Glycemic Control and Surgical Site Infection Incidence Among Liver Transplantation Recipients

March 24, 2020 updated by: Ramon Oliveira

Postoperative Glycemic Control and the Surgical Site Infection Incidence Among Liver Transplantation Recipients: Randomized Clinical Trial

Context: The hyperglycemia is an important independent risk factor for the Surgical Site Infection (SSI) development among liver transplantation recipients. Objective: To evaluate the effects of an intensive postoperative protocol of blood glucose management on the surgical site infection incidence among liver transplantation recipients. Material and methods: It is an open-label clinical trial that will be randomized into 2 groups of blood glucose (BG) control: patients will undergo BG control regular in the facility chosen to research development (BG targeted 130-180 mg/dL) and the second one will undergo intensive BG control (BG targeted 80 - 130 mg/dL) until patients are eating at least 50% of a full liquid diet or receiving bolus tube feedings. A computer program will be employed to generate the randomized schedule that will be put into sequentially numbered opaque sealed envelopes by an external expert to research. A finger prick device will be used to measure the blood glucose. A blinded adjudication committee to analyse the primary endpoint SSI will adopt the SSI criteria given by the Centers for Disease Control and Prevention. The research proposal will be registered on ClinicalTrials.gov database. Central tendency and dispersion measures, Pearson's χ2 test, Fisher's Exact Test, Mann-Whitney, Wilcoxon-Mann-Whitney and survival analysis by Kaplan-Meier estimated and Log-rank test will be used for data analyses. Expected outcomes: The results of the study should contribute to establishing better clinical practices on glycemic control in the liver transplantation recipient's postoperative period aiming to reduce SSI incidence and its associated morbidity and mortality.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The Surgical Site Infections (SSI's) are the most frequent healthcare-associated infections and are an important infectious complication in the postoperative period among liver transplantation (LT) recipients. SSI incidence among LT recipients, whose allografts were from deceased donors, varied from 9.6% to 35.5% according to a recent literature review. In general surgical procedures, SSI increases the length of stay, morbidity and healthcare costs. Besides that, among LT recipients SSI can raise the risks of the allografts dysfunctions, acute rejections and as a consequence a reduction in the recipient's survival.

There are several risk factors for SSI among LT recipients. There is a relationship among supply sterilization quality, the characteristics of surgical procedure, the operation room environment as well as the allograft's and recipient's conditions and SSI occurrence. In regard to LT recipients, results from previous research highlighted hyperglycemia as an important independent predictor of SSI. Furthermore, regarding this population, it is known from observational studies that LT recipients affected by hyperglycemia are exposed, approximately, to three times the risk of SSI comparatively to LT recipients not exposed.

The concern about maintaining normoglycaemia in acute care facilities is not recent; several studies have been done including on clinical and surgical patients from some medical specialities showing the morbidity and mortality reduction throughout the adoption of strict glycaemic control protocols.

However, among critical surgical patients the LT recipients are highlighted; since they are exposed to impairment in blood glucose metabolism in the perioperative period as a consequence of an intraoperative acute stress state, blood loss and transfusions, the reperfusion phase, use of glucocorticoids and catecholamines.

Results from previous studies pointed the hyperglycaemia among LT recipient as a frequent complication, 94% of them presented it at least once in the transplantation's postoperative period.

The high blood glucose levels can produce electrolyte and acid-base disturbances besides altered plasmatic distribution of sodium. There are impairments to the white blood cells activities, such as reduction in the adherence, chemotaxis, phagocytosis and superoxide formation. Lymphocytes apoptosis combined with T-cell activities suppression besides attenuation of immunoglobulin's work as a consequence of glycosylation.

In spite of evidence from laboratory studies that indicate remarkable impairments caused by hyperglycemia in immune model animals immunologic system, uncertainties remain to evaluate the glycaemic control as a strategy for SSI prevention. Analysing the guidelines to prevent SSI published by World Health Organization, Centers for Disease Control and Prevention (United States of America), National Institute for Health and Care Excellence (United Kingdom), Society for Healthcare Epidemiology of America (United States of America) and Brazilian Health Regulatory Agency conditional recommendation regard the adoption of strategies to strict glycaemic control in the postoperative phase, besides there is no consensus about how glycaemic level could work as a protective factor for SSI among patients who underwent general surgeries.

Moreover, there have been few investigations evaluating the hyperglycaemia effects or blood glucose control in the postoperative phase of LT recipients. Besides the few studies concerned on the topic among LT recipients, the majority of them were observational studies, designed as retrospective cohorts, which could compromise the body's evidence quality. Also, in the previous studies enrolled patients underwent liver-kidney transplantation, which can cause a negative impact on the effects of glycemic control analyses and there is research where recipients presented lower means of Model for End-Stage Liver Disease (MELD) from 19.0 to 28.2 that are lower MELD means than the observed in Brazilian transplantation centres. Finally, we observed the absence of clear criteria for SSI diagnosis in some studies.

It is known that the preoperative screening in living donor LT of donors and recipients as baseline characteristics are different of LT whose allografts came from deceased donors; for instance, liver-kidney recipients who undergo to distinct immunosuppression schemes. Furthermore, lower MELD scores represent LT recipients that could be exposed to diverse risk factors for SSI when compared to LT recipients who the MELD score is higher.

Thus, it sounds appropriate that research aiming to evaluate the effect of strict blood glucose control on SSI incidence among LT recipients should be made. In addition, nurse-initiated blood glucose control protocols, among critically ill patients, are frequently developed. And, a recent literature review pointed to the lack of prospective studies that addressed the evaluation of the outcomes of strict glycaemic control among LT recipients on SSI incidence.

The study hypothesis is: the postoperative strict glycaemic control reduces the SSI incidence among LT recipients.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
41

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
    • São Paulo
      • São José Dos Campos, São Paulo, Brazil, 12210110
        • Hospital Santa Casa de São José dos Campos

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Recipients of LT whose allograft came from deceased donors
  • Able to give informed consent personally or via a family member who has appropriate authorization to do so if patient unconscious.
  • Blood glucose level over 130 mg/dL in the first 24 hours postoperatively

Exclusion Criteria:

  • The patients that underwent any kind of surgery with or without prosthesis implant in the 30 days before the LT
  • Recipients submitted to multiple organ transplantation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Strict Glycemic Control Group
Intravenous insulin as described by Keegan and Cols. 2010.
Procedure: Strict Glycemic Control Group
The strict protocol adopted to conduct the study was proposed by Keegan e Cols.(2010) to be used among adult LT recipients that consist of a continuous intravenous insulin infusion. The targeted blood glucose range is 80-130 mg/dL. The procedure must be stopped when the patient can ingest at least 50% of liquid diet or receive bolus tube feedings.
Active Comparator: Standard Glycemic Control Group
Subcutaneous insulin as instititional protocol.
Procedure: Standard Glycemic Control Group

The targeted blood glucose range is 130-180 mg/dL

  • Blood glucose reading: ≤ 180 mg/dL - subcutaneous insulin dose: 0
  • Blood glucose reading: ≥181 mg/dL and ≤250 mg/dL - subcutaneous insulin dose: 5 IU
  • Blood glucose reading: ≥251 mg/dL and ≤300 mg/dL - subcutaneous insulin dose: 10 IU
  • Blood glucose reading: ≥301 - subcutaneous insulin dose: 15 IU

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Surgical Site Infection
Time Frame: SSI occurs within 30 days after the LT
Surgical site infection following the Centers for Disease Control and Prevention defining criteria (2018)
SSI occurs within 30 days after the LT

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Hyperglycemia
Time Frame: During first 48h ICU stay
Hyperglycemia > 250 mg/dL
During first 48h ICU stay
Hypoglycemia
Time Frame: During first 48h ICU stay
Hypoglycemia < 60 mg/dL
During first 48h ICU stay
Duration of mechanical ventilation
Time Frame: Within 30 days after LT
Duration of mechanical ventilation through postoperative ICU stay
Within 30 days after LT
ICU stay
Time Frame: Within 30 days after LT
ICU stay until 30 days after LT
Within 30 days after LT
Ward stay
Time Frame: Within 30 days after LT
Postoperative ward stay
Within 30 days after LT
Death
Time Frame: 90 days after LT
Death within 90 days after LT
90 days after LT
Surgical Site Infection or death
Time Frame: Surgical site infection within 20 days following liver transplantation or death within 90 days following liver transplantation
Surgical site infection following the Centers for Disease Control and Prevention defining criteria (2018)
Surgical site infection within 20 days following liver transplantation or death within 90 days following liver transplantation
Hospital length of stay
Time Frame: Until 100 weeks after liver transplantation
Time between the hospital admission to liver transplantation and hospital discharge
Until 100 weeks after liver transplantation

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
PPI preoperative use and SSI
Time Frame: Preoperative period
Proton-pump inhibitor and ocurrence of SSI
Preoperative period

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Ramon Oliveira

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Vanessa B Poveda, Ph.D
  • Study Director: Judith Tanner, Ph.D
  • Study Director: Jorge M Padilla, M.Sc

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 11, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 25, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 15, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 2, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 14, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 22, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 26, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 24, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 80351717.7.0000.5392
  • U1111-1210-2322 (Other Identifier: Universal Trial Number - World Health Organization)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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