Acute Kidney InjuryEarly Phase 1NCT02983422
Effects of Aminophylline on Renal Function and Urine Volume of AKI Patient
A Early Phase 1 study testing aminophylline, frusemide and normal saline in people with Acute Kidney Injury, run by Shanghai Jiao Tong University Affiliated Sixth People's Hospital.
Trial summary
This study evaluates the effects of aminophylline on serum creatinine and urine volume of AKI Patient.Half of participants will receive aminophylline and furosemide in combination,while the other half will receive only furosemide. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Kidney Injury
- What is being tested?
- aminophylline, frusemide and normal saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- No sites listed yet
- Study dates
- Dec 2016to Jul 2017
- Phase
- Early Phase 1
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with acute injury (AKI) with no lack of circulating volume (central venous pressure >8cmH2O)
Who cannot join
- Patients with chronic kidney disease
- Patients with acute renal injury caused by insufficient circulating volume
- Patients who do not cooperate with the use of the drug therapy
- Patients who do not cooperate with the relevant examination
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Effects of Aminophylline on Renal Function and Urine Volume Acute Kidney Injury Patient
This study evaluates the effects of aminophylline on serum creatinine and urine volume of AKI Patient.Half of participants will receive aminophylline and furosemide in combination,while the other half will receive only furosemide.
Read the detailed description
Acute kidney injury (AKI) is a sudden perturbation of kidney function that is frequently associated with high morbidity and mortality rates . A diagnostic time limit of 48 hours was recently introduced to ensure early diagnosis, management and prevention of progression to irreversible renal function loss . Furthermore, early AKI biomarkers that can ensure prompt diagnosis have been identified. When these biomarkers become widely available to clinical practice, informed therapeutic interventions capable of aborting disease progression, morbidity and mortality multiplication can be applied . In the injured kidney, adenosine is released endogenously from the macula densa causing vasoconstriction of the renal afferent arterioles via the adenosine A1receptor as well as vasodilatation of the renal efferent arterioles via the adenosine A2 receptor; thereby reducing the renal blood flow and glomerular perfusion pressure leading to ischemic kidney injury . One measure that has been tried with the objective of achieving better AKI outcome is the use of aminophylline (an ethylenediamine coupled theophylline) . Aminophylline is converted to theophylline in the human body, which in turn vasodilates the renal afferent arterioles through competitive inhibition of adenosine on the adenosine A1 receptor.
Aminophylline and theophylline, methylxanthine nonselective adenosine receptor antagonists, have been effective in the management of AKI in certain clinical scenarios including heart failure, calcineurin inhibitor toxicity, and perinatal asphyxia. In the kidney, adenosine constricts the afferent arteriole and decreases glomerular blood flow; adenosine receptor blockade mitigates this vasoconstriction. Aminophylline also inhibits phosphodiesterase at higher concentrations, which leads to increased urine output.
Eligible subjects included all patients more than 18 years old with acute kidney injury in ICU. To ensure the safest oversight for the duration of the study drug infusion, the investigators only approached patients for consent if participants' ICU stay would likely be at least 72 hours . Patients were recruited in the preoperative clinic or in the inpatient ward/ICU; the nature of the consent process for this interventional drug trial necessitated that all procedures were elective or scheduled. Because aminophylline has been associated with tachycardia and seizures at high serum levels, and its metabolism may be affected by liver or thyroid dysfunction and sepsis, the investigators selected the following exclusion criteria: history of tachyarrhythmias, seizures, coagulopathy (international normalized ratio > 1.5 while not taking warfarin),or hypothyroidism. Study investigators or research nurses recruited participants; written, informed consent was signed by each patient or guardian.
The treatment group received aminophylline 5 mg/kg IV load over 30 minutes, followed by 0.5 mg/kg IV every hour, for 72 hours .The control group received placebo bolus followed by IV infusions of normal saline (0.9%) every hour (matched by volume and appearance to the treatment group), for 72 hours.
- Conditions
- Acute Kidney Injury
- Being tested
- aminophylline, frusemide, normal saline
- 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.
aminophyllineDrug
To increase the dose of frusemide until 15mg/h with Syringe pumps. If the urine doesn't reach 1ml/kg/h,then combined with Aminophylline(loading dose of 5mg/kg，and maintenance dose of 0.5mg/kg)
frusemideDrug
Use frusemide with Syringe pumps,maximum dose to 15mg/h
normal salineDrug
Placebo bolus followed by IV infusions of normal saline (0.9%) every hour (matched by volume and appearance to the treatment group)
| Study group | Role | What they receive |
|---|---|---|
| Group aminophylline | Active comparator | To increase the dose of frusemide until 15mg/h with Syringe pumps. If the urine doesn't reach 1ml/kg/h,then combined with Aminophylline(loading dose of 5mg/kg，and maintenance dose of 0.5mg/kg) Receives: Drug: aminophylline; Drug: frusemide |
| Group frusemide | Placebo comparator | Use frusemide with Syringe pumps,maximum dose to 15mg/h，with placebo bolus followed by IV infusions of normal saline (0.9%) every hour (matched by volume and appearance to the treatment group) Receives: Drug: frusemide; Drug: normal saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
serum creatinine
Measured: Change from serum creatinine at 2 weeks
urine volume
Measured: Change from urine volume at 2 weeks
Serum cystatin-C
Measured: Change from Serum cystatin-C at 2 weeks
Urine β_2-microglobulin
Measured: Change from Urine β_2-microglobulin at 2 weeks
Secondary outcomes (3)
dose of norepinephrine
Measured: Change from dose of norepinephrine at 2 weeks
blood pressure
Measured: Change from baseline systolic blood pressure at 2 weeks
central venous pressure
Measured: Change from central venous pressure at 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2016 (estimated)
- Study startDec 2016
- Primary completionJun 2017 (estimated)
- Study completionJul 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Acute Kidney InjuryStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Jiao Tong University Affiliated Sixth People's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Gao Yanding, Shanghai Jiao Tong University Affiliated Sixth People's Hospital
- Investigators
- Xuemin Wang, PhD, Study director, Shanghai 6th People's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02983422
- Sponsor's protocol ID
- SSH-ICU-017
- Status last verified
- Dec 2016
- First submitted
- 26 Nov 2016
- Last updated
- 6 Dec 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Parker MR, Willatts SM. A pilot study to investigate the effects of an infusion of aminophylline on renal function following major abdominal surgery. Anaesthesia. 2001 Jul;56(7):670-5. doi: 10.1046/j.1365-2044.2001.01374.x.
PubMed 11437769Lynch BA, Gal P, Ransom JL, Carlos RQ, Dimaguila MA, Smith MS, Wimmer JE Jr, Imm MD. Low-dose aminophylline for the treatment of neonatal non-oliguric renal failure-case series and review of the literature. J Pediatr Pharmacol Ther. 2008 Apr;13(2):80-7. doi: 10.5863/1551-6776-13.2.80.
PubMed 23055869Yang GZ, Xue FS, Liu GP, Sun C. Use of Aminophylline to Prevent Acute Kidney Injury After Pediatric Cardiac Surgery. Pediatr Crit Care Med. 2016 Aug;17(8):814. doi: 10.1097/PCC.0000000000000838. No abstract available.
PubMed 27500627Chen HH, Anstrom KJ, Givertz MM, Stevenson LW, Semigran MJ, Goldsmith SR, Bart BA, Bull DA, Stehlik J, LeWinter MM, Konstam MA, Huggins GS, Rouleau JL, O'Meara E, Tang WH, Starling RC, Butler J, Deswal A, Felker GM, O'Connor CM, Bonita RE, Margulies KB, Cappola TP, Ofili EO, Mann DL, Davila-Roman VG, McNulty SE, Borlaug BA, Velazquez EJ, Lee KL, Shah MR, Hernandez AF, Braunwald E, Redfield MM; NHLBI Heart Failure Clinical Research Network. Low-dose dopamine or low-dose nesiritide in acute heart failure with renal dysfunction: the ROSE acute heart failure randomized trial. JAMA. 2013 Dec 18;310(23):2533-43. doi: 10.1001/jama.2013.282190.
PubMed 24247300
Study at a glance
From the registry record, last updated by the sponsor on 6 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Aminophylline on Renal Function and Urine Volume Acute Kidney Injury Patient
- ClinicalTrials.gov ID
- NCT02983422
- Acronym / sponsor ID
- SSH-ICU-017
- Conditions
- Acute Kidney Injury
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Shanghai Jiao Tong University Affiliated Sixth People's HospitalUniversity, hospital or other
- Study start
- Dec 2016
- Primary completion
- Jun 2017 (estimated)
- Study completion
- Jul 2017 (estimated)
- First posted
- 6 Dec 2016 (estimated)
- 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.
This study evaluates the effects of aminophylline on serum creatinine and urine volume of AKI Patient.Half of participants will receive aminophylline and furosemide in combination,while the other half will receive only furosemide.
Detailed description
Acute kidney injury (AKI) is a sudden perturbation of kidney function that is frequently associated with high morbidity and mortality rates . A diagnostic time limit of 48 hours was recently introduced to ensure early diagnosis, management and prevention of progression to irreversible renal function loss . Furthermore, early AKI biomarkers that can ensure prompt diagnosis have been identified. When these biomarkers become widely available to clinical practice, informed therapeutic interventions capable of aborting disease progression, morbidity and mortality multiplication can be applied . In the injured kidney, adenosine is released endogenously from the macula densa causing vasoconstriction of the renal afferent arterioles via the adenosine A1receptor as well as vasodilatation of the renal efferent arterioles via the adenosine A2 receptor; thereby reducing the renal blood flow and glomerular perfusion pressure leading to ischemic kidney injury . One measure that has been tried with the objective of achieving better AKI outcome is the use of aminophylline (an ethylenediamine coupled theophylline) . Aminophylline is converted to theophylline in the human body, which in turn vasodilates the renal afferent arterioles through competitive inhibition of adenosine on the adenosine A1 receptor.
Aminophylline and theophylline, methylxanthine nonselective adenosine receptor antagonists, have been effective in the management of AKI in certain clinical scenarios including heart failure, calcineurin inhibitor toxicity, and perinatal asphyxia. In the kidney, adenosine constricts the afferent arteriole and decreases glomerular blood flow; adenosine receptor blockade mitigates this vasoconstriction. Aminophylline also inhibits phosphodiesterase at higher concentrations, which leads to increased urine output.
Eligible subjects included all patients more than 18 years old with acute kidney injury in ICU. To ensure the safest oversight for the duration of the study drug infusion, the investigators only approached patients for consent if participants' ICU stay would likely be at least 72 hours . Patients were recruited in the preoperative clinic or in the inpatient ward/ICU; the nature of the consent process for this interventional drug trial necessitated that all procedures were elective or scheduled. Because aminophylline has been associated with tachycardia and seizures at high serum levels, and its metabolism may be affected by liver or thyroid dysfunction and sepsis, the investigators selected the following exclusion criteria: history of tachyarrhythmias, seizures, coagulopathy (international normalized ratio > 1.5 while not taking warfarin),or hypothyroidism. Study investigators or research nurses recruited participants; written, informed consent was signed by each patient or guardian.
The treatment group received aminophylline 5 mg/kg IV load over 30 minutes, followed by 0.5 mg/kg IV every hour, for 72 hours .The control group received placebo bolus followed by IV infusions of normal saline (0.9%) every hour (matched by volume and appearance to the treatment group), for 72 hours.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group aminophylline | Active comparator | Drug: aminophylline, Drug: frusemideTo increase the dose of frusemide until 15mg/h with Syringe pumps. If the urine doesn't reach 1ml/kg/h,then combined with Aminophylline(loading dose of 5mg/kg，and maintenance dose of 0.5mg/kg) |
| Group frusemide | Placebo comparator | Drug: frusemide, Drug: normal salineUse frusemide with Syringe pumps,maximum dose to 15mg/h，with placebo bolus followed by IV infusions of normal saline (0.9%) every hour (matched by volume and appearance to the treatment group) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Patients with acute injury (AKI) with no lack of circulating volume (central venous pressure >8cmH2O)
Key exclusion criteria (4 listed)
- Patients with chronic kidney disease
- Patients with acute renal injury caused by insufficient circulating volume
- Patients who do not cooperate with the use of the drug therapy
- Patients who do not cooperate with the relevant examination
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 |
|---|---|---|
| aminophyllineTo increase the dose of frusemide until 15mg/h with Syringe pumps. If the urine doesn't reach 1ml/kg/h,then combined with Aminophylline(loading dose of 5mg/kg，and maintenance dose of 0.5mg/kg) | Drug | Group aminophylline |
| frusemideUse frusemide with Syringe pumps,maximum dose to 15mg/h | Drug | Group aminophylline, Group frusemide |
| normal salinePlacebo bolus followed by IV infusions of normal saline (0.9%) every hour (matched by volume and appearance to the treatment group) | Drug | Group frusemide |
Primary outcome
serum creatinine
Time frame: Change from serum creatinine at 2 weeks
urine volume
Time frame: Change from urine volume at 2 weeks
Serum cystatin-C
Time frame: Change from Serum cystatin-C at 2 weeks
Urine β_2-microglobulin
Time frame: Change from Urine β_2-microglobulin at 2 weeks
3 secondary outcomes
dose of norepinephrine
Time frame: Change from dose of norepinephrine at 2 weeks
blood pressure
Time frame: Change from baseline systolic blood pressure at 2 weeks
central venous pressure
Time frame: Change from central venous pressure at 2 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Dec 2016.
- Background: PubMed 11437769Parker MR, Willatts SM. A pilot study to investigate the effects of an infusion of aminophylline on renal function following major abdominal surgery. Anaesthesia. 2001 Jul;56(7):670-5. doi: 10.1046/j.1365-2044.2001.01374.x.
- Background: PubMed 23055869Lynch BA, Gal P, Ransom JL, Carlos RQ, Dimaguila MA, Smith MS, Wimmer JE Jr, Imm MD. Low-dose aminophylline for the treatment of neonatal non-oliguric renal failure-case series and review of the literature. J Pediatr Pharmacol Ther. 2008 Apr;13(2):80-7. doi: 10.5863/1551-6776-13.2.80.
- Background: PubMed 27500627Yang GZ, Xue FS, Liu GP, Sun C. Use of Aminophylline to Prevent Acute Kidney Injury After Pediatric Cardiac Surgery. Pediatr Crit Care Med. 2016 Aug;17(8):814. doi: 10.1097/PCC.0000000000000838. No abstract available.
- Background: PubMed 24247300Chen HH, Anstrom KJ, Givertz MM, Stevenson LW, Semigran MJ, Goldsmith SR, Bart BA, Bull DA, Stehlik J, LeWinter MM, Konstam MA, Huggins GS, Rouleau JL, O'Meara E, Tang WH, Starling RC, Butler J, Deswal A, Felker GM, O'Connor CM, Bonita RE, Margulies KB, Cappola TP, Ofili EO, Mann DL, Davila-Roman VG, McNulty SE, Borlaug BA, Velazquez EJ, Lee KL, Shah MR, Hernandez AF, Braunwald E, Redfield MM; NHLBI Heart Failure Clinical Research Network. Low-dose dopamine or low-dose nesiritide in acute heart failure with renal dysfunction: the ROSE acute heart failure randomized trial. JAMA. 2013 Dec 18;310(23):2533-43. doi: 10.1001/jama.2013.282190.
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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.
Xuemin Wang, PhD study director
Shanghai 6th People's Hospital
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing aminophylline, frusemide and normal saline in people with Acute Kidney Injury, run by Shanghai Jiao Tong University Affiliated Sixth People's Hospital.
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 4 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 6 Dec 2016. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 Yanding Gao (13917337835, masa_oreo@yeah.net), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
serum creatinine (time frame: Change from serum creatinine at 2 weeks). The study lists 4 primary outcomes in all. 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 NCT02983422, which also lists 4 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 6 Dec 2016.