Early Diuresis Following Colorectal Surgery

• Sponsor: Mayo Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT02351934
• Collaborator: (none)
• Enrollment: 123
• Location: 1
• Arms: 2
• Actual Duration (Months): 14
• Patients Per Site Per Month: 8.8

Study Details

Study Description

Brief Summary

The purpose of this study is to find out if giving a medicine called furosemide, which is a diuretic or water pill, after colon surgery will safely shorten the patient's length of hospital stay.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Disorders	Drug: Furosemide; Drug: Celecoxib; Drug: Gabapentin	Phase 4

Detailed Description

This study will assess if administration of a loop diuretic, specifically furosemide, to achieve euvolemia can safely reduce length of stay following colorectal surgery.

Study Design

• Study Type: Interventional
• Actual Enrollment: 123 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Prospective, Randomized Study Evaluating the Efficacy and Safety of Early Diuresis Following Colorectal Surgery
• Actual Study Start Date: Feb 1, 2015
• Actual Primary Completion Date: Apr 1, 2016
• Actual Study Completion Date: Apr 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Furosemide + Enhanced Recovery after Surgery (ERAS) Furosemide 10 mg IV on post-operative day #1 and/or 2, plus ERAS, as described in other arm.	Drug: Furosemide; Other Names: Lasix ; Drug: Celecoxib; Celecoxib is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain or inflammation.; Other Names: Celebrex ; Drug: Gabapentin; Gabapentin is a oral drug used to treat seizures, postherpetic neuralgia, and restless legs syndrome.; Other Names: Neurontin
Active Comparator: Enhanced Recovery after Surgery (ERAS) ERAS included administration of celecoxib and gabapentin in the pre-operative setting, single-injection intrathecal analgesic administration immediately prior to induction of general anesthesia, post-operative administration of scheduled acetaminophen and nonsteroidal anti-inflammatory drug (NSAID) or tramadol, and discontinuation of IV fluids by 0800 on postoperative day (POD) 1. Intraoperative fluid administration was dependent on the individual anesthesia provider with no unified commitment to either zero balance or goal-directed fluid therapy. Fluid status was determined based on patient weight. Patients were weighed preoperatively and daily post-operatively using either a bed scale or a unit-based scale.	Drug: Celecoxib; Celecoxib is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain or inflammation.; Other Names: Celebrex ; Drug: Gabapentin; Gabapentin is a oral drug used to treat seizures, postherpetic neuralgia, and restless legs syndrome.; Other Names: Neurontin

Outcome Measures

Primary Outcome Measures

1. Length of Hospital Stay [Up to 7 days]

   Participants will be followed for the duration of hospital stay, an expected average of 2-7 days.

Secondary Outcome Measures

1. Number of Participants Readmitted to Mayo Clinic Within 30-days [Within 30 days of release from hospital]

2. Number of Participants Requiring Nasogastric Tube Placement [Up to 7 days]

3. Time to Stool Output [Up to 4 days]

4. Number of Participants With Acute Kidney Injury [Up to 7 days]

   Acute kidney injury (AKI) refers to an abrupt decrease in kidney function, resulting in the retention of urea and other nitrogenous waste products and in the dysregulation of extracellular volume and electrolytes. The term AKI has largely replaced acute renal failure (ARF), reflecting the recognition that smaller decrements in kidney function that do not result in overt organ failure are of substantial clinical relevance and are associated with increased morbidity and mortality. The AKI experienced by these patients was not considered an adverse event.

5. Number of Participants With Hypokalemia [Up to 7 days]

   Hypokalemia is generally defined as a serum potassium level of less than 3.5 mmol/L.

Eligibility Criteria

Criteria

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

Inclusion Criteria

• All elective colorectal surgeries (CRS) utilizing the enhanced recovery pathway (ERP)

• The surgery involves resection

Exclusion Criteria

Exclusion Criteria for Randomization:

• Surgeries involving intraoperative radiation

• Ileostomy closures, when performed as the only surgical intervention

• Surgeries involving multiple disciplines (e.g., colorectal plus general surgery, colorectal plus gynecology surgery) except for colorectal surgeries plus ureteral stent placements.

• Chronic loop diuretic therapy (i.e., bumetanide, torsemide, furosemide, ethacrynic acid) including as needed administration of such therapy

• Patients receiving dialysis

• Creatinine clearance, calculated by the Cockcroft-Gault equation, less than 30 mL/min.

• Inpatient prior to surgery

• Allergy to furosemide

• Allergy to sulfa drugs if the allergy involves anaphylactic reaction

• Lack of serum creatinine concentration within 3 months preceding the surgery AND diagnosis of chronic kidney disease

Exclusion Criteria for Intervention (applies to both the intervention and control arm):

• Patient's weight on postoperative day (POD) #1 and POD #2 is less than preoperative weight.

• Blood pressure criteria: systolic blood pressure criteria less than 90 mmHg or greater than 30 mmHg below baseline on POD #1 and/or POD #2 immediately prior to administration of study drug.

• Complications within 48 hours of surgery

• Abscess (infected fluid collection, treated with CT drainage)

• Leak (defined by CT drainage or reoperation)

• Wound infection (treated with either antibiotics and/or open packing)

• Bowel obstruction (treated with reoperation)

• Reoperation

• Hemorrhage

• Weight change since admission on POD #1: > 5 kg

• Acute kidney injury on POD #1 and POD#2 defined as serum creatinine (SCr) increase ≥ 0.3 mg/dL or increase to ≥ 150% to 200% (1.5- to 2-fold) from baseline

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic in Rochester	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

• Mayo Clinic

Investigators

• Principal Investigator: Ilya Danelich, PharmD, RPh, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ilya M. Danelich, Pharm.D., R.Ph., PI, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT02351934
• Other Study ID Numbers: 14-008292; UL1TR000135
• First Posted: Jan 30, 2015
• Last Update Posted: May 7, 2018
• Last Verified: Apr 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Ilya M. Danelich, Pharm.D., R.Ph., PI, Mayo Clinic: colorectal surgery; volume status
• Additional relevant MeSH terms: Celecoxib; Furosemide; Gabapentin

Study Results

Participant Flow

Recruitment Details	Subjects were enrolled at Mayo Clinic in Rochester, Minnesota between February 2015 and April 2016.

Arm/Group Title	Furosemide + Enhanced Recovery After Surgery (ERAS)	Enhanced Recovery After Surgery (ERAS)
Arm/Group Description	Furosemide 10 mg IV on post-operative day #1 and/or 2, plus ERAS, as described in other arm.	ERAS included administration of celecoxib and gabapentin in the pre-operative setting, single-injection intrathecal analgesic administration immediately prior to induction of general anesthesia, post-operative administration of scheduled acetaminophen and nonsteroidal anti-inflammatory drug (NSAID) or tramadol, and discontinuation of IV fluids by 0800 on postoperative day (POD) 1. Intraoperative fluid administration was dependent on the individual anesthesia provider with no unified commitment to either zero balance or goal-directed fluid therapy. Fluid status was determined based on patient weight. Patients were weighed preoperatively and daily post-operatively using either a bed scale or a unit-based scale.
Period Title: Allocation
STARTED	62	61
Received Allocation	56	61
COMPLETED	56	61
NOT COMPLETED	6	0
Period Title: Allocation
STARTED	56	61
COMPLETED	44	51
NOT COMPLETED	12	10

Baseline Characteristics

Arm/Group Title	Furosemide + Enhanced Recovery After Surgery (ERAS)	Enhanced Recovery After Surgery (ERAS)	Total
Arm/Group Description	Furosemide 10 mg IV on post-operative day #1 and/or 2, plus ERAS, as described in other arm.	ERAS included administration of celecoxib and gabapentin in the pre-operative setting, single-injection intrathecal analgesic administration immediately prior to induction of general anesthesia, post-operative administration of scheduled acetaminophen and nonsteroidal anti-inflammatory drug (NSAID) or tramadol, and discontinuation of IV fluids by 0800 on postoperative day (POD) 1. Intraoperative fluid administration was dependent on the individual anesthesia provider with no unified commitment to either zero balance or goal-directed fluid therapy. Fluid status was determined based on patient weight. Patients were weighed preoperatively and daily post-operatively using either a bed scale or a unit-based scale.	Total of all reporting groups
Overall Participants	62	61	123
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	57	61	59
Sex: Female, Male (Count of Participants)
Female	22 35.5%	28 45.9%	50 40.7%
Male	40 64.5%	33 54.1%	73 59.3%
Region of Enrollment (Count of Participants)
United States	62 100%	61 100%	123 100%

Outcome Measures

1. Primary Outcome

Title	Length of Hospital Stay
Description	Participants will be followed for the duration of hospital stay, an expected average of 2-7 days.
Time Frame	Up to 7 days

Outcome Measure Data

Analysis Population Description

Intent to treat analysis

Arm/Group Title	Furosemide + Enhanced Recovery After Surgery (ERAS)	Enhanced Recovery After Surgery (ERAS)
Arm/Group Description	Furosemide 10 mg IV on post-operative day #1 and/or 2, plus ERAS, as described in other arm.	ERAS included administration of celecoxib and gabapentin in the pre-operative setting, single-injection intrathecal analgesic administration immediately prior to induction of general anesthesia, post-operative administration of scheduled acetaminophen and nonsteroidal anti-inflammatory drug (NSAID) or tramadol, and discontinuation of IV fluids by 0800 on postoperative day (POD) 1. Intraoperative fluid administration was dependent on the individual anesthesia provider with no unified commitment to either zero balance or goal-directed fluid therapy. Fluid status was determined based on patient weight. Patients were weighed preoperatively and daily post-operatively using either a bed scale or a unit-based scale.
Measure Participants	62	61
Median (Inter-Quartile Range) [hours]	99.6	80.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Furosemide + Enhanced Recovery After Surgery (ERAS), Enhanced Recovery After Surgery (ERAS)
	Comments	Significance level of 0.05 was used.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.564
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

2. Secondary Outcome

Title	Number of Participants Readmitted to Mayo Clinic Within 30-days
Time Frame	Within 30 days of release from hospital

Outcome Measure Data

Analysis Population Description

Intention to treat analysis

Arm/Group Title	Furosemide + Enhanced Recovery After Surgery (ERAS)	Enhanced Recovery After Surgery (ERAS)
Arm/Group Description	Furosemide 10 mg IV on post-operative day #1 and/or 2, plus ERAS, as described in other arm.	ERAS included administration of celecoxib and gabapentin in the pre-operative setting, single-injection intrathecal analgesic administration immediately prior to induction of general anesthesia, post-operative administration of scheduled acetaminophen and nonsteroidal anti-inflammatory drug (NSAID) or tramadol, and discontinuation of IV fluids by 0800 on postoperative day (POD) 1. Intraoperative fluid administration was dependent on the individual anesthesia provider with no unified commitment to either zero balance or goal-directed fluid therapy. Fluid status was determined based on patient weight. Patients were weighed preoperatively and daily post-operatively using either a bed scale or a unit-based scale.
Measure Participants	62	61
Count of Participants [Participants]	13 21%	10 16.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Furosemide + Enhanced Recovery After Surgery (ERAS), Enhanced Recovery After Surgery (ERAS)
	Comments	Significance level of 0.05 was used.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.675
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

3. Secondary Outcome

Title	Number of Participants Requiring Nasogastric Tube Placement
Time Frame	Up to 7 days

Outcome Measure Data

Analysis Population Description

Intention to Treat Analysis

Arm/Group Title	Furosemide + Enhanced Recovery After Surgery (ERAS)	Enhanced Recovery After Surgery (ERAS)
Arm/Group Description	Furosemide 10 mg IV on post-operative day #1 and/or 2, plus ERAS, as described in other arm.	ERAS included administration of celecoxib and gabapentin in the pre-operative setting, single-injection intrathecal analgesic administration immediately prior to induction of general anesthesia, post-operative administration of scheduled acetaminophen and nonsteroidal anti-inflammatory drug (NSAID) or tramadol, and discontinuation of IV fluids by 0800 on postoperative day (POD) 1. Intraoperative fluid administration was dependent on the individual anesthesia provider with no unified commitment to either zero balance or goal-directed fluid therapy. Fluid status was determined based on patient weight. Patients were weighed preoperatively and daily post-operatively using either a bed scale or a unit-based scale.
Measure Participants	62	61
Count of Participants [Participants]	6 9.7%	1 1.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Furosemide + Enhanced Recovery After Surgery (ERAS), Enhanced Recovery After Surgery (ERAS)
	Comments	Significance level of 0.05 was used.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.125
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

4. Secondary Outcome

Title	Time to Stool Output
Time Frame	Up to 4 days

Outcome Measure Data

Analysis Population Description

Intention to treat analysis

Arm/Group Title	Furosemide + Enhanced Recovery After Surgery (ERAS)	Enhanced Recovery After Surgery (ERAS)
Arm/Group Description	Furosemide 10 mg IV on post-operative day #1 and/or 2, plus ERAS, as described in other arm.	ERAS included administration of celecoxib and gabapentin in the pre-operative setting, single-injection intrathecal analgesic administration immediately prior to induction of general anesthesia, post-operative administration of scheduled acetaminophen and nonsteroidal anti-inflammatory drug (NSAID) or tramadol, and discontinuation of IV fluids by 0800 on postoperative day (POD) 1. Intraoperative fluid administration was dependent on the individual anesthesia provider with no unified commitment to either zero balance or goal-directed fluid therapy. Fluid status was determined based on patient weight. Patients were weighed preoperatively and daily post-operatively using either a bed scale or a unit-based scale.
Measure Participants	62	61
Median (Inter-Quartile Range) [hours]	48.8	45.4

5. Secondary Outcome

Title	Number of Participants With Acute Kidney Injury
Description	Acute kidney injury (AKI) refers to an abrupt decrease in kidney function, resulting in the retention of urea and other nitrogenous waste products and in the dysregulation of extracellular volume and electrolytes. The term AKI has largely replaced acute renal failure (ARF), reflecting the recognition that smaller decrements in kidney function that do not result in overt organ failure are of substantial clinical relevance and are associated with increased morbidity and mortality. The AKI experienced by these patients was not considered an adverse event.
Time Frame	Up to 7 days

Outcome Measure Data

Analysis Population Description

Intention to treat analysis

Arm/Group Title	Furosemide + Enhanced Recovery After Surgery (ERAS)	Enhanced Recovery After Surgery (ERAS)
Arm/Group Description	Furosemide 10 mg IV on post-operative day #1 and/or 2, plus ERAS, as described in other arm.	ERAS included administration of celecoxib and gabapentin in the pre-operative setting, single-injection intrathecal analgesic administration immediately prior to induction of general anesthesia, post-operative administration of scheduled acetaminophen and nonsteroidal anti-inflammatory drug (NSAID) or tramadol, and discontinuation of IV fluids by 0800 on postoperative day (POD) 1. Intraoperative fluid administration was dependent on the individual anesthesia provider with no unified commitment to either zero balance or goal-directed fluid therapy. Fluid status was determined based on patient weight. Patients were weighed preoperatively and daily post-operatively using either a bed scale or a unit-based scale.
Measure Participants	62	61
Count of Participants [Participants]	2 3.2%	2 3.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Furosemide + Enhanced Recovery After Surgery (ERAS), Enhanced Recovery After Surgery (ERAS)
	Comments	Significance level of 0.05 was used.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.595
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

6. Secondary Outcome

Title	Number of Participants With Hypokalemia
Description	Hypokalemia is generally defined as a serum potassium level of less than 3.5 mmol/L.
Time Frame	Up to 7 days

Outcome Measure Data

Analysis Population Description

Intention to treat analysis

Arm/Group Title	Furosemide + Enhanced Recovery After Surgery (ERAS)	Enhanced Recovery After Surgery (ERAS)
Arm/Group Description	Furosemide 10 mg IV on post-operative day #1 and/or 2, plus ERAS, as described in other arm.	ERAS included administration of celecoxib and gabapentin in the pre-operative setting, single-injection intrathecal analgesic administration immediately prior to induction of general anesthesia, post-operative administration of scheduled acetaminophen and nonsteroidal anti-inflammatory drug (NSAID) or tramadol, and discontinuation of IV fluids by 0800 on postoperative day (POD) 1. Intraoperative fluid administration was dependent on the individual anesthesia provider with no unified commitment to either zero balance or goal-directed fluid therapy. Fluid status was determined based on patient weight. Patients were weighed preoperatively and daily post-operatively using either a bed scale or a unit-based scale.
Measure Participants	62	61
Count of Participants [Participants]	2 3.2%	3 4.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Furosemide + Enhanced Recovery After Surgery (ERAS), Enhanced Recovery After Surgery (ERAS)
	Comments	Significance level of 0.05 was used.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.985
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Adverse Events

Time Frame	1 month
Arm/Group Title	Furosemide + Enhanced Recovery After Surgery (ERAS)		Enhanced Recovery After Surgery (ERAS)
Arm/Group Description	Furosemide 10 mg IV on post-operative day #1 and/or 2, plus ERAS, as described in other arm.		ERAS included administration of celecoxib and gabapentin in the pre-operative setting, single-injection intrathecal analgesic administration immediately prior to induction of general anesthesia, post-operative administration of scheduled acetaminophen and nonsteroidal anti-inflammatory drug (NSAID) or tramadol, and discontinuation of IV fluids by 0800 on postoperative day (POD) 1. Intraoperative fluid administration was dependent on the individual anesthesia provider with no unified commitment to either zero balance or goal-directed fluid therapy. Fluid status was determined based on patient weight. Patients were weighed preoperatively and daily post-operatively using either a bed scale or a unit-based scale.
All Cause Mortality
	Furosemide + Enhanced Recovery After Surgery (ERAS)		Enhanced Recovery After Surgery (ERAS)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/62 (0%)		0/61 (0%)
Serious Adverse Events
	Furosemide + Enhanced Recovery After Surgery (ERAS)		Enhanced Recovery After Surgery (ERAS)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/62 (0%)		0/61 (0%)
Other (Not Including Serious) Adverse Events
	Furosemide + Enhanced Recovery After Surgery (ERAS)		Enhanced Recovery After Surgery (ERAS)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/62 (12.9%)		3/61 (4.9%)
Blood and lymphatic system disorders
Decreased Potassium	2/62 (3.2%)	2	3/61 (4.9%)	3
Hematoma/Anemia	1/62 (1.6%)	1	0/61 (0%)	0
Cardiac disorders
Decreased blood pressure	3/62 (4.8%)	3	0/61 (0%)	0
Atrial Fibrillation	1/62 (1.6%)	1	0/61 (0%)	0
Increased heart rate	1/62 (1.6%)	1	0/61 (0%)	0
General disorders
Increased temperature	1/62 (1.6%)	1	0/61 (0%)	0
Renal and urinary disorders
Increased Serum Creatinine	2/62 (3.2%)	2	0/61 (0%)	0
Urine leak	0/62 (0%)	0	1/61 (1.6%)	1

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.