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

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ClinicalTrials.gov Identifier: NCT02983422
Recruitment Status : Unknown
Verified December 2016 by Gao Yanding, Shanghai Jiao Tong University Affiliated Sixth People's Hospital.
Recruitment status was:  Not yet recruiting
First Posted : December 6, 2016
Last Update Posted : December 6, 2016
Sponsor:
Information provided by (Responsible Party):
Gao Yanding, Shanghai Jiao Tong University Affiliated Sixth People's Hospital

Brief 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.

Condition or disease Intervention/treatment Phase
Acute Kidney Injury Drug: aminophylline Drug: frusemide Drug: normal saline Early Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: Effects of Aminophylline on Renal Function and Urine Volume Acute Kidney Injury Patient
Study Start Date : December 2016
Estimated Primary Completion Date : June 2017
Estimated Study Completion Date : July 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Group 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)
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)

Drug: frusemide
Use frusemide with Syringe pumps,maximum dose to 15mg/h

Placebo Comparator: Group frusemide
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)
Drug: frusemide
Use frusemide with Syringe pumps,maximum dose to 15mg/h

Drug: normal saline
Placebo bolus followed by IV infusions of normal saline (0.9%) every hour (matched by volume and appearance to the treatment group)




Primary Outcome Measures :
  1. serum creatinine [ Time Frame: Change from serum creatinine at 2 weeks ]
  2. urine volume [ Time Frame: Change from urine volume at 2 weeks ]
  3. Serum cystatin-C [ Time Frame: Change from Serum cystatin-C at 2 weeks ]
  4. Urine β_2-microglobulin [ Time Frame: Change from Urine β_2-microglobulin at 2 weeks ]

Secondary Outcome Measures :
  1. dose of norepinephrine [ Time Frame: Change from dose of norepinephrine at 2 weeks ]
  2. blood pressure [ Time Frame: Change from baseline systolic blood pressure at 2 weeks ]
  3. central venous pressure [ Time Frame: Change from central venous pressure at 2 weeks ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02983422


Contacts
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Contact: Yanding Gao 13917337835 masa_oreo@yeah.net
Contact: Haiyan Wang 18930174845 mgul@163.com

Sponsors and Collaborators
Shanghai Jiao Tong University Affiliated Sixth People's Hospital
Investigators
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Study Director: Xuemin Wang, PhD Shanghai 6th People's Hospital
Publications:
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Responsible Party: Gao Yanding, Deputy chief physician, Shanghai Jiao Tong University Affiliated Sixth People's Hospital
ClinicalTrials.gov Identifier: NCT02983422    
Other Study ID Numbers: SSH-ICU-017
First Posted: December 6, 2016    Key Record Dates
Last Update Posted: December 6, 2016
Last Verified: December 2016
Additional relevant MeSH terms:
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Acute Kidney Injury
Renal Insufficiency
Kidney Diseases
Urologic Diseases
Aminophylline
Furosemide
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Cardiotonic Agents
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Purinergic P1 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Protective Agents
Diuretics
Natriuretic Agents
Sodium Potassium Chloride Symporter Inhibitors
Membrane Transport Modulators