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Inability to recruit patients
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The investigators will conduct a prospective, blinded, randomized, placebo-controlled trial with a sample size of 20 patients in each of the two arms (fenoldopam vs placebo) based upon a difference in serum creatinine by one standard deviation. Fluid and salt intake will be held constant within clinical parameters and carefully measured. Fenoldopam will be started at 0.1 ug/kg/min. If, after 6 hrs there is no decrease in blood pressure, the dose will be increased to 0.2 ug/kg/min. This dose will be continued throughout the remainder of the study. A study of pediatric patients previously provided to the FDA showed no hypotension at a dose of 0.2 ug/kg/min. Fenoldopam will be started 12 hrs before the first dose of indomethacin and discontinued 12 hrs after the 3rd dose of indomethacin. Study samples will include both blood and urine. The primary outcome will be a reduction in renal dysfunction, as determined by creatinine and urine output over the course of treatment. Additional outcomes will include determination of known and novel metabolomic urine markers of renal dysfunction.
Hypotheses
Specific Aims
Study design
Describe study population or sample material
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Control | Placebo Comparator | Infants in the Placebo arm will receive 0.9% sodium chloride (0.1 ml/hr). If, after 6 hrs there is not a clinically concerning decrease in blood pressure, as determined by attending physician, the rate of infusion (in this arm the placebo) will be increased to 0.2 ml/kg/hr. This rate will be continued throughout the remainder of the study. |
|
| Fenoldopam | Experimental | Infants in the experimental arm will receive fenoldopam (60 ug/ml; 0.1 ml/hr to provide 0.1ug/kg/min). If, after 6 hrs there is not a clinically concerning decrease in blood pressure, as determined by attending physician, the rate of infusion will be increased to 0.2 ml/kg/hr (0.2 ug/kg/min for infants receiving fenoldopam). This rate will be continued throughout the remainder of the study. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fenoldopam | Drug | Randomized to receive Fenoldopam or 0.9%NS |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in Urine Output (ml/kg/hr) | Urine will be collected and measured in 6 hour increments beginning 6 hours prior to starting fenoldopam or placebo infusion. The first dose of indomethacin will be given 12 hours after starting fenoldopam or placebo. Two additional doses of indomethacin will be given 12 hours apart. Urine will continue to be collected and volume measured in 6 hour increments up to 24 hrs after the last dose of indomethacin. To summarize, urine will be collected and measured from time -6 hours to 0 hours. Fenoldapam or placebo will be initiated at time 0 hrs, indomethacin given at time 12, 24 and 36 hours, and urine collected and measured to time 60 hours. | 66 hrs - from 6 hrs before beginning of fenoldopam or placebo infusion up to 24 hours after the last dose of indomethacin |
| Serum Levels of Fenoldopam During Infusion of the Drug and Following Discontinuation of the Drug Will be Measured by Liquid Chromatography and Mass Spectroscopy. | Blood samples for determination of serum fenoldopam levels will be obtained immediately prior to starting the infusion of fenoldopam (time 0 hour), continue through the 48 hour period of fenoldopam infusion and continue for an additional 12 hours after stopping the fenoldopam infusion. | 60 hours |
| Change in Levels of Serum Albumin (mg/dl) | Period from just prior to first dose of indomethacin (time point 12 hours) to 24 hours beyond last dose of indomethacin ( which is time point 60 hours). Thus, this aspect of study takes place between time point 12 hr and time point 60 hr, which is a 48 hour period | 48 hrs |
| Changes in Serum Creatinine (mg/dl) | Serum creatinine will be measured immediately prior to first dose of indomethacin, immediately prior to the third dose of indomethacin (24 hr later) and 24 hours after the third dose of indomethacin | 48 hours |
| Serum Levels of Fenoldopam Will be Related the Changes in Urine Volume |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jeffrey Segar, MD | University of Iowa | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Iowa | Iowa City | Iowa | 52242 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39607014 | Derived | Esezobor CI, Bhatt GC, Effa EE, Hodson EM. Fenoldopam for preventing and treating acute kidney injury. Cochrane Database Syst Rev. 2024 Nov 28;11(11):CD012905. doi: 10.1002/14651858.CD012905.pub2. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Control | Infants in the Placebo arm will receive 0.9% sodium chloride (0.1 ml/hr). If, after 6 hrs there is not a clinically concerning decrease in blood pressure, as determined by attending physician, the rate of infusion (in this arm the placebo) will be increased to 0.2 ml/kg/hr. This rate will be continued throughout the remainder of the study. 0.9%NS: Randomized to receive Fenoldopam or 0.9%NS |
| FG001 | Fenoldopam | Infants in the experimental arm will receive fenoldopam (60 ug/ml; 0.1 ml/hr to provide 0.1ug/kg/min). If, after 6 hrs there is not a clinically concerning decrease in blood pressure, as determined by attending physician, the rate of infusion will be increased to 0.2 ml/kg/hr (0.2 ug/kg/min for infants receiving fenoldopam). This rate will be continued throughout the remainder of the study. Fenoldopam: Randomized to receive Fenoldopam or 0.9%NS |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
No analysis performed as only a single patient was enrolled
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| ID | Title | Description |
|---|---|---|
| BG000 | Control | Infants in the Placebo arm will receive 0.9% sodium chloride (0.1 ml/hr). If, after 6 hrs there is not a clinically concerning decrease in blood pressure, as determined by attending physician, the rate of infusion (in this arm the placebo) will be increased to 0.2 ml/kg/hr. This rate will be continued throughout the remainder of the study. 0.9%NS: Randomized to receive Fenoldopam or 0.9%NS |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Changes in Urine Output (ml/kg/hr) | Urine will be collected and measured in 6 hour increments beginning 6 hours prior to starting fenoldopam or placebo infusion. The first dose of indomethacin will be given 12 hours after starting fenoldopam or placebo. Two additional doses of indomethacin will be given 12 hours apart. Urine will continue to be collected and volume measured in 6 hour increments up to 24 hrs after the last dose of indomethacin. To summarize, urine will be collected and measured from time -6 hours to 0 hours. Fenoldapam or placebo will be initiated at time 0 hrs, indomethacin given at time 12, 24 and 36 hours, and urine collected and measured to time 60 hours. | No analysis performed as only single patient was enrolled | Posted | 66 hrs - from 6 hrs before beginning of fenoldopam or placebo infusion up to 24 hours after the last dose of indomethacin |
|
Two weeks
All-Cause Mortality, Serious, and Other (Not Including Serious) Adverse Events as per clinicaltrial.gov definitions
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Control | Infants in the Placebo arm will receive 0.9% sodium chloride (0.1 ml/hr). If, after 6 hrs there is not a clinically concerning decrease in blood pressure, as determined by attending physician, the rate of infusion (in this arm the placebo) will be increased to 0.2 ml/kg/hr. This rate will be continued throughout the remainder of the study. 0.9%NS: Randomized to receive Fenoldopam or 0.9%NS |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jeffrey Segar | Medical College of Wisconsin | 14143377702 | jsegar@mcw.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 26, 2018 | Nov 22, 2021 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D004374 | Ductus Arteriosus, Patent |
| D058186 | Acute Kidney Injury |
| ID | Term |
|---|---|
| D006330 | Heart Defects, Congenital |
| D018376 | Cardiovascular Abnormalities |
| D002318 | Cardiovascular Diseases |
| D006331 | Heart Diseases |
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| ID | Term |
|---|---|
| D018818 | Fenoldopam |
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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| 0.9%NS |
| Drug |
Randomized to receive Fenoldopam or 0.9%NS |
|
|
We will relate serum levels of fenoldopam to changes in urine volume over the duration of time of fenoldopam infusion and after discontinuation of infusion. This constitutes part of the pharmacodynamic analysis |
| 60 hours |
| Serum Levels of Fenoldopam Will be Related to Absolute and Relative Changes in Serum Creatinine | We will relate serum levels of fenoldopam to serum creatinine values over the duration of time of fenoldopam infusion and after discontinuation of infusion. This constitutes part of the pharmacodynamic analysis | 60 hours |
| Change in Levels of Serum Beta 2 Macroglobulin (mcg/ml) | Period from just prior to first dose of indomethacin (time point 12 hours) to 24 hours beyond last dose of indomethacin ( which is time point 60 hours). Thus, this aspect of study takes place between time point 12 hr and time point 60 hr, which is a 48 hour period | 48 hrs |
| Change in Levels of Serum Cystatin C (mcg/ml) | Period from just prior to first dose of indomethacin (time point 12 hours) to 24 hours beyond last dose of indomethacin ( which is time point 60 hours). Thus, this aspect of study takes place between time point 12 hr and time point 60 hr, which is a 48 hour period | 48 hrs |
| Change in Levels of Serum Epidermal Growth Factor (EGF) (ng/ml) | Period from just prior to first dose of indomethacin (time point 12 hours) to 24 hours beyond last dose of indomethacin ( which is time point 60 hours). Thus, this aspect of study takes place between time point 12 hr and time point 60 hr, which is a 48 hour period | 48 hrs |
| Change in Levels of Serum Osteopontin (ng/ml) | Period from just prior to first dose of indomethacin (time point 12 hours) to 24 hours beyond last dose of indomethacin ( which is time point 60 hours). Thus, this aspect of study takes place between time point 12 hr and time point 60 hr, which is a 48 hour period | 48 hrs |
| Change in Levels of Serum Uromodulin (mg/dl) | Period from just prior to first dose of indomethacin (time point 12 hours) to 24 hours beyond last dose of indomethacin ( which is time point 60 hours). Thus, this aspect of study takes place between time point 12 hr and time point 60 hr, which is a 48 hour period | 48 hrs |
| Change in Level of Urine Albumin (mg/dl) | Period from just prior to first dose of indomethacin (time point 12 hours) to 24 hours beyond last dose of indomethacin ( which is time point 60 hours). Thus, this aspect of study takes place between time point 12 hr and time point 60 hr, which is a 48 hour period | 48 hr |
| Change in Level of Urine Beta 2 Macroglobulin (mcg/ml) | Period from just prior to first dose of indomethacin (time point 12 hours) to 24 hours beyond last dose of indomethacin ( which is time point 60 hours). Thus, this aspect of study takes place between time point 12 hr and time point 60 hr, which is a 48 hour period | 48 hrs |
| Change in Level of Urine Cystatin C (mcg/ml) | Period from just prior to first dose of indomethacin (time point 12 hours) to 24 hours beyond last dose of indomethacin ( which is time point 60 hours). Thus, this aspect of study takes place between time point 12 hr and time point 60 hr, which is a 48 hour period | 48 hr |
| Change in Levels of Urine Epidermal Growth Factor (EGF) (ng/ml) | Period from just prior to first dose of indomethacin (time point 12 hours) to 24 hours beyond last dose of indomethacin ( which is time point 60 hours). Thus, this aspect of study takes place between time point 12 hr and time point 60 hr, which is a 48 hour period | 48 hr |
| Change in Levels of Urine Osteopontin (ng/ml) | Period from just prior to first dose of indomethacin (time point 12 hours) to 24 hours beyond last dose of indomethacin ( which is time point 60 hours). Thus, this aspect of study takes place between time point 12 hr and time point 60 hr, which is a 48 hour period | 48 hrs |
| Change in Levels of Urine Uromodulin (mg/dl) | Period from just prior to first dose of indomethacin (time point 12 hours) to 24 hours beyond last dose of indomethacin ( which is time point 60 hours). Thus, this aspect of study takes place between time point 12 hr and time point 60 hr, which is a 48 hour period | 48 hrs |
| BG001 | Fenoldopam | Infants in the experimental arm will receive fenoldopam (60 ug/ml; 0.1 ml/hr to provide 0.1ug/kg/min). If, after 6 hrs there is not a clinically concerning decrease in blood pressure, as determined by attending physician, the rate of infusion will be increased to 0.2 ml/kg/hr (0.2 ug/kg/min for infants receiving fenoldopam). This rate will be continued throughout the remainder of the study. Fenoldopam: Randomized to receive Fenoldopam or 0.9%NS |
| BG002 | Total | Total of all reporting groups |
| weeks gestation |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG001 | Fenoldopam | Infants in the experimental arm will receive fenoldopam (60 ug/ml; 0.1 ml/hr to provide 0.1ug/kg/min). If, after 6 hrs there is not a clinically concerning decrease in blood pressure, as determined by attending physician, the rate of infusion will be increased to 0.2 ml/kg/hr (0.2 ug/kg/min for infants receiving fenoldopam). This rate will be continued throughout the remainder of the study. Fenoldopam: Randomized to receive Fenoldopam or 0.9%NS |
|
| Primary | Serum Levels of Fenoldopam During Infusion of the Drug and Following Discontinuation of the Drug Will be Measured by Liquid Chromatography and Mass Spectroscopy. | Blood samples for determination of serum fenoldopam levels will be obtained immediately prior to starting the infusion of fenoldopam (time 0 hour), continue through the 48 hour period of fenoldopam infusion and continue for an additional 12 hours after stopping the fenoldopam infusion. | No analysis performed as only single patient was enrolled | Posted | 60 hours |
|
|
| Primary | Change in Levels of Serum Albumin (mg/dl) | Period from just prior to first dose of indomethacin (time point 12 hours) to 24 hours beyond last dose of indomethacin ( which is time point 60 hours). Thus, this aspect of study takes place between time point 12 hr and time point 60 hr, which is a 48 hour period | No analysis performed as only single patient was enrolled | Posted | 48 hrs |
|
|
| Primary | Changes in Serum Creatinine (mg/dl) | Serum creatinine will be measured immediately prior to first dose of indomethacin, immediately prior to the third dose of indomethacin (24 hr later) and 24 hours after the third dose of indomethacin | No analysis performed as only single patient was enrolled | Posted | 48 hours |
|
|
| Primary | Serum Levels of Fenoldopam Will be Related the Changes in Urine Volume | We will relate serum levels of fenoldopam to changes in urine volume over the duration of time of fenoldopam infusion and after discontinuation of infusion. This constitutes part of the pharmacodynamic analysis | No analysis performed as only single patient was enrolled | Posted | 60 hours |
|
|
| Primary | Serum Levels of Fenoldopam Will be Related to Absolute and Relative Changes in Serum Creatinine | We will relate serum levels of fenoldopam to serum creatinine values over the duration of time of fenoldopam infusion and after discontinuation of infusion. This constitutes part of the pharmacodynamic analysis | No analysis performed as only single patient was enrolled | Posted | 60 hours |
|
|
| Primary | Change in Levels of Serum Beta 2 Macroglobulin (mcg/ml) | Period from just prior to first dose of indomethacin (time point 12 hours) to 24 hours beyond last dose of indomethacin ( which is time point 60 hours). Thus, this aspect of study takes place between time point 12 hr and time point 60 hr, which is a 48 hour period | No analysis performed as only single patient was enrolled | Posted | 48 hrs |
|
|
| Primary | Change in Levels of Serum Cystatin C (mcg/ml) | Period from just prior to first dose of indomethacin (time point 12 hours) to 24 hours beyond last dose of indomethacin ( which is time point 60 hours). Thus, this aspect of study takes place between time point 12 hr and time point 60 hr, which is a 48 hour period | No analysis performed as only single patient was enrolled | Posted | 48 hrs |
|
|
| Primary | Change in Levels of Serum Epidermal Growth Factor (EGF) (ng/ml) | Period from just prior to first dose of indomethacin (time point 12 hours) to 24 hours beyond last dose of indomethacin ( which is time point 60 hours). Thus, this aspect of study takes place between time point 12 hr and time point 60 hr, which is a 48 hour period | No analysis performed as only single patient was enrolled | Posted | 48 hrs |
|
|
| Primary | Change in Levels of Serum Osteopontin (ng/ml) | Period from just prior to first dose of indomethacin (time point 12 hours) to 24 hours beyond last dose of indomethacin ( which is time point 60 hours). Thus, this aspect of study takes place between time point 12 hr and time point 60 hr, which is a 48 hour period | No analysis performed as only single patient was enrolled | Posted | 48 hrs |
|
|
| Primary | Change in Levels of Serum Uromodulin (mg/dl) | Period from just prior to first dose of indomethacin (time point 12 hours) to 24 hours beyond last dose of indomethacin ( which is time point 60 hours). Thus, this aspect of study takes place between time point 12 hr and time point 60 hr, which is a 48 hour period | No analysis performed as only single patient was enrolled | Posted | 48 hrs |
|
|
| Primary | Change in Level of Urine Albumin (mg/dl) | Period from just prior to first dose of indomethacin (time point 12 hours) to 24 hours beyond last dose of indomethacin ( which is time point 60 hours). Thus, this aspect of study takes place between time point 12 hr and time point 60 hr, which is a 48 hour period | No analysis performed as only single patient was enrolled | Posted | 48 hr |
|
|
| Primary | Change in Level of Urine Beta 2 Macroglobulin (mcg/ml) | Period from just prior to first dose of indomethacin (time point 12 hours) to 24 hours beyond last dose of indomethacin ( which is time point 60 hours). Thus, this aspect of study takes place between time point 12 hr and time point 60 hr, which is a 48 hour period | No analysis performed as only single patient was enrolled | Posted | 48 hrs |
|
|
| Primary | Change in Level of Urine Cystatin C (mcg/ml) | Period from just prior to first dose of indomethacin (time point 12 hours) to 24 hours beyond last dose of indomethacin ( which is time point 60 hours). Thus, this aspect of study takes place between time point 12 hr and time point 60 hr, which is a 48 hour period | No analysis performed as only single patient was enrolled | Posted | 48 hr |
|
|
| Primary | Change in Levels of Urine Epidermal Growth Factor (EGF) (ng/ml) | Period from just prior to first dose of indomethacin (time point 12 hours) to 24 hours beyond last dose of indomethacin ( which is time point 60 hours). Thus, this aspect of study takes place between time point 12 hr and time point 60 hr, which is a 48 hour period | No analysis performed as only single patient was enrolled | Posted | 48 hr |
|
|
| Primary | Change in Levels of Urine Osteopontin (ng/ml) | Period from just prior to first dose of indomethacin (time point 12 hours) to 24 hours beyond last dose of indomethacin ( which is time point 60 hours). Thus, this aspect of study takes place between time point 12 hr and time point 60 hr, which is a 48 hour period | No analysis performed as only single patient was enrolled | Posted | 48 hrs |
|
|
| Primary | Change in Levels of Urine Uromodulin (mg/dl) | Period from just prior to first dose of indomethacin (time point 12 hours) to 24 hours beyond last dose of indomethacin ( which is time point 60 hours). Thus, this aspect of study takes place between time point 12 hr and time point 60 hr, which is a 48 hour period | No analysis performed as only single patient was enrolled | Posted | 48 hrs |
|
|
| 0 |
| 1 |
| 0 |
| 1 |
| 0 |
| 1 |
| EG001 | Fenoldopam | Infants in the experimental arm will receive fenoldopam (60 ug/ml; 0.1 ml/hr to provide 0.1ug/kg/min). If, after 6 hrs there is not a clinically concerning decrease in blood pressure, as determined by attending physician, the rate of infusion will be increased to 0.2 ml/kg/hr (0.2 ug/kg/min for infants receiving fenoldopam). This rate will be continued throughout the remainder of the study. Fenoldopam: Randomized to receive Fenoldopam or 0.9%NS | 0 | 0 | 0 | 0 | 0 | 0 |
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| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |