9% saline: 1.25mL/kg/hour; maximum 125mLs/hour; maximum total volume 375mLs per treatment		Mannitol will be administered (IV) during the hemodialysis session at a maximum rate of 0.25g/kg/hour (maximum rate 25g/hour; maximum 75g per session; maximum volume 375mLs per session). Administration will be discontinued 30 minutes before the end of the hemodialysis session. Mannitol (20%): 0.25g/kg/hour (maximum rate 25g/hour; maximum 75g per session; maximum volume 375mLs per session)
All Cause Mortality
	Placebo Group: (0.9% Normal Saline)		Intervention: Intravenous Mannitol (20%)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/27 (0%)		0/25 (0%)
Serious Adverse Events
	Placebo Group: (0.9% Normal Saline)		Intervention: Intravenous Mannitol (20%)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/27 (0%)		0/25 (0%)
Other (Not Including Serious) Adverse Events
	Placebo Group: (0.9% Normal Saline)		Intervention: Intravenous Mannitol (20%)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/27 (66.7%)		17/25 (68%)
Cardiac disorders
Hypertension	10/27 (37%)	15	9/25 (36%)	15
Hypotension	2/27 (7.4%)	4	2/25 (8%)	2
Chest Pain	0/27 (0%)	0	2/25 (8%)	2
Tachycardia	0/27 (0%)	0	1/25 (4%)	1
Gastrointestinal disorders
Nausea	5/27 (18.5%)	5	1/25 (4%)	1
Infections and infestations
UTI	0/27 (0%)	0	1/25 (4%)	1
Musculoskeletal and connective tissue disorders
Cramps	2/27 (7.4%)	2	1/25 (4%)	2
Nervous system disorders
Headache	2/27 (7.4%)	3	1/25 (4%)	1
Confusion	2/27 (7.4%)	2	1/25 (4%)	1
Respiratory, thoracic and mediastinal disorders
Oxygen Requirement	2/27 (7.4%)	2	4/25 (16%)	7
Vascular disorders
Access issues	2/27 (7.4%)	2	2/25 (8%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.