Early Diuresis Following Colorectal Surgery

• ClinicalTrials.gov Identifier: NCT02351934
• Recruitment Status: Completed
• First Posted: January 30, 2015
• Results First Posted: June 27, 2017
• Last Update Posted: May 7, 2018
• Sponsor: Mayo Clinic
• Information provided by (Responsible Party): Ilya M. Danelich, Pharm.D., R.Ph., Mayo Clinic

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 (Clinical Trial)
• 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: February 2015
• Actual Primary Completion Date: April 2016
• Actual Study Completion Date: April 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 Name: Lasix; Drug: Celecoxib; Celecoxib is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain or inflammation.; Other Name: Celebrex; Drug: Gabapentin; Gabapentin is a oral drug used to treat seizures, postherpetic neuralgia, and restless legs syndrome.; Other Name: 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 Name: Celebrex; Drug: Gabapentin; Gabapentin is a oral drug used to treat seizures, postherpetic neuralgia, and restless legs syndrome.; Other Name: Neurontin

Outcome Measures

Primary Outcome Measures :

1. Length of Hospital Stay [ Time Frame: 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 [ Time Frame: Within 30 days of release from hospital ]
2. Number of Participants Requiring Nasogastric Tube Placement [ Time Frame: Up to 7 days ]
3. Time to Stool Output [ Time Frame: Up to 4 days ]
4. Number of Participants With Acute Kidney Injury [ Time Frame: 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 [ Time Frame: Up to 7 days ]
   Hypokalemia is generally defined as a serum potassium level of less than 3.5 mmol/L.

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

• 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

United States, Minnesota

Mayo Clinic in Rochester

Rochester, Minnesota, United States, 55905

Sponsors and Collaborators

Mayo Clinic

Investigators

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

More Information

• Responsible Party: Ilya M. Danelich, Pharm.D., R.Ph., PI, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT02351934
• Other Study ID Numbers: 14-008292; UL1TR000135 ( U.S. NIH Grant/Contract )
• First Posted: January 30, 2015
• Results First Posted: June 27, 2017
• Last Update Posted: May 7, 2018
• Last Verified: April 2018

Individual Participant Data (IPD) Sharing Statement:

• 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., Mayo Clinic:

colorectal surgery; volume status

Additional relevant MeSH terms:

Celecoxib; Furosemide; Gabapentin; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anticonvulsants; Anti-Anxiety Agents; Tranquilizing Agents; Central Nervous System Depressants; Psychotropic Drugs; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Neurotransmitter Agents; Antimanic Agents; Diuretics; Natriuretic Agents; Sodium Potassium Chloride Symporter Inhibitors; Membrane Transport Modulators