Acute Kidney InjuryNCT03902483
Renal Doppler Ultrasound in Early Detection of Acute Kidney Injury in Critically Ill Patients
An observational study of Acute Kidney Injury, run by Assiut University.
Trial summary
Acute kidney injury is a common complication of critical illness and is associated with high morbidity and mortality .Acute kidney injury is a syndrome that is characterized by a rapid decline in renal function and urine output, resulting in retention of waste products such as urea, nitrogen, and serum creatinine. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Acute Kidney Injury
- What is being tested?
- renal doppler ultrasound
- Type of treatment
- Medical device
- How many people
- 80 participants
- Where
- No sites listed yet
- Study dates
- 1 Jul 2019to 1 Dec 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Adult, Older adult
Study population: 80 patients of critically ill patients including acute ischaemic insults, patients presenting with septicaemia, hypertension, respiratory failure, coagulation/ haemorrhagic disorders, shock, and liver diseasea and shock. This study will be performed in the 24-bed mixed medical and surgical intensive care unit of the Assiut University Hospital. Sample size calculations will be based on the assumption that patients not developing Acute Kidney Injury would have an RRI of 0.72 and patients developing Acute Kidney Injury would have an Acute Kidney Injury of 0.79 with a standard deviation of 0.11. These calculations were based on the results of other previous studies that reported median values for Acute Kidney Injury and no Acute Kidney Injury
Who may be able to join
- age >18 years ICU admission within 24 hours
Who cannot join
- Poor abdominal echogenicity
- Severe acute or chronic renal insufficiency
- Dialysis dependency, renal transplantation
- Renal artery stenosis, congenital renal diseases ,renal tumor
- Suicidal attempt
- Pregnancy
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Role of Renal Doppler Ultrasound in Early Detection of Acute Kidney Injury in Critically Ill Patients
Acute kidney injury is a common complication of critical illness and is associated with high morbidity and mortality .Acute kidney injury is a syndrome that is characterized by a rapid decline in renal function and urine output, resulting in retention of waste products such as urea, nitrogen, and serum creatinine. Life-threatening consequences include volume overload, hyperkalaemia, and metabolic acidosis . In its severe form, Acute kidney injury requires renal replacement therapy, which is applied in 5±13% of Intensive Care Unit patients
Read the detailed description
The incidence of Acute kidney injury in intensive care unit patients is rising due to the population age increasing, more comorbidities, and a higher prevalence of risk factors. Improved Intensive Care Unit management has, however, significantly diminished morbidity and the mortality of patients who develop Acute kidney injury I. Despite an increase in the number and severity of comorbidities, in-hospital mortality has declined, but the incidence of Acute kidney injury ,and Acute kidney injury requiring renal replacement therapy has increased over time .
There is still some dispute over the characterization of the different types of Acute kidney injury. Classically there are three types of Acute kidney injury: pre-renal, intrinsic renal, and post-renal failure. These are characterized as decreased renal blood flow (in 40-70% of the patients), direct (intrinsic) renal parenchymal damage (in 10-50% of the patients), and obstruction of urine flow which is less common in the ICU (10%), respectively..
In critically ill patients, sepsis and acute kidney injury are very common diseases and are associated with increased hospitalization and elevated in-hospital mortality rates Acute kidney injury is a dynamic process that evolves from an early reversible condition to an established disease and leads to sustained renal impairment, cell death ,and delayed renal recovery .Consequently, prompt resuscitation of the circulation and optimal perfusion pressure are the primary therapies for critically ill patients with Acute kidney injury. These methods are based principally on the appropriate management of intravenous fluid replacement and vasopressor administration under strict hemodynamic monitoring .
Mechanisms of Acute kidney injury comprise renal hypo-perfusion, intra-renal vasoconstriction, inflammation,oxidative stress and nephrotoxicity .An important pathophysiological pathway includes intra renal vasoconstriction and endothelial damage of the microvessels, leading to impaired macro- and microvascular flow, which further aggravates ischemia .
Renal vasoconstriction is an early manifestation of Acute kidney injury. More specifically, ultrasound imaging of the renal arteries can be instrumental in the early detection of Acute kidney injury. Indeed, renal blood flow is decreased at a nearly stage during acute tubular necrosis as a consequence of protracted intra renal vasoconstriction. The renal resistive index , which is used for assessing arterial pulsatility, was shown to correlate with renal vascular resistance . Renal Doppler ultrasound can measure the renal resistive index , a sonographic index that reflects alterations in blood flow profile of the intrarenal arcuate or interlobar arteries. It reflects the relation between the decline in speed loss of flow (flow velocity) between the peak of systole and the end of diastole in (renal) blood vessels: RRI = (peak systolic velocity _end diastolic velocity)/(peak systolic velocity). Normal values are reported between 0.60 and 0.70 with the difference between both kidneys mostly being less than 5% .
The Doppler renal resistive index has been used for years in a variety of clinical settings . Doppler imaging identifies changes in blood flow at the micro-vascular level. Evaluation of the vascular impedance at different sites of the renal parenchyma could provide useful diagnostic and prognostic information. An increase in renal vascular resistance may be an early sensitive sign of hemodynamic deterioration, even in seemingly stable patients.
Measuring flow resistance in the renal circulation, Renal resistive Index (RRI), could become part of vital organ function assessment using Doppler ultrasound. An increased Doppler Renal resistive Index is suggested to not only reflect changes in intra renal perfusion, but also in systemic hemodynamics .
Renal resistive index (RI), determined by Doppler ultrasonography, directly reveals and quantifies modifications in renal vascular resistance .
Aim of the work
The aim is to
- Determine if the resistive Renal Index on ICU admission patients predicts the development of Acute kidney injury during the first week.
- Determine whether resistive Renal Index is related to the severity of Acute kidney injury or not.
Patients and Methods 80 patients of critically ill patients including acute ischaemic insults, patients presenting with septicaemia, hypertension, respiratory failure, coagulation/ haemorrhagic disorders, shock, and liver disease and shock.
This study will be performed in the 24-bed mixed medical and surgical intensive care unit of the Assiut University Hospital.
Sample size calculations will be based on the assumption that patients not developing Acute kidney injury would have an RRI of 0.72 and patients developing Acute kidney injury would have an Acute kidney injury of 0.79 with a standard deviation of 0.11. These calculations were based on the results of other previous studies that reported median values for Acute kidney injury and no Acute kidney injury
AKI was defined according to the Kidney Disease Improving Global Outcome (KDIGO) classification using both creatinine and urine output criteria [20] KDIGO takes changes in creatinine within 48 hours, or a decline in the glomerular filtration rate (GFR) over 7 days, into account. AKI is defined as an increase in sCreat ≥0.3 mg/dL within 48 hours, or an increase in sCreat ≥1.5-times baseline, which is known or presumed to have occurred within the prior 7 days, or a Urine Out put of <0.5 mL/kg/h for 6 hours
Laboratory tests:
- Complete blood count
- Kidney function
- Electrolytes including sodium,potassium, calcium,Phosphorus and uric acid
- Urine analysis 5-24 hrs sodium in urine
Radiological test:
Doppler of both renal arteries with abdominal ultrasound. Renal resistive index was measured with ultrasound-Doppler
- Conditions
- Acute Kidney Injury
- Being tested
- renal doppler ultrasound
- Medical subject headings
- Acute Kidney Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
renal doppler ultrasoundDevice
renal doppler ultrasound measuring renal resistive index
What is being measured
The primary outcome is the main question the study is designed to answer.
Role of Doppler Renal resistative index in early Prediction of acute kidney injury in critically ill patients
Renal resistive index was measured with ultrasound-Doppler using atransparietal 5MHz pulsed-wave Doppler probe. After visualizing the kidney in ultrasound mode and checking for renal abnormalities, an arcuate or interlobar artery will be localized and three successive Doppler measurements at different positions in the kidney (high, middle and low) will be performed, 3 times in each kidney. So a total number of 9 RRI values will be obtained in each kidney.The median value of each section will be used and the 3 median values of each kidney will be averaged. patients developing AKI would have an AKI of 0.79 with a standard deviation of 0.11
Measured: at one day of the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2019
- Study start1 Jul 2019 (estimated)
- Primary completion30 Jun 2020 (estimated)
- Study completion1 Dec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Acute Kidney InjuryStudies of the same condition, open and under way.
- More trials run by Assiut UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, MANAR SALAH AHMED BARAKAT, Assiut University
- Investigators
- abdalla ismael, Study director, Dr.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03902483
- Sponsor's protocol ID
- MSA
- Status last verified
- Apr 2019
- First submitted
- 2 Apr 2019
- Last updated
- 5 Apr 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Bellomo R, Kellum JA, Ronco C. Acute kidney injury. Lancet. 2012 Aug 25;380(9843):756-66. doi: 10.1016/S0140-6736(11)61454-2. Epub 2012 May 21.
PubMed 22617274Hoste EA, Bagshaw SM, Bellomo R, Cely CM, Colman R, Cruz DN, Edipidis K, Forni LG, Gomersall CD, Govil D, Honore PM, Joannes-Boyau O, Joannidis M, Korhonen AM, Lavrentieva A, Mehta RL, Palevsky P, Roessler E, Ronco C, Uchino S, Vazquez JA, Vidal Andrade E, Webb S, Kellum JA. Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study. Intensive Care Med. 2015 Aug;41(8):1411-23. doi: 10.1007/s00134-015-3934-7. Epub 2015 Jul 11.
PubMed 26162677Hilton R. Acute renal failure. BMJ. 2006 Oct 14;333(7572):786-90. doi: 10.1136/bmj.38975.657639.AE. No abstract available.
PubMed 17038736Basile DP, Anderson MD, Sutton TA. Pathophysiology of acute kidney injury. Compr Physiol. 2012 Apr;2(2):1303-53. doi: 10.1002/cphy.c110041.
PubMed 23798302Gomez H, Ince C, De Backer D, Pickkers P, Payen D, Hotchkiss J, Kellum JA. A unified theory of sepsis-induced acute kidney injury: inflammation, microcirculatory dysfunction, bioenergetics, and the tubular cell adaptation to injury. Shock. 2014 Jan;41(1):3-11. doi: 10.1097/SHK.0000000000000052.
PubMed 24346647Spatola L, Andrulli S. Doppler ultrasound in kidney diseases: a key parameter in clinical long-term follow-up. J Ultrasound. 2016 Apr 16;19(4):243-250. doi: 10.1007/s40477-016-0201-x. eCollection 2016 Dec.
PubMed 27965714Leoncini G, Martinoli C, Viazzi F, Ravera M, Parodi D, Ratto E, Vettoretti S, Tomolillo C, Derchi LE, Deferrari G, Pontremoli R. Changes in renal resistive index and urinary albumin excretion in hypertensive patients under long-term treatment with lisinopril or nifedipine GITS. Nephron. 2002 Feb;90(2):169-73. doi: 10.1159/000049038.
PubMed 11818701
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of Renal Doppler Ultrasound in Early Detection of Acute Kidney Injury in Critically Ill Patients
- ClinicalTrials.gov ID
- NCT03902483
- Acronym / sponsor ID
- MSA
- Conditions
- Acute Kidney Injury
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- 1 Jul 2019 (estimated)
- Primary completion
- 30 Jun 2020 (estimated)
- Study completion
- 1 Dec 2021 (estimated)
- First posted
- 4 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Acute kidney injury is a common complication of critical illness and is associated with high morbidity and mortality .Acute kidney injury is a syndrome that is characterized by a rapid decline in renal function and urine output, resulting in retention of waste products such as urea, nitrogen, and serum creatinine. Life-threatening consequences include volume overload, hyperkalaemia, and metabolic acidosis . In its severe form, Acute kidney injury requires renal replacement therapy, which is applied in 5±13% of Intensive Care Unit patients
Detailed description
The incidence of Acute kidney injury in intensive care unit patients is rising due to the population age increasing, more comorbidities, and a higher prevalence of risk factors. Improved Intensive Care Unit management has, however, significantly diminished morbidity and the mortality of patients who develop Acute kidney injury I. Despite an increase in the number and severity of comorbidities, in-hospital mortality has declined, but the incidence of Acute kidney injury ,and Acute kidney injury requiring renal replacement therapy has increased over time .
There is still some dispute over the characterization of the different types of Acute kidney injury. Classically there are three types of Acute kidney injury: pre-renal, intrinsic renal, and post-renal failure. These are characterized as decreased renal blood flow (in 40-70% of the patients), direct (intrinsic) renal parenchymal damage (in 10-50% of the patients), and obstruction of urine flow which is less common in the ICU (10%), respectively..
In critically ill patients, sepsis and acute kidney injury are very common diseases and are associated with increased hospitalization and elevated in-hospital mortality rates Acute kidney injury is a dynamic process that evolves from an early reversible condition to an established disease and leads to sustained renal impairment, cell death ,and delayed renal recovery .Consequently, prompt resuscitation of the circulation and optimal perfusion pressure are the primary therapies for critically ill patients with Acute kidney injury. These methods are based principally on the appropriate management of intravenous fluid replacement and vasopressor administration under strict hemodynamic monitoring .
Mechanisms of Acute kidney injury comprise renal hypo-perfusion, intra-renal vasoconstriction, inflammation,oxidative stress and nephrotoxicity .An important pathophysiological pathway includes intra renal vasoconstriction and endothelial damage of the microvessels, leading to impaired macro- and microvascular flow, which further aggravates ischemia .
Renal vasoconstriction is an early manifestation of Acute kidney injury. More specifically, ultrasound imaging of the renal arteries can be instrumental in the early detection of Acute kidney injury. Indeed, renal blood flow is decreased at a nearly stage during acute tubular necrosis as a consequence of protracted intra renal vasoconstriction. The renal resistive index , which is used for assessing arterial pulsatility, was shown to correlate with renal vascular resistance . Renal Doppler ultrasound can measure the renal resistive index , a sonographic index that reflects alterations in blood flow profile of the intrarenal arcuate or interlobar arteries. It reflects the relation between the decline in speed loss of flow (flow velocity) between the peak of systole and the end of diastole in (renal) blood vessels: RRI = (peak systolic velocity _end diastolic velocity)/(peak systolic velocity). Normal values are reported between 0.60 and 0.70 with the difference between both kidneys mostly being less than 5% .
The Doppler renal resistive index has been used for years in a variety of clinical settings . Doppler imaging identifies changes in blood flow at the micro-vascular level. Evaluation of the vascular impedance at different sites of the renal parenchyma could provide useful diagnostic and prognostic information. An increase in renal vascular resistance may be an early sensitive sign of hemodynamic deterioration, even in seemingly stable patients.
Measuring flow resistance in the renal circulation, Renal resistive Index (RRI), could become part of vital organ function assessment using Doppler ultrasound. An increased Doppler Renal resistive Index is suggested to not only reflect changes in intra renal perfusion, but also in systemic hemodynamics .
Renal resistive index (RI), determined by Doppler ultrasonography, directly reveals and quantifies modifications in renal vascular resistance .
Aim of the work
The aim is to
- Determine if the resistive Renal Index on ICU admission patients predicts the development of Acute kidney injury during the first week.
- Determine whether resistive Renal Index is related to the severity of Acute kidney injury or not.
Patients and Methods 80 patients of critically ill patients including acute ischaemic insults, patients presenting with septicaemia, hypertension, respiratory failure, coagulation/ haemorrhagic disorders, shock, and liver disease and shock.
This study will be performed in the 24-bed mixed medical and surgical intensive care unit of the Assiut University Hospital.
Sample size calculations will be based on the assumption that patients not developing Acute kidney injury would have an RRI of 0.72 and patients developing Acute kidney injury would have an Acute kidney injury of 0.79 with a standard deviation of 0.11. These calculations were based on the results of other previous studies that reported median values for Acute kidney injury and no Acute kidney injury
AKI was defined according to the Kidney Disease Improving Global Outcome (KDIGO) classification using both creatinine and urine output criteria [20] KDIGO takes changes in creatinine within 48 hours, or a decline in the glomerular filtration rate (GFR) over 7 days, into account. AKI is defined as an increase in sCreat ≥0.3 mg/dL within 48 hours, or an increase in sCreat ≥1.5-times baseline, which is known or presumed to have occurred within the prior 7 days, or a Urine Out put of <0.5 mL/kg/h for 6 hours
Laboratory tests:
- Complete blood count
- Kidney function
- Electrolytes including sodium,potassium, calcium,Phosphorus and uric acid
- Urine analysis 5-24 hrs sodium in urine
Radiological test:
Doppler of both renal arteries with abdominal ultrasound. Renal resistive index was measured with ultrasound-Doppler
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- 80 patients of critically ill patients including acute ischaemic insults, patients presenting with septicaemia, hypertension, respiratory failure, coagulation/ haemorrhagic disorders, shock, and liver diseasea and shock. This study will be performed in the 24-bed mixed medical and surgical intensive care unit of the Assiut University Hospital. Sample size calculations will be based on the assumption that patients not developing Acute Kidney Injury would have an RRI of 0.72 and patients developing Acute Kidney Injury would have an Acute Kidney Injury of 0.79 with a standard deviation of 0.11. These calculations were based on the results of other previous studies that reported median values for Acute Kidney Injury and no Acute Kidney Injury
Key inclusion criteria (1 listed)
- age >18 years ICU admission within 24 hours
Key exclusion criteria (6 listed)
- Poor abdominal echogenicity
- Severe acute or chronic renal insufficiency
- Dialysis dependency, renal transplantation
- Renal artery stenosis, congenital renal diseases ,renal tumor
- Suicidal attempt
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| renal doppler ultrasoundrenal doppler ultrasound measuring renal resistive index | Device | – |
Primary outcome
Role of Doppler Renal resistative index in early Prediction of acute kidney injury in critically ill patients
Time frame: at one day of the study
Renal resistive index was measured with ultrasound-Doppler using atransparietal 5MHz pulsed-wave Doppler probe. After visualizing the kidney in ultrasound mode and checking for renal abnormalities, an arcuate or interlobar artery will be localized and three successive Doppler measurements at different positions in the kidney (high, middle and low) will be performed, 3 times in each kidney. So a total number of 9 RRI values will be obtained in each kidney.The median value of each section will be used and the 3 median values of each kidney will be averaged. patients developing AKI would have an AKI of 0.79 with a standard deviation of 0.11
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2019.
- Background: PubMed 22617274Bellomo R, Kellum JA, Ronco C. Acute kidney injury. Lancet. 2012 Aug 25;380(9843):756-66. doi: 10.1016/S0140-6736(11)61454-2. Epub 2012 May 21.
- Background: PubMed 26162677Hoste EA, Bagshaw SM, Bellomo R, Cely CM, Colman R, Cruz DN, Edipidis K, Forni LG, Gomersall CD, Govil D, Honore PM, Joannes-Boyau O, Joannidis M, Korhonen AM, Lavrentieva A, Mehta RL, Palevsky P, Roessler E, Ronco C, Uchino S, Vazquez JA, Vidal Andrade E, Webb S, Kellum JA. Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study. Intensive Care Med. 2015 Aug;41(8):1411-23. doi: 10.1007/s00134-015-3934-7. Epub 2015 Jul 11.
- Background: PubMed 17038736Hilton R. Acute renal failure. BMJ. 2006 Oct 14;333(7572):786-90. doi: 10.1136/bmj.38975.657639.AE. No abstract available.
- Background: PubMed 23798302Basile DP, Anderson MD, Sutton TA. Pathophysiology of acute kidney injury. Compr Physiol. 2012 Apr;2(2):1303-53. doi: 10.1002/cphy.c110041.
- Background: PubMed 24346647Gomez H, Ince C, De Backer D, Pickkers P, Payen D, Hotchkiss J, Kellum JA. A unified theory of sepsis-induced acute kidney injury: inflammation, microcirculatory dysfunction, bioenergetics, and the tubular cell adaptation to injury. Shock. 2014 Jan;41(1):3-11. doi: 10.1097/SHK.0000000000000052.
- Background: PubMed 27965714Spatola L, Andrulli S. Doppler ultrasound in kidney diseases: a key parameter in clinical long-term follow-up. J Ultrasound. 2016 Apr 16;19(4):243-250. doi: 10.1007/s40477-016-0201-x. eCollection 2016 Dec.
- Background: PubMed 11818701Leoncini G, Martinoli C, Viazzi F, Ravera M, Parodi D, Ratto E, Vettoretti S, Tomolillo C, Derchi LE, Deferrari G, Pontremoli R. Changes in renal resistive index and urinary albumin excretion in hypertensive patients under long-term treatment with lisinopril or nifedipine GITS. Nephron. 2002 Feb;90(2):169-73. doi: 10.1159/000049038.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
abdalla ismael study director
Dr.
Questions about this trial
What is this clinical trial studying?
An observational study of Acute Kidney Injury, run by Assiut University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 5 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact manar salah, resident (01092058750, manarsalah290@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Role of Doppler Renal resistative index in early Prediction of acute kidney injury in critically ill patients (time frame: at one day of the study). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03902483, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Apr 2019.