Study type

Study topic

Disease /health condition
Human medicinal product

Study type

Non-interventional study

Scope of the study

Safety study (incl. comparative)

Data collection methods

Secondary use of data
Non-interventional study

Non-interventional study design

Cohort
Study drug and medical condition

Name of medicine

DOPTELET

Study drug International non-proprietary name (INN) or common name

AVATROMBOPAG MALEATE

Anatomical Therapeutic Chemical (ATC) code

(B02BX08) avatrombopag
avatrombopag

Medical condition to be studied

Chronic disease
Thrombocytopenia

Additional medical condition(s)

severe chronic liver disease
Population studied

Short description of the study population

The source population will consist of patients under the care of physicians practising at hospitals or specialised outpatient settings (hospitals or specialty clinics) in European countries, where patients are being treated for severe thrombocytopenia due to severe CLD (chronic liver disease) in preparation for an elective invasive procedure.
The study population will comprise adult patients with documented severe CLD (Child-Pugh C or Model of End-Stage Liver Disease (MELD) score > 24) and severe thrombocytopenia (platelet count < 50 x 109/L) initiating treatment with avatrombopag or lusutrombopag or receiving a platelet transfusion in preparation for an elective invasive procedure during the study period.
Follow-up will start on the index date and end at the earliest of (1) 30 days after the date of the elective invasive procedure for patients who had a procedure within 15 days of the end of treatment or 30 days after the last date of treatment for patients who did not have a procedure within 15 days after the end of treatment, (2) death, or (3) loss to follow-up.

Age groups

Adult and elderly population (≥18 years)
Adults (18 to < 65 years)
Adults (18 to < 46 years)
Adults (46 to < 65 years)
Elderly (≥ 65 years)
Adults (65 to < 75 years)
Adults (75 to < 85 years)
Adults (85 years and over)

Special population of interest

Hepatic impaired

Estimated number of subjects

30
Study design details

Study design

Non-interventional, multinational descriptive cohort study based on secondary data collected from patients' medical notes who are treated with avatrombopag or lusutrombopag and patients receiving platelet transfusions in routine clinical practice at sites in Austria, Denmark, Netherlands and Spain.

Main study objective

The primary study objective is to estimate, among patients with severe CLD and severe thrombocytopenia who are scheduled for an elective invasive procedure, differences between LFT values measured before and after the elective invasive procedure, according to the treatment received (i.e., avatrombopag, lusutrombopag, or platelet transfusion).

Setting

The study will be conducted in hospital or specialised outpatient settings (hospitals or specialty clinics) where patients with severe CLD and thrombocytopenia are treated in preparation for an elective invasive procedure.
At each site, a study investigator will be identified to facilitate collection of patients’ data from medical records and, as needed, support the ethics committee submission as required by local policies. Access to data from both hospital and outpatient/primary care settings would be desirable if postprocedure or posttreatment follow-up visits and laboratory test monitoring occur in a different healthcare setting (e.g., primary care).

Outcomes

The primary study outcome will be liver function measured through biochemical LFTs before and after the elective invasive procedure as recorded in each patient’s medical record. The difference between LFT values measured before and after the procedure, i.e., preprocedure and postprocedure values, will be described according to the treatment received. The preprocedure LFT values used for this analysis will be the measurement before and closest to the procedure date, and the postprocedure LFT values will be the last one measured after the procedure within the defined follow-up window.
Secondary study outcomes will include (1) ascites and encephalopathy, which are considered significant complications of CLD to be assessed in the 3 treatment cohorts, and (2) ADRs attributed to avatrombopag. The frequency and severity of ascites and hepatic encephalopathy will be described before and after the procedure (and before and after treatment), according to the treatment received, based on information recorded in patients’ medical records. Several clinical scales are available using various measures for grading ascites and hepatic encephalopathy that might be used in clinical practice. However, we propose to measure both ascites and encephalopathy following the classification of severity proposed in the Child-Pugh classification of cirrhosis (absent, slight, and moderate for ascites; none, grade 1 to 2, and grade 3 to 4 for encephalopathy). We anticipate that clinical use and actual recording of any measurement tool for ascites and encephalopathy in patients’ records may be limited in routine clinical practice settings.

Data analysis plan

The analyses will be descriptive and will be performed separately for each exposure cohort. Patients initiating avatrombopag or lusutrombopag and patients undergoing platelet transfusions will be characterised in terms of demographic and clinical characteristics such as severity of CLD and thrombocytopenia, history of previous treatments with the same indication, comorbidities, use of comedications, and type of elective invasive procedure. For continuous variables, descriptive statistics will include the mean, SD, median, first and third quartiles, and minimum and maximum values. For categorical variables, descriptive statistics will include frequencies and percentages. For variables with missing data, the count and percentage of missingness will be reported for each variable. LFT values will be characterised by cohort and by period. Counts and proportions of patients that do not have LFTs recorded during follow-up will be calculated.