Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02259270 |
| Other study ID # |
S55785 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
September 30, 2014 |
| Last updated |
May 2, 2017 |
| Start date |
August 2014 |
| Est. completion date |
July 2016 |
Study information
| Verified date |
August 2014 |
| Source |
Universitaire Ziekenhuizen Leuven |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Acid suppressive therapy (AST) is used in a variety of indications in prevention and
treatment of gastric acid related disorders. In recent years, an increase in the use of acid
suppressive therapy has been documented. It has generally been accepted that these agents
are effective and safe. However, very recently, reports describing hypomagnesaemia,
hypocalcemia, vitamin B12 deficiency and enteric infections, were published.
The goal of this study is to evaluate 1) how many cases of long-term ambulatory treatment
with AST are initiated during hospital stay (= ASTRA-1), and 2) assess the appropriateness
of initiation of AST and the appropriateness of continuation of AST at discharge in a subset
of the hospitalized patient population (= ASTRA-2). Finally, the pharmacoeconomic impact of
inappropriate AST during hospitalisation will be calculated from these data.
The primary endpoint is defined as the number of patients on long-term ambulatory AST after
initiation in the hospital. Secondary endpoints are the appropriateness check of AST both at
the level of initiation during hospitalization and at discharge (appropriate continuation);
also the impact on the hospital budget (lump sum budget) will be calculated, and potential
cost avoidance for long-term ambulatory inappropriate AST will be estimated from a
healthcare payer perspective for a period of 1, 3, 6 and 12 months.
Description:
ASTRA 1
A retrospective, multi-centric, observational study will be carried out in 9 Belgian
hospitals. Patients will be recruited hospital wide in all participating hospitals.
All hospitalized adult patients (defined as 18 years or older at the moment of discharge)
discharged from participating hospitals from in 01-07-2012 until 01-07-2013 will be
included, if they were treated at any moment during hospitalization with AST (both H2A,
defined as all drugs belonging to ATC A02BA, and PPI, defined as all drugs belonging to ATC
A02BC). Younger patients are excluded as they are often treated with compounded suspensions
and these preparations are impossible to match with the dispensed medication. Fulfillment of
these criteria will be based on queries retrieving data from the hospital information
system. The query will generate, for each participating hospital, a list of unique
hospitalizations. In order to guaranty the patients privacy, datasets will be made anonymous
by a trusted third party (see further in protocol). Reporting will be anonymous, never on an
individual patient, physician or hospital.
For this list, all potentially interesting covariates will be documented by adding coded
patient-related data, in order to allow determination of associated risk factors by uni- and
multivariate analysis. The following patient-related information will be requested from the
HIS: number of participating hospital, date of admission and discharge, age, weight, sex,
region of living, length of stay, diagnosis on admission, hospital outcome in terms of
mortality, comorbidity details (based on ICD-9 coding), presence of gastro(duodenal)
investigations during hospital stay (eg. gastroscopy), discipline of treating clinician
and/or hospital ward.
Patients with multiple hospitalizations during the inclusion period will be included. Each
separate hospitalization will be counted as a separate line in the database. Bias is
expected to be minimal as long-term use of AST will exclude the subsequent hospitalization
periods because the patient would not be naive to AST on admission.
The sample size of the dataset is not limited for ASTRA-1 in order to provide the maximum
power to the study, but will include a minimum of 5000 patients.
The datasets, along with covariates and related data, will be anonymized by Custodix, a
Trusted Third Party, experienced in anonymizing hospital data. All anonymized datasets will
be linked by the trusted third party over the anonymized patient number with the anonymized
IMS-database of ambulatory dispensed medication. All further queries will be performed on
this anonymized set of data which combines patients covariates and ambulatory consumption of
relevant medication.
Patients on long-term ambulatory AST (defined as continued use during > 3 months) without
ambulatory use before hospitalization are the ones we would like to investigate in the
primary endpoint analysis of this study.
We will determine the number of those patients vs. all discharged adult patients and also
vs. the number of adult patients with AST treatment at any moment during hospitalization.
More in detail, descriptive statistics will be carried out using appropriate parametric or
non- parametric tests (Student t-test or Mann-Whitney U-test, based on distribution of data)
to describe the demographics of the included patients.
Patients will be divided in 3 groups: 1) patients on AST before admission (whether therapy
is stopped or continued during hospitalization), 2) patients started on AST during
hospitalization but stopped before or at discharge and 3) patients started on AST during
hospitalization and continued use after discharge. For patients in group 3, we will describe
what the proportion of patients is with use of AST at +1, 3, 6 and 12 months after
discharge, therefore group 3 will be subdivided along with these proportions.
To investigate potential risk factors correlating with long-term use, groups 2 and 3 will be
compared using uni- and multivariate analysis evaluating associated risk factors such as
age, sex, weight, comorbidities, type of wards, and concomitant medication. A subgroup
comparison between groups 2 and 3(b+c+d) will be carried out to discuss risk factors
associated with continued long-term use.
Statistical analysis will be carried out in SPSS or SAS by the investigator in collaboration
with L-Biostat (KU Leuven).
Based on this dataset an estimate on cost of AST from a healthcare payer perspective will be
calculated using the list price (= public price) at 01-07-2013 of the involved medication.
In combination with the results of ASTRA-2 the impact of parameters like percent of
appropriateness, duration of therapy, diagnosis and comorbidities will be studied in a
multivariate analysis. As the main dataset from ASTRA-2 comes from UZ Leuven, the other
participating hospitals are each requested to review 20 medical files from their hospital in
order to investigate possible extrapolation bias or to support the findings.
ASTRA 2
A retrospective, non-interventional, multi-centric study will be carried in the
participating hospitals. Patients will be recruited hospital wide in all participating
hospitals. The main number of inclusions will be in the University hospitals Leuven,
inclusions in other participating hospitals will be used to investigate possible
extrapolation bias and to support the findings.
All hospitalized patients discharged from the participating hospitals from 01-07-2012 until
01-07-2013 will be included. Exclusion of deceased patients, juvenile patients (defined as
younger than 18 years at time of discharge), critically ill patients, patients without a
startup of AST and patients without AST at discharge leads to the subgroup that is subject
of this research. An overview of the inclusion process is given in figure 8.
Patients admitted at the ICU, during hospitalization, will not be included as literature
concerning the use of AST (especially as SUP) in the ICU setting (for critically ill
patients) is already exhaustive 3,15.
Startup or initiation of AST during hospitalization is defined as treatment with a H2A
(ATC-classification A02BA) or a PPI (ATC-classification A02BC) starting from day 3 or later
of the hospitalization period. Patients with H2A/PPI treatment before hospitalization will
be excluded as their AST is not initiated in the hospital.
The patient inclusion will be performed based on queries retrieving data from the hospital
information system (admission and discharge data) and from the CPOE (AST prescriptions) of
the participating hospitals.
When patients were readmitted to the hospital during the study period, the different
hospitalizations will be evaluated separately.
Assessment of appropriateness of AST will be performed by medical record review by trained
staff pharmacists of the participating hospitals, who can be assisted under close
supervision by master students of the Faculty of Pharmaceutical Sciences, and are led by a
validated procedure.
The method of reviewing will be subject to an interrater validity evaluation using
kappa-statistic. The sole intend of the record review is to gather data on the use and
appropriateness of AST medication and will not intervene in any way in the therapy nor the
patient - physicians relationship. Reporting will be anonymous, never on an individual
patient, physician or hospital.
The estimated prevalence of inappropriate AST is unknown. Assuming a worst case scenario of
50 % inappropriate AST, 384 patients would need to be included in the trial for a confidence
interval of 95% (see table below). Assuming a rate of 30 % of inappropriate AST, 323
patients would need to be included. To guarantee this sample size at least 500 medical files
will be screened in order to compensate for potential dropouts. These 500 medical files will
be randomly selected out of all the included patients using a random code generator. In UZ
Leuven at least 500 medical records will be screened, supplementary other participating
hospitals are requested to screen 20 medical files each.
To guarantee a representative sample of the studied population the sample will be checked
for proportional allocation for the baseline variables sex (male/female), age (minus 65
years or older) and admission label (internal or surgical). In order to prevent selection
bias we will not use random sampling with stratified allocation as we plan no intervention
groups.
Factors justifying AST in non-critically ill hospitalized patients are based on a literature
review an will be used for evaluation of appropriateness and pinpointing risk factors for
inappropriate longterm use of AST after hospitalisation.
The impact on cost savings for the hospital population will be studied from the
healthcare-payer perspective. Therefore the official list price for acquisition, which
equals the reimbursement price for hospitalized patients, at 01-07-2013 for the hospital
will be used. In case of inappropriate therapy or late IV/PO switch there is an opportunity
for cost saving. This will be subject to a sensitivity analysis. Besides direct cost savings
there may be a possible long term cost-avoidance, but this is more difficult to calculate
because side-effects of long term therapy are just popping up in research and cannot be
monetized yet.
Extrapolation of the percentage of patient on inappropriate AST in the hospital to
inappropriate continued long-term use will be performed by combining the results of ASTRA-1
and ASTRA-2. In this way the impact on cost from the healthcare payer perspective can be
calculated. In the analysis we will also look at patients compliance, switch to less
expensive products and perform a sensitivity analysis on cost saving as function of timely
stopping the inappropriate therapy.
