Peritoneal Dialysis vs Furosemide for Acute Kidney Injury After Cardiopulmonary Bypass

• Sponsor: Children's Hospital Medical Center, Cincinnati (Other)
• Overall Status: Completed
• CT.gov ID: NCT01709227
• Collaborator: (none)
• Enrollment: 73
• Location: 1
• Arms: 2
• Duration (Months): 44
• Patients Per Site Per Month: 1.7

Study Details

Study Description

Brief Summary

Acute kidney injury (AKI) after cardiopulmonary bypass (CPB) in infants is common and associated with poor outcomes. Peritoneal dialysis (PD) and furosemide have been used to attain negative fluid balance due to AKI induced oliguria, but have not been compared prospectively. The investigators will prospectively compare outcomes of infants with oliguria after CPB randomized to PD vs. furosemide with the hypothesis that infants receiving PD have superior outcomes.

Condition or Disease	Intervention/Treatment	Phase
Acute Kidney Injury	Drug: Furosemide; Procedure: Peritoneal Dialysis	N/A

Detailed Description

Background: Acute kidney injury (AKI) is a common postoperative complication after heart surgery with cardiopulmonary bypass (CPB). Multiple studies have demonstrated that patients with AKI have worse clinical outcomes, such as longer ventilation times and increased length of stay, which is thought to be secondary to associated oliguria and subsequent fluid overload. Studies suggest that early renal replacement therapy (RRT) via peritoneal dialysis (PD) may prevent fluid overload and therefore be a superior management to diuretic (i.e. furosemide) administration. However, there is no published evidence to suggest superiority or laboratory data available to guide decision making.

Objective: Our primary objective is to determine if early institution of PD improves clinical outcomes compared to administration of furosemide in post-operative cardiac infants with acute kidney injury. We hypothesize that early initiation of PD will improve clinical outcomes. We will determine if these clinical outcomes will be better among good responders of furosemide compared to poor responders. We will determine if postoperative NGAL concentrations are predictive of poor response to furosemide.

Design / Methods: The study will be a single-center randomized clinical trial among neonates undergoing cardiac surgery with CPB with planned placement of a PD catheter due to risk of AKI. If patients demonstrate oliguria within the first postoperative day, they will be randomized to early PD or trial of furosemide. Clinical and laboratory data will be collected and compared between groups.

Study Design

• Study Type: Interventional
• Actual Enrollment: 73 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Early Renal Replacement Therapy vs. Furosemide for Neonates With Oliguria After Cardiopulmonary Bypass
• Study Start Date: Oct 1, 2011
• Actual Primary Completion Date: Jun 1, 2015
• Actual Study Completion Date: Jun 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Furosemide Patients randomized to the furosemide arm will be given 1 mg/kg intravenously every 6 hours for 2 doses and then as directed by CICU attending to augment urine output. Patients within this arm who have urine output <1 ml/kg/hr over 16 hours after the first dose of Lasix will be considered poor responders. These patients may be started on PD if clinically indicated. Those who show good response (urine output >1 ml/kg/hr over subsequent 16 hours) will continue furosemide as needed to augment urine output. If they subsequently develop oliguria or fluid overload unresponsive to diuretic therapy, these patients may later be started on PD at discretion of CICU attending with consultation of nephrology service.	Drug: Furosemide; Patients randomized to the furosemide arm will be given 1 mg/kg intravenously every 6 hours for 2 doses and then as directed by CICU attending to augment urine output. Patients within this arm who have urine output <1 ml/kg/hr over 16 hours after the first dose of Lasix will be considered poor responders. These patients may be started on PD if clinically indicated. Those who show good response (urine output >1 ml/kg/hr over subsequent 16 hours) will continue furosemide as needed to augment urine output. If they subsequently develop oliguria or fluid overload unresponsive to diuretic therapy, these patients may later be started on PD at discretion of CICU attending with consultation of nephrology service.; Other Names: Lasix
Experimental: Peritoneal dialysis Patients within the PD arm will begin PD with a standardized dialysis plan of 10ml/kg of 1.5% Dianeal™ with 1 hours cycles (5 minute fill, 45 minute dwell and 10 minute drain). Further PD management will be directed by CICU attending and Nephrology service	Procedure: Peritoneal Dialysis; Patients within the PD arm will begin PD with a standardized dialysis plan of 10ml/kg of 1.5% Dianeal™ with 1 hours cycles (5 minute fill, 45 minute dwell and 10 minute drain). Further PD management and discontinuation will be directed by CICU attending and Nephrology service.; Other Names: PD

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Negative Fluid Balance on Postop Day 1 [Postop day 1]

   Difference of inputs and outputs, including urine output and PD drainage.

Secondary Outcome Measures

1. Respiratory Support Administered [Duration of postoperative intubation (average time approximately- 1 week)]

   Duration of initial course of postoperative mechanical ventilation

2. NGAL Concentration [Pre-op, and postop (2hr, 6hr, 12hr, 24hr, 48hr)]

3. Duration of Cardiac ICU Stay [Average 2 weeks]

   Total days of initial postoperative stay in cardiac ICU

4. Duration of Hospital Stay [Average 4 weeks]

   Total days of initial postoperative stay in hospital

5. All Cause Mortality [duration of hospitalization (an average of 2 weeks)]

   In-hospital mortality

6. Renal/Electrolyte Abnormalities [Postop morning 1-5]

   Total sum of renal and electrolyte abnormalities over the first 5 postoperative days as defined in the protocol

7. Doses of Potassium Chloride or Arginine Chloride Required [Postop day 0-5]

   Total doses of potassium chloride or arginine chloride given during the first five postoperative days.

8. B-Natriuretic Peptide [At 24hours and 48 hours postoperative]

   BNP measured at 24 and 48 hours postoperatively

9. Modified Oxygenation Index [at 24 and 48 hours postoperative]

   Product of Mean airway pressure delivered by mechanical ventilation and FiO2 of administered oxygen

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 6 Months
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age less than 6 months of age;

• Undergoing cardiothoracic surgery with CPB;

• Planned placement of PD catheter per institutional standard of care criteria.

Exclusion Criteria:

• Pre-existing chronic kidney disease stage 3 or above (correlating with estimated GFR<60 ml/min/m2, which will be calculated using routine preoperative serum creatinine value using the modified Schwartz equation).

• Known history of allergy to furosemide.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cincinnati Childrens Hospital Medical Center	Cincinnati	Ohio	United States	45223

Sponsors and Collaborators

• Children's Hospital Medical Center, Cincinnati

Investigators

• Principal Investigator: David M Kwiatkowski, MD, Cinncinnati Children's Hospital Medical Center
• Study Director: Catherine D Krawczeski, MD, Cinncinnati Children's Hospital Medical Center
• Study Director: Stuart L Goldstein, MD, Cinncinnati Children's Hospital Medical Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Center for Acute Care Nephology at Cincinnati Childrens

Publications

None provided.

• Responsible Party: Children's Hospital Medical Center, Cincinnati
• ClinicalTrials.gov Identifier: NCT01709227
• Other Study ID Numbers: 2011-1730
• First Posted: Oct 18, 2012
• Last Update Posted: Jun 9, 2017
• Last Verified: May 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Children's Hospital Medical Center, Cincinnati: Acute kidney injury; AKI; cardiopulmonary bypass
• Additional relevant MeSH terms: Acute Kidney Injury; Furosemide

Study Results

Participant Flow

Arm/Group Title	Furosemide	Peritoneal Dialysis
Arm/Group Description	Patients randomized to the furosemide arm will be given 1 mg/kg intravenously every 6 hours for 2 doses and then as directed by CICU attending to augment urine output. Patients within this arm who have urine output <1 ml/kg/hr over 16 hours after the first dose of Lasix will be considered poor responders. These patients may be started on PD if clinically indicated. Those who show good response (urine output >1 ml/kg/hr over subsequent 16 hours) will continue furosemide as needed to augment urine output. If they subsequently develop oliguria or fluid overload unresponsive to diuretic therapy, these patients may later be started on PD at discretion of CICU attending with consultation of nephrology service. Furosemide: Patients randomized to the furosemide arm are given 1 mg/kg intravenously every 6 hours for 2 doses and then as directed by CICU attending to augment urine output. Patients within this arm who have urine output <1 ml/kg/hr over 16 hours after the first dose of Lasix	Patients within the PD arm will begin PD with a standardized dialysis plan of 10ml/kg of 1.5% Dianeal™ with 1 hours cycles (5 minute fill, 45 minute dwell and 10 minute drain). Further PD management will be directed by CICU attending and Nephrology service Peritoneal Dialysis: Patients within the PD arm will begin PD with a standardized dialysis plan of 10ml/kg of 1.5% Dianeal™ with 1 hours cycles (5 minute fill, 45 minute dwell and 10 minute drain). Further PD management and discontinuation will be directed by CICU attending and Nephrology service. One potential outcome during use of a peritoneal dialysis catheter is the development of a Pleural Peritoneal communication. In this event, dialysis fluid is instilled in the peritoneum and then leaks into the pleural space through a defect in the diaphragm. This fluid is then drained out of a surgical chest tube. This impairs the ability to perform peritoneal dialysis and thus is a reason to not complete the randomized arm.
Period Title: Overall Study
STARTED	32	41
COMPLETED	31	32
NOT COMPLETED	1	9

Baseline Characteristics

Arm/Group Title	Furosemide	Peritoneal Dialysis	Total
Arm/Group Description	Patients randomized to receive furosemide	Patients randomized to receive peritoneal dialysis	Total of all reporting groups
Overall Participants	32	41	73
Age (days) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [days]	9	8	8
Sex: Female, Male (Count of Participants)
Female	11 34.4%	15 36.6%	26 35.6%
Male	21 65.6%	26 63.4%	47 64.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 3.1%	1 2.4%	2 2.7%
Not Hispanic or Latino	31 96.9%	40 97.6%	71 97.3%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 3.1%	0 0%	1 1.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 6.3%	2 4.9%	4 5.5%
White	29 90.6%	37 90.2%	66 90.4%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	2 4.9%	2 2.7%
Region of Enrollment (participants) [Number]
United States	32 100%	41 100%	73 100%
Weight (kg) (kg) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [kg]	3.4	3.4	3.4
Length (cm) (cm) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [cm]	50	50	50
Baseline Creatinine (mg/dL) (mg/dl) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [mg/dl]	0.4	0.4	0.4

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Negative Fluid Balance on Postop Day 1
Description	Difference of inputs and outputs, including urine output and PD drainage.
Time Frame	Postop day 1

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Furosemide	Peritoneal Dialysis
Arm/Group Description	Patients randomized to furosemide	Patients randomized to peritoneal dialysis
Measure Participants	32	41
Count of Participants [Participants]	21 65.6%	29 70.7%

2. Secondary Outcome

Title	Respiratory Support Administered
Description	Duration of initial course of postoperative mechanical ventilation
Time Frame	Duration of postoperative intubation (average time approximately- 1 week)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Furosemide	Peritoneal Dialysis
Arm/Group Description	Patients randomized to furosemide	Patients randomized to peritoneal dialysis
Measure Participants	32	41
Median (Inter-Quartile Range) [days]	4	3

3. Secondary Outcome

Title	NGAL Concentration
Time Frame	Pre-op, and postop (2hr, 6hr, 12hr, 24hr, 48hr)

Outcome Measure Data

Analysis Population Description

Data were collected but not analyzed. Due to a high incidence of volatile and un-reportable NGAL levels, concerns were raised about the storage or processing of samples affecting data validity. Given the overwhelming concern of erroneous data, analysis was not performed as planned.

Arm/Group Title	Furosemide	Peritoneal Dialysis
Arm/Group Description	Patients randomized to furosemide	Patients randomized to PD
Measure Participants	0	0

4. Secondary Outcome

Title	Duration of Cardiac ICU Stay
Description	Total days of initial postoperative stay in cardiac ICU
Time Frame	Average 2 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Furosemide	Peritoneal Dialysis
Arm/Group Description	Patients randomized to furosemide	Patients randomized to peritoneal dialysis
Measure Participants	32	41
Median (Inter-Quartile Range) [days]	9	7

5. Secondary Outcome

Title	Duration of Hospital Stay
Description	Total days of initial postoperative stay in hospital
Time Frame	Average 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Furosemide	Peritoneal Dialysis
Arm/Group Description	Patients randomized to furosemide	Patients randomized to peritoneal dialysis
Measure Participants	32	41
Median (Inter-Quartile Range) [days]	15	14

6. Secondary Outcome

Title	All Cause Mortality
Description	In-hospital mortality
Time Frame	duration of hospitalization (an average of 2 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Furosemide	Peritoneal Dialysis
Arm/Group Description	Patients randomized to furosemide	Patients randomized to peritoneal dialysis
Measure Participants	32	41
Count of Participants [Participants]	3 9.4%	1 2.4%

7. Secondary Outcome

Title	Renal/Electrolyte Abnormalities
Description	Total sum of renal and electrolyte abnormalities over the first 5 postoperative days as defined in the protocol
Time Frame	Postop morning 1-5

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Furosemide	Peritoneal Dialysis
Arm/Group Description	Patients randomized to furosemide	Patients randomized to peritoneal dialysis
Measure Participants	32	41
Median (Inter-Quartile Range) [abnormalities]	6	4

8. Secondary Outcome

Title	Doses of Potassium Chloride or Arginine Chloride Required
Description	Total doses of potassium chloride or arginine chloride given during the first five postoperative days.
Time Frame	Postop day 0-5

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Furosemide	Peritoneal Dialysis
Arm/Group Description	Patients randomized to furosemide	Patients randomized to peritoneal dialysis
Measure Participants	32	41
Median (Inter-Quartile Range) [doses given]	2	1

9. Secondary Outcome

Title	B-Natriuretic Peptide
Description	BNP measured at 24 and 48 hours postoperatively
Time Frame	At 24hours and 48 hours postoperative

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Furosemide	Peritoneal Dialysis
Arm/Group Description	Patients randomized to furosemide	Patients randomized to peritoneal dialysis
Measure Participants	32	41
24 hours	1334	1168
48 hours	1110	663

10. Secondary Outcome

Title	Modified Oxygenation Index
Description	Product of Mean airway pressure delivered by mechanical ventilation and FiO2 of administered oxygen
Time Frame	at 24 and 48 hours postoperative

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Furosemide	Peritoneal Dialysis
Arm/Group Description	Patients randomized to furosemide	Patients randomized to PD
Measure Participants	32	41
24 Hours	4	4
48 Hours	3.8	2.8

Adverse Events

Arm/Group Title	Furosemide		Peritoneal Dialysis
Arm/Group Description	Patients randomized to furosemide		Patients randomized to peritoneal dialysis
All Cause Mortality
	Furosemide		Peritoneal Dialysis
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/32 (9.4%)		1/41 (2.4%)
Serious Adverse Events
	Furosemide		Peritoneal Dialysis
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/32 (0%)		0/41 (0%)
Other (Not Including Serious) Adverse Events
	Furosemide		Peritoneal Dialysis
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/32 (0%)		2/41 (4.9%)
Blood and lymphatic system disorders
Bleeding Event	0/32 (0%)	0	1/41 (2.4%)	1
Skin and subcutaneous tissue disorders
Hydrocele	0/32 (0%)	0	1/41 (2.4%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.