Effects of Aminophylline on Renal Function and Urine Volume of AKI Patient

Acute Kidney Injury Clinical Trial

Official title:

Effects of Aminophylline on Renal Function and Urine Volume Acute Kidney Injury Patient

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02983422
• Other study ID #: SSH-ICU-017
• Status: Not yet recruiting
• Phase: Phase 0
• First received: November 26, 2016
• Last updated: December 2, 2016
• Start date: December 2016
• Est. completion date: July 2017

Study information

• Verified date: December 2016
• Source: Shanghai Jiao Tong University Affiliated Sixth People’s Hospital
• Contact: Yanding Gao
• Phone: 13917337835
• Email: masa_oreo[@]yeah.net
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: July 2017
• Est. primary completion date: June 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients with acute injury (AKI) with no lack of circulating volume (central venous pressure >8cmH2O)

Exclusion Criteria:

• 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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Kidney Injury

Intervention

Drug:
• aminophylline
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)
• frusemide
Use frusemide with Syringe pumps,maximum dose to 15mg/h
• normal saline
Placebo bolus followed by IV infusions of normal saline (0.9%) every hour (matched by volume and appearance to the treatment group)

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Jiao Tong University Affiliated Sixth People’s Hospital

References & Publications (4)

Chen 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, Dávila-Román 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. — View Citation

Lynch 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. — View Citation

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. — View Citation

Yang 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	serum creatinine		Change from serum creatinine at 2 weeks	No
Primary	urine volume		Change from urine volume at 2 weeks	No
Primary	Serum cystatin-C		Change from Serum cystatin-C at 2 weeks	No
Primary	Urine ß_2-microglobulin		Change from Urine ß_2-microglobulin at 2 weeks	No
Secondary	dose of norepinephrine		Change from dose of norepinephrine at 2 weeks	No
Secondary	blood pressure		Change from baseline systolic blood pressure at 2 weeks	No
Secondary	central venous pressure		Change from central venous pressure at 2 weeks	No