Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03068104 |
| Other study ID # |
ruut-seger-201702262039 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
January 2017 |
| Est. completion date |
December 31, 2018 |
Study information
| Verified date |
February 2020 |
| Source |
Karolinska Institutet |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
This study aims to estimate the difference between predicted and provided massive transfusion
in adult trauma patients admitted to university hospitals in urban India.
Description:
Background
Trauma fatalities account for 9 % of the world's deaths, superseding the number of deaths
caused by HIV/AIDS, tuberculosis and malaria combined, disproportionately affecting low- and
middle-income countries (LMIC). Hemorrhage is one of the leading causes of preventable death
among trauma patients. Up to 5 % of trauma patients require massive transfusions (MT),
defined as administration of ten or more units of packed red blood cells (PRBC) within 24
hours of injury.
India is an LMIC lacking structured trauma care systems and where blood products remain a
scarce commodity. There is a sizeable gap in supply and demand as India lacks about four
million units of blood per year according to World Health Organization estimates. The
in-hospital mortality in an urban Indian trauma setting has been found to be twice that of
high-income equivalents and inadequate resuscitation and bleeding control of hemorrhaging
patients has been found to be the main cause of preventable deaths.
Considering the general lack of blood components in India it is reasonable to assume that
there is an unmet need of blood transfusions in trauma patients as well. The extent of the
potentially unmet need of MT constitutes a major gap of knowledge and also an important basis
for resource allocation and development of MT protocols suited for local needs, hence our
research question: what is the difference between predicted need for MT and actual
transfusion in an urban Indian trauma setting?
Aim
To estimate the difference between predicted need for MT and provided MT in adult trauma
patients in an urban Indian setting. The hypothesis is that there will be a substantial
discrepancy between predicted need and provided MT, indicating an unmet need of blood
transfusions.
Study design
A retrospective analysis of the Towards Improved Trauma Outcomes in India (TITCO) cohort will
be conducted.
Setting
The TITCO dataset includes 16,047 patients enrolled between July 2013 and December 2015 from
four public university hospitals, namely the King Edward Memorial Hospital and Lokmanya Tilak
Municipal General Hospital in Mumbai, Jai Prakash Narayan Apex Trauma Center in New Delhi and
the Seth Sukhlal Karnani Memorial Hospital in Kolkata. These hospitals are characterized by
nominal patient fees and all operate trauma units.
An externally employed and trained data collector working eight-hour shifts in each facility
gathered patient data in a prospective observational fashion, rotating between day, evening
and night shifts. Data from patients admitted outside of these hours was retrieved
retrospectively within days of admission. The patients were followed until discharge or
death, whichever occurred first.
Source and method of participant selection
Participants were selected consecutively during the study period according to the
aforementioned eligibility criteria, either via direct observation during the data
collector's shift or through retrospective data retrieval from patient records.
Covariates
To estimate the proportion of patients predicted to need MT the Assessment of Blood
Consumption (ABC) score will be used. The rationale for using the ABC score in this context
is that it is based on routinely recorded vital signs and examination results that are all
available in TITCO, unlike other scores that also require laboratory results. Further, the
intent is not to validate the score, but to use it as an informed basis for identifying
patients with substantial bleeding. ABC is based on four dichotomous non-laboratory
parameters that are readily available in the early assessment phase.
Penetrating mechanism (0=no, 1=yes)
Arrival Systolic Blood Pressure <= 90 mm Hg (0=no, 1=yes)
Arrival Heart Rate >= 120 bpm (0=no, 1=yes)
Positive focused assessment sonography for trauma (FAST) (0=no, 1=yes)
A score of two or more has been set to indicate need for MT. Age, sex, and mechanism of
injury in addition to the variables included in the ABC score will be presented to
characterize the study sample.
Data sources/measurement
Where FAST recording in the study sample is not reported as "positive" relevant free text
terms will be used to find indications of free fluid in abdomen, pelvis or pericardium. Where
FAST recording is missing relevant ICD-10 codes will be used for screening the free text
variables reporting computer tomography (CT) and intraoperative findings.
The proportion of patients predicted to need MT (a) will be estimated by dividing the number
of patients with an ABC score of two or more by the total number of patients in the study
sample. The proportion of actual MT received (b) will then be calculated by dividing the
number of patients who received ten or more units of PRBC with the total number of patients
with complete clinical data.
Bias
The data collectors were externally trained and funded by project management. The data was
obtained through direct observation and retrieval from patient records without interference
in clinical work. All data collectors had at least a health science master's degree and were
continuously trained and supervised by project management. The collected data is
multi-institutional, likely reducing the effects of highly operator and setting dependent
variables.
Injury severity bias due to missing data from severely injured patients is a recognized
problem in trauma registries and to counteract this it is imperative to account for as many
patients as possible using alternatives for the FAST positive variable that would indicate
ongoing intra-abdominal, pericardial or pelvic hemorrhage. However, the approach of using
surrogates for FAST may also yield misleading results due to overestimation. To estimate the
magnitude of this source of bias a sensitivity analysis will be conducted.
In addition, the ABC score was originally developed and validated in a high-income setting
with a likelihood of differing demography and patterns of injury mechanism, possibly yielding
results not representable of true MT needs in our study population. However, in this case the
ABC score will rather be used as a tool for the estimation of blood needs rather than as a
prediction tool or aid in clinical decision-making.
Study size
Based on previous research it is assumed that 10% of patients will be predicted to need MT.
In contrast, based on clinical experience from the study setting, it is assumed that a
maximum of 5% received it. Assuming that 10 % (~ 1600 patients) will be predicted to need an
MT and 5 % (~ 800 patients) received it then the sample size based on a two-sided paired
comparison of proportions, i.e. two-sided McNemar's test, needed to detect this difference
with 80% power is 369 patients, setting alpha to 5% and beta to 20%. In other words, because
all complete observations in the cohort will be analyzed, it can safely be said that this
study is powered to detect this difference at the 80% level.
Quantitative variables
When characterizing the study sample, all quantitative variables will be presented as
continuous. In the calculation of the ABC score the quantitative variables arrival heart rate
and arrival systolic blood pressure will be dichotomized as detailed in the covariate section
above.
Statistical methods
All statistical analyses will be performed in R, a free open-source software for statistical
computing and graphics. Qualitative sample characteristics will be presented using number and
percentage whereas quantitative sample characteristics will be presented as median, values at
the 25th and 75th percentile, as well as minimum and maximum values.
The main analysis is a complete case analysis where observations with missing covariate
values will be excluded. Depending on the amount of missingness, multiple imputation using
chained equations might be used to handle missing data. The main analysis will thereafter be
conducted in two steps. First, the proportion of patients with an ABC score ≥ 2, i.e.
patients with predicted need of MT will be calculated. Thereafter the proportion of patients
who actually received MT (b) will be calculated based on transfusion data in the TITCO
registry. The outcome is defined as the difference between the proportion of adult patients
predicted to receive MT and the proportion of patients who did receive MT.
Sensitivity analyses
Based on clinical experience in this particular setting a sensitivity analysis will be
conducted with a cutoff value of 4 units of PRBCs in 24 hours for the definition of MT. A
sensitivity analysis will also be conducted by restricting the analysis to FAST positive
patients where coding using CT or intraoperative findings was not used.
