Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02999386 |
| Other study ID # |
14471/14 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
October 2016 |
| Est. completion date |
December 2019 |
Study information
| Verified date |
July 2020 |
| Source |
Hamad Medical Corporation |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The clinical relevance of the observed stress induced hyperglycemia in trauma patients
remains unclear. The earlier studies suggested the implications of cytokines in stress
induced hyperglycemia and the outcomes after trauma. To date, there is little information
available regarding the effect of diabetic hyperglycemia (occult or known) on outcomes after
trauma and whether these patients represent a distinct group with differential outcomes when
compared to those with stress-induced hyperglycemia. Herein, the purpose of this study is to
identify the incidence of stress induced hyperglycemia as well as diabetic hyperglycemia in
trauma patients and to investigate the association between proinflammatory cytokine levels
and hyperglycemia in our trauma population.
Description:
Intensive glucose control is vital for prognosis and preservation of normal physiologic
status in trauma patients. The acute effects of severe trauma, infection, and surgery result
in remarkable metabolic stress on the human body. Hyperglycemia is a normal metabolic
response to stress and injury [1]. Irrespective of the involved injury mechanism,
post-traumatic metabolic changes occur due to stress in terms of an increased glucose
production, decreased insulin production, and insulin resistance in the peripheral tissues
and eventually lead to a state of hyperglycemia. Traumatic injury also induces changes in
endogenous hormone production and enhanced utilization of metabolites that usually lead to
stress related hyperglycemia. Measurement of HbA1c levels can be used as a screening tool to
discriminate unknown diabetes mellitus from stress-induced hyperglycemia (SIH). Published
studies that have evaluated the association between presenting hyperglycemia and worse
outcomes in trauma patients have all consistently showed higher mortality and infection rates
in patients presented with elevated serum glucose levels of 200 mg/dL or more [2-5]. A recent
study evaluated the differential effect of SIH in comparison to diabetic hyperglycemia (DH)
on outcomes in trauma victims. The authors observed that as opposed to DH, SIH is associated
with a higher mortality rate after injury [4]. A prospective study of patients with severe
traumatic brain injury demonstrated that admission glucose levels >11.1 mmol/L were
associated with increased mortality and poor neurologic outcomes [6]. Stress associated with
critical illness is characterized by the activation of inflammatory cellular mediators [7].
During acute illness there is an increase in the systemic inflammatory response that is
characterized by increased production of pro-inflammatory cytokines. Importantly, there is
relationship between abnormal cytokine production and hyperglycemia in severe sepsis patients
which aggravates the immune response leading to poor clinical outcomes. Recent studies
suggested that interleukin-6 (IL-6) is involved in glucose metabolism and insulin action. The
proinflammatory IL-6 is normally released upon infection; however, it induces insulin
resistance during conditions of hyperglycemia [8]. Moreover, IL-18 levels are significantly
elevated in diabetic patients with microalbuminuria as compared with patients with
normoalbuminuria [9]. This might indicate that certain interleukins (IL) are involved in the
pathogenesis of SIH. Though, the clinical relevance of the observed SIH in trauma patients
remains unclear. The earlier studies suggested the implications of cytokines in SIH and
outcomes after trauma. To date, there is little information regarding the effect of diabetic
hyperglycemia (occult or known) on the clinical outcomes after trauma and whether these
patients represent a distinct group with differential outcomes when compared to those with
SIH. The purpose of this study is to identify the incidence of SIH as well as diabetic
hyperglycemia in trauma patients and to investigate the association between the
proinflammatory cytokine levels and hyperglycemia in trauma population.
Primary objective:
- To evaluate the outcomes of stress induced hyperglycemia in patients presented with
traumatic injury.
Secondary objectives:
- To investigate the association between pro-inflammatory cytokine levels and SIH in
trauma patients.
- To identify the incidence of SIH and occult diabetes mellitus in trauma population.
It is a prospective study which will include all adult trauma patients who require hospital
admission and have been investigated for random plasma glucose level and HbA1C measured
within 5 hours of admission. All trauma patients will undergo thorough clinical assessment
and resuscitation according to the Advanced Trauma Life Support (ATLS) guidelines. The
present study will screen all traumatic injury patients presented to the trauma room and
those who are willing to participate and provide written informed consent or consented by the
relatives or used emergency consent (Exception from Informed Consent Requirements for
Emergency Research" Policy # 11026) to draw blood for the investigations will be included in
the study. All the study subjects will be managed according to the standard care of the
hospital. The investigators will directly access all adult traumatic injury patients that
will be presented to the trauma room and review the medical file and/or electronic medical
record (EMR) to confirm the eligibility. Usually trauma patients are unconscious, under shock
and are physically and mentally unfit to communicate or sign consent. The trauma surgeon will
explain the consent form to the legal representatives of the subjects in a separate chamber
in the ICU or in private room in the clinic.
Consent and recruitment procedures will be done in such a way that it will not be disclosed
to other patients in the trauma room or in the ward. The information regarding patient's
enrollment will be kept confidential and all study related interactions with the
subject/patient's legal representative will be done in isolated room in the wards or in the
clinics to maintain complete privacy. To safeguards the severe trauma patients, informed
consent will be taken to participate in research by a legally authorized representative on
behalf of a cognitively impaired subject. In absence of any legally authorized
representative, the investigators will use emergency consent (Exception from Informed Consent
Requirements for Emergency Research" Policy # 11026).
Patients who partially recover cognition will be asked to provide Assent and those fully
recovered their cognition to understand the study will be asked for informed consent to
continue participation. For trauma patients who are unconscious, under severe shock and are
physically and mentally unfit to communicate, legally authorized representative will be
identified with the help of patient's attendants. Explaining the consent will take around
half an hour, and if the legal representative consented to allow subject participation within
5 hours of admission, he/she will be enrolled. Since the research investigations needs to be
done during early hours of admission waiting time could be maximum 2-3 hours post admission.
This study did not include any specific procedure which could provide distress to the
participants. And the subject's privacy will be specifically taken care.
Sample size estimation: There is lack of information on the incidence of stress-induced
hyperglycemia among trauma patients in Qatar. However, the current literature reported the
incidence of stress-induced hyperglycemia (≥200 mg/dl) in trauma patients ranges from 10%-17%
for all trauma admissions [3,4]. Therefore, taking the frequency of hyperglycemia to be 15%
with 5% confidence limit and 97% confidence level, a total of 250 consecutive trauma patients
needs to be included in the study. The investigators aim to complete the target of subject
recruitment within 12 months and this research may take 18 months to be completed.
Bio-specimens: The blood specimen for research (10 ml initially after recruitment and 5 ml
after 24 and 48 hours of admission) will be drawn together with the routine blood
investigation.
For each study participant, blood will be drawn on admission to investigate Hemoglobin,
HbA1C, blood glucose levels, Lactate, Base Deficit, High sensitive troponin T (HsTnT),
Interleukin-6, Interleukin-18 and high sensitive C-reactive protein. Moreover, after 24 and
48 hours of admission, fasting blood glucose levels, hemoglobin, Lactate, Base Deficit,
Interleukin-6, Interleukin-18 and high sensitive C-reactive protein will be repeated for all
the patients. The main exposure will be hyperglycemia, defined as serum glucose 200 mg/dL or
more. This level of glucose has previously been used by several trauma studies, and it is a
commonly utilized cutoff to define hyperglycemia. Diabetes mellitus will be determined by
patient history and/or admission HbA1c ≥ 6.5%. This level of HbA1c is based on current
recommendations for the diagnosis of diabetes mellitus from the American Diabetes Association
[10]. All the study participants will be managed according to the standard care of the
hospital.
The investigators expect to enroll 250 consecutive trauma patients to be included in the
study from the Hamad General Hospital, Doha, Qatar (this number of participants will be per
center in case it becomes multicenter study to reach 750-1000 in total). The subject will be
in the research until discharge from the hospital or died in the hospital and there will be
no follow-up visits for the research.
Data collection & integrity: For each study participant, information will be collected
regarding demographics (e.g., age, sex, nationality), injury (i.e., injury mechanism, ISS),
and clinical characteristics (i.e., hospital stay, ICU days, and days on ventilator support).
Information will be collected regarding outcomes, including mortality and in-hospital
complications (i.e., pneumonia, renal failure, sepsis, Acute Respiratory Distress Syndrome
and multiorgan failure).
The principal investigator (PI) will provide specific pre-assigned numbers to each sample
collected and only the PI will know the subject identifier and all others will work with the
number only. However, in the process of receiving and storage of samples, one appointed
technical staff of laboratory services can have the access to the blood specimens. The
investigator will track all the specimens received by allotting unique subject identifier for
all blood specimens and track the sample transportation, processing, and consumption. Each
sample will be labeled properly in color-coded cryo boxes at -80°C and will be discarded
immediately after the test. Only the PI will have the access to the data which has been coded
with subject identifier. The de-identified data from the individual data collection sheet
will be entered by the research coordinator into the password protected Excel file.
Participation in this study is voluntary and the participant can be discontinued at any time,
if he/she is willing to withdraw. If the participant is interested to withdraw from the
study, he/she needs to contact the lead principle investigators of the study and this
decision will not affect their medical care. In case of subjects recruited by emergency
consent, after patient recovery he/she will have the right to withdraw from the study at any
time voluntarily. If the patient chooses to withdraw from the study, they will be asked for
permission to use their data up to the time of withdrawal. Data will be collected up to the
time of withdrawal. Data will be collected up to the time of withdrawal. The existing data
will not be removed from research and will be used for intention-to-treat analysis. However,
the specimens will be discarded and no further data will be generated.
Data management: Data collection sheet will be used to record all relevant information of
individual subjects. The de-identified data from the individual data collection sheet will be
entered by the research coordinator into the password protected Excel file. Only the PI will
have the access to the data which has been coded with subject identifier. The PI designated
research team member will have the access to the de-identified data. Data will be stored and
secured at logbook/secured computer with the PI. Hard copies will also be stored in closed
envelopes in locked cabinets in PI's office. The data will be kept for a period of five years
and then later will be destroyed. Data will be stored by the Hamad Trauma Center (HTC) Lead
PI from all the participating centers and no data will be transferred from HTC to other
centers. This study is opened for collaborative centers to be a multicenter study.
