Double-Blind Placebo-Controlled CIN Trial

• Sponsor: University of Michigan (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02467075
• Collaborator: Radiological Society of North America (Other)
• Enrollment: 1
• Location: 1
• Arms: 2
• Actual Duration (Months): 2
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

This double-blinded placebo-controlled study will examine the incidence and significance of contrast-induced acute kidney injury following IV iodine-based contrast material administration in subjects with stage IIIB or stage IV chronic kidney disease.

Subjects will be scheduled for clinically indicated CT of the abdomen and/or pelvis to evaluate for suspected intra-abdominal infection. Subjects will be randomized to receive either weight-based low-osmolality iodinated contrast material or saline. The primary outcome measure will be the incidence of stage II AKI by AKIN (Acute Kidney Injury Network) criteria.

Condition or Disease	Intervention/Treatment	Phase
Acute Kidney Injury	Drug: Iopamidol 300 (Contrast); Drug: Placebo (Normal Saline)	Phase 4

Detailed Description

This double-blinded placebo-controlled non-inferiority study will examine the incidence and significance of contrast-induced acute kidney injury following intravenous iodine-based contrast material administration in subjects with stage IIIB or stage IV chronic kidney disease.

Subjects will be scheduled for clinically indicated CT of the abdomen and/or pelvis to evaluate for suspected intra-abdominal infection. Subjects will be randomized to receive either weight-based low-osmolality iodinated contrast material or saline. The primary outcome measure will be the incidence of stage II AKI by AKIN criteria.

Secondary outcome measures will include AKI by other definitions (stage I AKI, traditional CI-AKI definition), hospital length of stay, 30-day readmission rate, number of additional percutaneous interventions within 30 days, number of additional CT examinations within 30 days, and 30-day mortality rate. All subjects will receive a minimum of 1 mL/kg/hr (max: 125 mL/hr) of volume expansion for at least three hours before and after the CT..

Study Design

• Study Type: Interventional
• Actual Enrollment: 1 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Other
• Official Title: Phase IV Randomized Double-Blinded Placebo-Controlled Noninferiority Study of the Effect of Intravenous Low-Osmolality Iodinated Contrast Material On Renal Function in Postoperative Adults With Stage IIIb or Stage IV Chronic Kidney Disease
• Actual Study Start Date: Jul 1, 2015
• Actual Primary Completion Date: Sep 1, 2015
• Actual Study Completion Date: Sep 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Iopamidol 300 (Contrast) Subjects scheduled for a clinical CT will be randomized to receive weight-based low-osmolality iodinated contrast with the CT. All subjects will receive a minimum of 1 mL/kg/hr of isotonic volume expansion for at least three hours before and three hours after the CT.	Drug: Iopamidol 300 (Contrast); Patients will be randomized to receive IV iopamidol 300 (1.25 mL/kg, max 125 mL) with their CT scan
Placebo Comparator: Placebo (Normal Saline) Subjects scheduled for a standard of care CT will be randomized to receive weight-based normal saline instead of contrast material with the CT. All subjects will receive a minimum of 1 mL/kg/hr of isotonic volume expansion for at least three hours before and three hours after the CT.	Drug: Placebo (Normal Saline); Patients will be randomized to receive IV normal saline (1.25 mL/kg, max 125 mL) with their CT scan; Other Names: Normal saline

Outcome Measures

Primary Outcome Measures

1. Participants With Stage II AKI (Acute Kidney Injury) [48 hours]

   Participants who had Stage II AKI. This is measured by comparing an initial blood creatinine level with the level at 48 hours. Creatine is a chemical waste product that passes through the kidneys. Creatinine levels reflect how well the kidneys are working.

Secondary Outcome Measures

1. Subjects With AKI (Acute Kidney Injury), Stage 1 or Other Definition [48-72 hours]

   Stage I AKI, traditional CIN definitions or other definitions of AKI (acute kidney injury) at lower levels of severity

2. Subjects Requiring Renal Replacement Therapy (Kidney Transplant or Dialysis) [30 days]

   Number of subjects that require renal (kidney) replacement therapy, such as a kidney transplant or dialysis within 30 days of study participation.

3. Hospital Length of Stay [Duration of hospital stay (assessed from date of randomization up to 30 days)]

   Subject's hospital length of stay in days

4. 30-day Readmission [30 days]

   Number of times a subject is readmitted within 30 days of study recruitment

5. Mortality Rate - 30 Day [30 days]

   Number of subjects who died within 30 days of entry into the study.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Inpatients scheduled for CT scan of abdomen and/or pelvis

• Had surgery in the last 4 weeks

• Stable renal function (based on serum creatinine-last two lab values +/- 0.3 of each other, with most recent within 5 days of CT)

• Suspected infection or fluid collection in abdomen and/or pelvis

Exclusion Criteria:

• Pregnant

• Severe Allergy (anaphylaxis) to contrast

• Dialysis in last 7 days

• Received intravascular iodinated contrast in last 48 hours

• CT of abdomen and pelvis in last 7 days shows no fluid collection

• Prisoners

• CT ordered for an indication that requires (eg, CT angiogram) or contraindicates (eg, renal stone CT) the administration of intravascular contrast

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Michigan Hospital Department of Radiology	Ann Arbor	Michigan	United States	48109

Sponsors and Collaborators

• University of Michigan
• Radiological Society of North America

Investigators

• Principal Investigator: Matthew Davenport, MD, University of Michigan

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Matthew Davenport, MD, Assistant Professor, University of Michigan
• ClinicalTrials.gov Identifier: NCT02467075
• Other Study ID Numbers: HUM 00097944
• First Posted: Jun 9, 2015
• Last Update Posted: Jun 27, 2017
• Last Verified: May 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Matthew Davenport, MD, Assistant Professor, University of Michigan: CT, iodinated contrast, contrast-induced AKI, kidney injury
• Additional relevant MeSH terms: Acute Kidney Injury

Study Results

Participant Flow

Recruitment Details	Subjects were recruited from inpatients at a tertiary medical center who were scheduled to have a clinical CT for a suspected infection. Subjects had to have a previous diagnosis of Chronic Kidney Disease (CKD) Stage II or IIB and stable creatinine levels. Their physician had to agree to their participation in the study.
Pre-assignment Detail	Patients had to be scheduled for a CT that did not have a) requirement for the CT scan to be performed with contrast agent or b) a contraindication against having the CT scan with contrast agent

Arm/Group Title	Iopamidol 300 (Contrast)	Placebo (Normal Saline)
Arm/Group Description	Subjects scheduled for a clinical CT will be randomized to receive weight-based low-osmolality iodinated contrast with the CT. All subjects will receive a minimum of 1 mL/kg/hr of isotonic volume expansion for at least 3 hours before and 3 hours after the CT. The function of the fluids is to minimize the effect of the contrast on their creatinine level. Iopamidol 300 (Contrast): Patients will be randomized to receive IV iopamidol 300 (1.25 mL/kg, up to a max volume of 125 mL) with their CT scan	Subjects scheduled for a clinical CT will be randomized to receive normal saline instead of contrast material with the CT. All subjects will receive a minimum of 1 mL/kg/hr of isotonic volume expansion for at least 3 hours before and 3 hours after the CT. The fluids are given to placebo patients in order to minimize any differences in treatment between the treatment and placebo groups. Placebo (Normal Saline): Patients will be randomized to receive IV normal saline (1.25 mL/kg, up to a max volume of 125 mL) with their CT scan
Period Title: Initial CT Scan
STARTED	0	1
COMPLETED	0	1
NOT COMPLETED	0	0
Period Title: Initial CT Scan
STARTED	0	1
COMPLETED	0	1
NOT COMPLETED	0	0
Period Title: Initial CT Scan
STARTED	0	1
COMPLETED	0	1
NOT COMPLETED	0	0
Period Title: Initial CT Scan
STARTED	0	1
COMPLETED	0	1
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Iopamidol 300 (Contrast)	Placebo (Normal Saline)	Total
Arm/Group Description	Subjects scheduled for a clinical CT will be randomized to receive weight-based low-osmolality iodinated contrast with the CT. All subjects will receive a minimum of 1 mL/kg/hr of isotonic volume expansion for at least three hours before and three hours after the CT. Iopamidol 300 (Contrast): Patients will be randomized to receive IV iopamidol 300 (1.25 mL/kg, max 125 mL) with their CT scan	Subjects scheduled for a standard of care CT will be randomized to receive weight-based normal saline instead of contrast material with the CT. All subjects will receive a minimum of 1 mL/kg/hr of isotonic volume expansion for at least three hours before and three hours after the CT. Placebo (Normal Saline): Patients will be randomized to receive IV normal saline (1.25 mL/kg, max 125 mL) with their CT scan	Total of all reporting groups
Overall Participants	0	1	1
Age (Count of Participants)
<=18 years	0 NaN	0 0%	0 0%
Between 18 and 65 years	0 NaN	0 0%	0 0%
>=65 years	0 NaN	1 100%	1 100%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	84	84
Sex: Female, Male (Count of Participants)
Female	0 NaN	0 0%	0 0%
Male	0 NaN	1 100%	1 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 NaN	0 0%	0 0%
Asian	0 NaN	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 NaN	0 0%	0 0%
Black or African American	0 NaN	0 0%	0 0%
White	0 NaN	1 100%	1 100%
More than one race	0 NaN	0 0%	0 0%
Unknown or Not Reported	0 NaN	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	1 Infinity	1 100%

Outcome Measures

1. Primary Outcome

Title	Participants With Stage II AKI (Acute Kidney Injury)
Description	Participants who had Stage II AKI. This is measured by comparing an initial blood creatinine level with the level at 48 hours. Creatine is a chemical waste product that passes through the kidneys. Creatinine levels reflect how well the kidneys are working.
Time Frame	48 hours

Outcome Measure Data

Analysis Population Description

Participants with State II AKI (Acute Kidney Injury)

Arm/Group Title	Iopamidol 300 (Contrast)	Placebo (Normal Saline)
Arm/Group Description	Subjects scheduled for a clinical CT will be randomized to receive weight-based low-osmolality iodinated contrast with the CT. All subjects will receive a minimum of 1 mL/kg/hr of isotonic volume expansion for at least three hours before and three hours after the CT. Iopamidol 300 (Contrast): Patients will be randomized to receive IV iopamidol 300 (1.25 mL/kg, max 125 mL) with their CT scan	Subjects scheduled for a standard of care CT will be randomized to receive weight-based normal saline instead of contrast material with the CT. All subjects will receive a minimum of 1 mL/kg/hr of isotonic volume expansion for at least three hours before and three hours after the CT. Placebo (Normal Saline): Patients will be randomized to receive IV normal saline (1.25 mL/kg, max 125 mL) with their CT scan
Measure Participants	0	1
Count of Participants [Participants]	0 NaN	0 0%

2. Secondary Outcome

Title	Subjects With AKI (Acute Kidney Injury), Stage 1 or Other Definition
Description	Stage I AKI, traditional CIN definitions or other definitions of AKI (acute kidney injury) at lower levels of severity
Time Frame	48-72 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Iopamidol 300 (Contrast)	Placebo (Normal Saline)
Arm/Group Description	Subjects scheduled for a clinical CT were randomized to receive weight-based low-osmolality iodinated contrast with the CT. All subjects will receive a minimum of 1 mL/kg/hr of isotonic volume expansion for at least 3 hours before and 3 hours after the CT. Iopamidol 300 (Contrast): Patients will be randomized to receive IV iopamidol 300 (1.25 mL/kg, up to a max volume of 125 mL) with their CT scan	Subjects scheduled for a clinical CT were randomized to receive weight-based normal saline instead of contrast material with the CT. All subjects will receive a minimum of 1 mL/kg/hr of isotonic volume expansion for at least 3 hours before and 3 hours after the CT. Placebo (Normal Saline): Patients will be randomized to receive IV normal saline (1.25 mL/kg, up to a max volume of 125 mL) with their CT scan
Measure Participants	0	1
Count of Participants [Participants]	0 NaN	0 0%

3. Secondary Outcome

Title	Subjects Requiring Renal Replacement Therapy (Kidney Transplant or Dialysis)
Description	Number of subjects that require renal (kidney) replacement therapy, such as a kidney transplant or dialysis within 30 days of study participation.
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Iopamidol 300 (Contrast)	Placebo (Normal Saline)
Arm/Group Description	Subjects scheduled for a clinical CT were randomized to receive weight-based low-osmolality iodinated contrast with the CT. All subjects will receive a minimum of 1 mL/kg/hr of isotonic volume expansion for at least 3 hours before and 3 hours after the CT. Iopamidol 300 (Contrast): Patients will be randomized to receive IV iopamidol 300 (1.25 mL/kg, up to a max volume of 125 mL) with their CT scan	Subjects scheduled for a clinical CT were randomized to receive weight-based normal saline instead of contrast material with the CT. All subjects will receive a minimum of 1 mL/kg/hr of isotonic volume expansion for at least 3 hours before and 3 hours after the CT. Placebo (Normal Saline): Patients will be randomized to receive IV normal saline (1.25 mL/kg, up to a max volume of 125 mL) with their CT scan
Measure Participants	0	1
Count of Participants [Participants]	0 NaN	0 0%

4. Secondary Outcome

Title	Hospital Length of Stay
Description	Subject's hospital length of stay in days
Time Frame	Duration of hospital stay (assessed from date of randomization up to 30 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Iopamidol 300 (Contrast)	Placebo (Normal Saline)
Arm/Group Description	Subjects scheduled for a clinical CT were randomized to receive weight-based low-osmolality iodinated contrast with the CT. All subjects will receive a minimum of 1 mL/kg/hr of isotonic volume expansion for at least 3 hours before and 3 hours after the CT. Iopamidol 300 (Contrast): Patients will be randomized to receive IV iopamidol 300 (1.25 mL/kg, up to a max volume of 125 mL) with their CT scan	Subjects scheduled for a clinical CT were randomized to receive weight-based normal saline instead of contrast material with the CT. All subjects will receive a minimum of 1 mL/kg/hr of isotonic volume expansion for at least 3 hours before and 3 hours after the CT. Placebo (Normal Saline): Patients will be randomized to receive IV normal saline (1.25 mL/kg, up to a max volume of 125 mL) with their CT scan
Measure Participants	0	1
Measure days	0	1
Mean (Standard Deviation) [days]	30 (0)

5. Secondary Outcome

Title	30-day Readmission
Description	Number of times a subject is readmitted within 30 days of study recruitment
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Iopamidol 300 (Contrast)	Placebo (Normal Saline)
Arm/Group Description	Subjects scheduled for a clinical CT will be randomized to receive weight-based low-osmolality iodinated contrast with the CT. All subjects will receive a minimum of 1 mL/kg/hr of isotonic volume expansion for at least three hours before and three hours after the CT. Iopamidol 300 (Contrast): Patients will be randomized to receive IV iopamidol 300 (1.25 mL/kg, max 125 mL) with their CT scan	Subjects scheduled for a standard of care CT will be randomized to receive weight-based normal saline instead of contrast material with the CT. All subjects will receive a minimum of 1 mL/kg/hr of isotonic volume expansion for at least three hours before and three hours after the CT. Placebo (Normal Saline): Patients will be randomized to receive IV normal saline (1.25 mL/kg, max 125 mL) with their CT scan
Measure Participants	0	1
Mean (Standard Deviation) [Number of admissions]	0 (0)

6. Secondary Outcome

Title	Mortality Rate - 30 Day
Description	Number of subjects who died within 30 days of entry into the study.
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Iopamidol 300 (Contrast)	Placebo (Normal Saline)
Arm/Group Description	Subjects scheduled for a clinical CT will be randomized to receive weight-based low-osmolality iodinated contrast with the CT. All subjects will receive a minimum of 1 mL/kg/hr of isotonic volume expansion for at least three hours before and three hours after the CT. Iopamidol 300 (Contrast): Patients will be randomized to receive IV iopamidol 300 (1.25 mL/kg, max 125 mL) with their CT scan	Subjects scheduled for a standard of care CT will be randomized to receive weight-based normal saline instead of contrast material with the CT. All subjects will receive a minimum of 1 mL/kg/hr of isotonic volume expansion for at least three hours before and three hours after the CT. Placebo (Normal Saline): Patients will be randomized to receive IV normal saline (1.25 mL/kg, max 125 mL) with their CT scan
Measure Participants	0	1
Number [participants]	0 NaN

Adverse Events

Time Frame	Subjects were followed for 30 days
Adverse Event Reporting Description	The same definitions of adverse events and serious adverse events has been used.
Arm/Group Title	Iopamidol 300 (Contrast)		Placebo (Normal Saline)
Arm/Group Description	Subjects scheduled for a clinical CT were randomized to receive weight-based low-osmolality iodinated contrast with the CT. All subjects will receive a minimum of 1 mL/kg/hr of isotonic volume expansion for at least 3 hours before and 3 hours after the CT. Iopamidol 300 (Contrast): Patients will be randomized to receive IV iopamidol 300 (1.25 mL/kg, up to a max volume of 125 mL) with their CT scan		Subjects scheduled for a clinical CT were randomized to receive weight-based normal saline instead of contrast material with the CT. All subjects will receive a minimum of 1 mL/kg/hr of isotonic volume expansion for at least 3 hours before and 3 hours after the CT. Placebo (Normal Saline): Patients will be randomized to receive IV normal saline (1.25 mL/kg, up to a max volume of 125 mL) with their CT scan
All Cause Mortality
	Iopamidol 300 (Contrast)		Placebo (Normal Saline)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/1 (0%)
Serious Adverse Events
	Iopamidol 300 (Contrast)		Placebo (Normal Saline)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/1 (0%)
Other (Not Including Serious) Adverse Events
	Iopamidol 300 (Contrast)		Placebo (Normal Saline)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/1 (0%)

Limitations/Caveats

The decision to terminate the study due to low accrual potential was made in February 2016, but last data collection from the 1 subject was in September 2015.

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.