Stop Hypernatremia, Use Metolazone, for Aggressive, Controlled, Effective Diuresis (SHUM)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2012 by Oregon Health and Science University.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
David Steiger, JD MD, Oregon Health and Science University
ClinicalTrials.gov Identifier:
NCT01617798
First received: June 1, 2012
Last updated: June 26, 2012
Last verified: June 2012
  Purpose

Patients who are on mechanical ventilation in an intensive care unit often require diursis as part of their pre-extubation regimen. The drug of choice for diuresis has traditionally been furosemide. However, this drug cause hypernatremia (a rise in serum sodium) in a significant proportion of patients. Hypernatremia is traditionally treated by providing free water supplementation to the patient. This strategy creates a vicious and unproductive cycle of giving free water, and then diuresing it off. We propose a strategy for breaking this cycle by using a second diuretic-- metolazone-- which has a tendency to rid the body of more sodium, thereby minimizing hypernatremia.


Condition Intervention
Respiratory Failure
Volume Overload
Hypernatremia
Drug: Supplemental metolazone diuresis
Drug: Placebo Comparator: Control-- furosemide (lasix) only

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Stop Hypernatremia, Use Metolazone for Aggressive, Controlled, Effective Diuresis

Resource links provided by NLM:


Further study details as provided by Oregon Health and Science University:

Primary Outcome Measures:
  • Fluid balance [ Time Frame: 24, 36, 48, and 72 hours after either protocol is initiated ] [ Designated as safety issue: No ]
    Differences in fluid balance (total net liters negative from the time diuresis is initiated) between the study group and control group at the following intervals: 24, 36, 48, and 72 hours after either protocol is initiated.


Secondary Outcome Measures:
  • Serum sodium [ Time Frame: Continuous for 72 hours ] [ Designated as safety issue: Yes ]
    Number patients whose Na remains below 145 (meq/L) during the period of diuresis; versus the number of patients whose sodium exceeds 145 (meq/L) and require free water replacement.

  • Hyponatremia [ Time Frame: Continuous for up to 72 hours ] [ Designated as safety issue: Yes ]
    Number of patients who develop hyponatremia (Na < 136 meq/L)

  • Time to extubation [ Time Frame: Unitl the patient is actually extubated, undergoes tracheostomy, or expires. ] [ Designated as safety issue: No ]
    Time in hours from initiation of protocol to extubation (difference between study group and control group

  • Acute Kidney Injury [ Time Frame: Continuous for the first 72 hours ] [ Designated as safety issue: Yes ]
    Number of patients who develop acute kidney injury (increase in creatinine by more than 25%)


Estimated Enrollment: 54
Study Start Date: June 2012
Estimated Study Completion Date: June 2013
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Control-- furosemide (lasix) only

Control arm receives standard of care diuresis with furosemide(lasix)only. The treatment team will decide the dosing of furosemide (lasix).

No actual placebo is administered.

Drug: Placebo Comparator: Control-- furosemide (lasix) only
Control arm will receive furosemide as monotherapy for diuresis
Other Name: furosemide, lasix, metolazone
Active Comparator: Study Arm
Study arm receives evolving standard of care diuresis with furosemide and metolazone.
Drug: Supplemental metolazone diuresis
Patients in the Study Arm will receive supplemental diuresis with metolazone 2.5 mg per dobhoff tube twice daily, in addition to furosemide as the primary team sees fit.
Other Name: furosemide, lasix

Detailed Description:

Mechanical ventilation is a mainstay of Intensive Care. Weaning from mechanical ventilation remains a significant issue in Intensive Care Unit (ICU) care worldwide. It is well established that a strategy of diuresis with negative fluid balance shortens the duration of mechanical ventilation in both acute lung injury and cardiogenic pulmonary edema patients. Despite publication of at least one formalized but complex evidence-based conservative fluid strategy, there is no practical, uniformly implemented protocol for setting or achieving volume status targets. The default approach at many hospitals involves using ad hoc doses (either intermittent or continuous) of a loop diuretic (usually furosemide) with instructions to monitor fluid balance and follow electrolytes in an attempt to reach arbitrary target volume diuresis. Moreover, there are barriers to achieving any particular target, including pre-existing renal failure/diuretic resistance, diuretic-induced creatinine elevation, acquired diuretic resistance, hypotension from volume loss, and electrolyte derangements including hypokalemia and hypernatremia. Strategies exist for preventing or treating the above complications but there is presently no accepted standard for preventing or treating diuretic-induced hypernatremia. In fact, the standard current intervention is to replace the free water deficit that may be induced by the loop diuretic, while simultaneously perpetuating the free water deficit by continuing to administer the causative loop diuretic. This approach is circular and does not effectuate the desired negative fluid balance. We will address the lack of an accepted prevention strategy using a randomized controlled clinical trial in ICU patients with the following specific aims:

  1. Conduct a randomized, pilot trial of standard versus metolazone supplemented diuresis in ICU patients with the primary outcome of improved negative fluid balance.
  2. Assess secondary outcomes including time to extubation, exacerbation of renal failure, and incidence of electrolyte derrangements in the treatment and control arms.
  3. Track whether initial hypernatremia within the control group is a risk factor for poor diuresis with furosemide, and whether it delays extubation.

The anticipated benefits of our proposed intervention involve fundamental ICU and patient care quality measures: avoiding the pitfalls of hypernatremia and diuretic resistance should lead to more effective diuresis, which should in turn lead to a more negative fluid balance, earlier liberation from the ventilator, and a shorter length of stay in the ICU.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • ICU patients who are intubated and slated for diuresis in anticipation of extubation.
  • Patients must be hypernatremic (Na > 140 mEq/L) at the time diuresis is initiated or become hypernatremic over the course of receiving loop diuretics in anticipation of extubation.
  • GFR > 30 ml/min [as calculated by the MedCalc MDRD formula {GFR = 170 x PCr - 0.999 x Age - 0.176 x BUN - 0.170 x Albumin0.318 x 0.762 (for women) x 1.180 (for blacks)} ]

Exclusion Criteria:

  • History of allergy to furosemide or any thiazide diuretic
  • Inability to place enteral access
  • Moribund status
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01617798

Contacts
Contact: James Case, MD 5034949000 Caseja@ohsu.edu

Locations
United States, Oregon
Oregon Health Sciences University Recruiting
Portland, Oregon, United States, 97239
Contact: Dan Hagg, MD         
Principal Investigator: David Steiger, JD, MD         
Principal Investigator: Dan Hagg, MS, MD         
Sponsors and Collaborators
Oregon Health and Science University
Investigators
Principal Investigator: David Steiger, JD MD Oregon Health and Science University
Principal Investigator: Dan Hagg, MS MD Oregon Health and Science University
  More Information

No publications provided

Responsible Party: David Steiger, JD MD, Critical Care Fellow, Oregon Health and Science University
ClinicalTrials.gov Identifier: NCT01617798     History of Changes
Other Study ID Numbers: IRB00007857
Study First Received: June 1, 2012
Last Updated: June 26, 2012
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Hypernatremia
Respiratory Insufficiency
Metabolic Diseases
Respiration Disorders
Respiratory Tract Diseases
Water-Electrolyte Imbalance
Furosemide
Metolazone
Antihypertensive Agents
Cardiovascular Agents
Diuretics
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Natriuretic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sodium Chloride Symporter Inhibitors
Sodium Potassium Chloride Symporter Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014