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Lithium in Acute Kidney Injury (LSCAKI)

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ClinicalTrials.gov Identifier: NCT03056248
Recruitment Status : Not yet recruiting
First Posted : February 17, 2017
Last Update Posted : February 17, 2017
Sponsor:
Information provided by (Responsible Party):
Sairah Sharif, Lifespan

Brief Summary:
A growing body of pre-clinical evidence suggests that glycogen synthase kinase 3β (GSKβ) is implicated in the development and progression of acute kidney injury (AKI). Lithium is a naturally occurring standard inhibitor of GSKβ. The purpose of this study is to examined if low dose lithium carbonate is able to reduce the incidence of AKI in patients undergoing cardiac surgery who are placed on cardiopulmonary bypass during surgery. We hypothesize that low dose lithium might reduce the incidence and duration of AKI in patients undergoing cardiac surgery who are on cardiopulmonary bypass.

Condition or disease Intervention/treatment Phase
Acute Kidney Injury Drug: Placebo oral capsule Drug: Lithium Carbonate Phase 4

Detailed Description:

Cardiac surgery associated acute kidney injury (CSA-AKI) is a significant problem. The prevalence varies from 0.3% to 22.9% depending on the definition of AKI. The pathogenesis of AKI in this population is multifactorial. Factors associated with AKI in such patients include increased age, preoperative elevated creatinine, presence of diabetes, reduced ejection fraction, increased body weight, and presence of carotid artery bruit, duration of cardiopulmonary bypass, aortic cross clamp time, and duration of surgery. CSA-AKI is an independent predictor of mortality, morbidity, increased length of stay and hospitalization costs. Moreover these patients are also at increased risk of chronic kidney disease and end stage renal failure in the future.

Various pharmacologic approaches that have been tried to prevent early CSA-AKI such as diuretics, vasodilators, and anti-inflammatory drugs. Fenoldopam, atrial natriuretic peptide, and brain natriuretic peptide have shown little renoprotection. However these strategies lack high quality evidence to support their use and are not standard of care. There is no strong evidence to suggest any single or multiple pharmacotherapy that significantly impacts in reducing CAS-AKI. Thus the current best therapy for CSA-AKI is prevention, supportive care, hemodynamic optimization and renal replacement therapy.

AKI is an extremely complex process involving multiple pathophysiologic pathways. Glycogen synthase kinase 3β (GSK3β) is implicated in many pathways beyond glycogen metabolism and has been shown to be an important player in the development of AKI . Lithium is a US Food and Drug Administration (FDA)-approved drug which has been used for over 50 years as first line agent to treat mood disorders. It is a standard inhibitor for GSK3β. Latest evidence in murine models of cisplatin-induced AKI and ischemia/reperfusion-induced AKI suggests that lithium treatment may attenuated kidney dysfunction and kidney histologic injury following AKI. Lithium was able to promote kidney tubular cell repair hence improvement of AKI in murine models. In addition, lithium has also been found to exert an anti-proteinuric and renal reparative effect. On this background we want to explore the potential preventive and therapeutic role of lithium carbonate in CSA- AKI.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Patients will be randomized to lithium versus placebo and rates of acute kidney injury will be measured
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: Patients and investigators will be blinded to the study
Primary Purpose: Prevention
Official Title: Lithium in Cardiac Surgery Related Acute Kidney Injury: A Pilot Study
Estimated Study Start Date : April 1, 2017
Estimated Primary Completion Date : December 30, 2017
Estimated Study Completion Date : January 1, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Lithium
Patients will be identified by chart review and be explained the purpose of the study and informed consent taken
Drug: Lithium Carbonate
On day 0, the day of the cardiac surgery oral lithium will be given at dose 900mg once On day 1, one day after cardiac surgery oral lithium will be given at dose 900mg once On day 2, two days after cardiac surgery oral lithium will be given 900mg once
Other Name: Lithium

Placebo Comparator: Placebo
Patients will be identified by chart review and be explained the purpose of the study and informed consent taken
Drug: Placebo oral capsule
On day 0, the day of the cardiac surgery placebo will be given once On day 1, one day after cardiac surgery placebo will be given once On day 2, two days after cardiac surgery placebo will be given once
Other Name: Placebo




Primary Outcome Measures :
  1. Change in serum creatinine mg/dl [ Time Frame: 1 month ]
    Renal function


Secondary Outcome Measures :
  1. Peak creatinine mg/dl [ Time Frame: 1 month ]
    Renal function

  2. Neutrophil gelatinase-associated lipocalcin (NGAL) ng/ml [ Time Frame: 3 days ]
    Renal function

  3. Kidney injury molecule-1 (KIM1) ng/ml [ Time Frame: 3 days ]
    Renal function



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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:

  • A male or female greater than 18 years
  • Stable renal function with creatinine change <0.3mg/dl in the preceding 1 month prior to scheduled surgery
  • Procedure such as aortic valve surgery, mitral valve surgery, coronary artery bypass grafting, or combination of the above mentioned procedures
  • Have estimated glomerular filtration rate greater than or equal to 15ml/min/ 1.73m2 as calculated by chronic kidney disease Epidemiology Collaboration (CKD-EPI) formula

Exclusion Criteria:

Subjects who:

  • Are taking lithium prior to surgery for any reason
  • Have ejection fraction of <30% prior to surgery
  • Have estimated glomerular filtration rate <15ml/min/ 1.73m2 as calculated by chronic kidney disease Epidemiology Collaboration (CKD-EPI) formula
  • Having cardiac surgery to be performed without using cardiopulmonary bypass
  • Has ongoing sepsis or history of sepsis in the last 2 weeks, defined as having 2 of the following criteria T >38C or <36C, pulse rate >90/min, RR >20/min, WBC >12 or >10% polymorphonuclear cells plus a documented source
  • Has documented rise in creatinine ≥ 0.3mg/dl in the preceding one month prior to surgery

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): NCT03056248


Contacts

Sponsors and Collaborators
Lifespan

Publications of Results:
Responsible Party: Sairah Sharif, Assistant Professor, Lifespan
ClinicalTrials.gov Identifier: NCT03056248     History of Changes
Other Study ID Numbers: 02116
First Posted: February 17, 2017    Key Record Dates
Last Update Posted: February 17, 2017
Last Verified: February 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Wounds and Injuries
Acute Kidney Injury
Renal Insufficiency
Kidney Diseases
Urologic Diseases
Lithium Carbonate
Antidepressive Agents
Psychotropic Drugs
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs