Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Heart and Blood Diseases

Breast Neoplasms

Thromboembolism

Venous Thromboembolism

Thrombosis

Embolism

Embolism and Thrombosis

Vascular Diseases

All Drugs and Chemicals

Natriuretic Agents

Reproductive Control Agents

Progestins

Drospirenone

Levonorgestrel

Contraceptive Agents

Contraceptives, Oral

Women who take oral contraceptives containing drospirenone

Women who take oral contraceptives containing levonorgestrel

Women who take oral contraceptives containing other progestogens

Juergen Dinger, MD, PhD

The objective of this study is to characterize and compare the risks of long-term use of oral contraceptives containing drospirenone and of other established oral contraceptives.

The LASS Study is a large, multinational, prospective, controlled, non-interventional, long-term cohort study that follows a series of cohorts. The cohorts consist of new users (first-ever users, switchers and restarters) of three different groups of oral contraceptives (OCs): OCs containing drospirenone (DRSP), OCs containing levonorgestrel (LNG) and OCs containing other progestogens. A "non-interference" approach is used to provide standardized, comprehensive, reliable information on these groups of OCs under routine medical conditions.

The main clinical outcomes of interest for the long-term follow-up are arterial and venous thromboembolism as well as breast cancer. Regular, active contacts with the cohort members (=active surveillance) provide all necessary information on health-related events or changes in health status.

The study is based on the existing long-term EURAS cohorts who are still in follow-up. LASS succeeds EURAS and prolongs the follow-up period for another five years. Total follow-up time of members of the long-term cohorts will be between 6 and 10 years. By means of annual contacts almost all relevant clinical outcomes will be captured. This will be accomplished by contacting the relevant physicians and by reviewing relevant source documents in the case of relevant clinical outcomes.

Long-term Active Surveillance Study for Oral Contraceptives (LASS)

Arterial thromboembolism associated with the use of oral contraceptives containing drospirenone or levonorgestrel or other progestogens.

Venous thromboembolism associated with the use of oral contraceptives containing drospirenone or levonorgestrel or other progestogens.

Breast cancer associated with the use of hormonal contraceptives either containing both drospirenone (DRSP) and ethinylestradiol (EE), levonorgestrel (LNG) or any other hormonal contraceptive without DRSP.

Bayer

Center for Epidemiology and Health Research, Germany

Principal Investigator

ITT population. All study participants were asked for adverse events at each follow-up.

Users of oral contraceptives containing 3 mg DRSP and 30 mcg ethinylestradiol

DRSP/EE

Users of oral contraceptives containing levonorgestrel

OC-LNG

Users of oral contraceptives containing other progestogens

OC-other

Total

Age, Continuous

Sex: Female, Male

Europe

This study was conducted in seven European countries: Austria, Belgium, Denmark, France, Germany, the Netherlands, and UK.

Region of Enrollment

In non-experimental studies the possibility of bias and residual confounding can never be entirely eliminated. The findings may exclude large, but not small relative risks.

Tested null hypotheses: the ATE hazard ratio for DRSP/E2 vs. OCs containing LNG is higher or equal to 2.

Tested null hypotheses: the ATE hazard ratio for DRSP/E2 vs. OCs containing other progestogens is higher or equal to 2.

The number of participants refers to the ITT study population. During the course od the study, women could for example stop use of oral contraception at any point of time. Therefore, the woman-years of exposure for each group are provided in addition.

Arterial Thromboembolism

Tested null hypotheses: the VTE hazard ratio for DRSP/E2 vs. OCs containing LNG is higher or equal to 2.

Tested null hypotheses: the VTE hazard ratio for DRSP/E2 vs. OCs containing other progestogens is higher or equal to 2.

Tested null hypotheses: the breast cancer hazard ratio for DRSP/E2 vs. OCs containing LNG is higher or equal to 2.

Tested null hypotheses: the breast cancer hazard ratio for DRSP/E2 vs. OCs containing other progestogens is higher or equal to 2.

Breast Cancer

Yasmin

Overall Study

Symptoms and General Pathology

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Body Weight

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Fibrinolytic Agents

Anticoagulants

Heparin

Calcium heparin

Heparin, Low-Molecular-Weight

Tinzaparin

Dalteparin

We will explore the multiple myeloma associated thrombosis risk.

Multiple myeloma

Karina Meijer

Main research question:

What is the present venous thrombosis incidence and what are the current practices of prescribing thromboprophylaxis in patients with multiple myeloma (MM)?

Design:

The present study is a retrospective cohort study. The patients will be selected from the electronic patient dossier (EPD) of the University Medical Center Groningen (UMCG). The present study will include newly diagnosed adult patients with a first MM at the UMCG between 1st of January 2014 and 1st of September 2021. The primary outcome of the study is the incidence of venous thromboembolism (VTE) with one year of diagnosis of MM. The investigators will also describe the various thromboprophylaxis regimens used and their corresponding VTE incidence. The secondary outcome will be the incidence of arterial thrombosis (AT) within the same period of time. Possible confounders are the therapy administered for MM, thromboprophylaxis type, age and patient comorbidities. Lastly, the third outcome will be a description of current thromboprophylaxis practices in the UMCG. Each outcome will be described separately.

Expected results:

Based on the study by de Waal et al in which they included 474 MM patients treated at the UMCG and at 4 hospitals in the province Friesland, the investigators expect to record a VTE incidence of approximately 15%.

Background:

Multiple myeloma (MM) is a neoplastic clonal proliferation of plasma cells causing a considerable worldwide burden of disease. In 2016 Western Europe was one of the regions with the highest MM incidence globally, with an age-standardized incidence of 4.6 per 100.000 (95% UI, 3.7-5.5). MM is associated with multiple complications which make the management of this disease particularly difficult. Moreover, patients with MM have a raised risk of venous thromboembolism (VTE) which substantially increases their mortality risk. The link between malignancy and the development of a hypercoagulable state has been extensively studied, with altered coagulation, patient comorbidities, tumour characteristics and treatment side-effects all playing a role in the pathogenesis of thrombosis in cancer. Specifically in MM, the increased VTE risk seems to be partially due to aberrations in haemostasis, such as acquired activated Protein C resistance and increased levels of Factor VIII and Von Willebrand Factor.

MM treatment and maintenance therapy has developed and improved substantially during the past decades, with immunomodulatory drugs (IMIDs), namely lenalidomide- or thalidomide-based regimens, being currently the most effective and used option. Nevertheless, one of the challenges of these regimens remains the associated elevated VTE risk, which is especially high in newly diagnosed MM patients treated with IMIDs and dexamethasone. Various mechanisms have been researched to explain the increased VTE risk. For instance, transiently decreased thrombomodulin levels during the first months of treatment have been associated with an increased thrombosis risk during the initial period of therapy. Moreover, high levels of cathepsin G have also been hypothesized to contribute to the high thrombosis incidence in MM patients undergoing treatment.

Choosing an appropriate thromboprophylaxis regimen in MM patients treated with IMIDs remains a challenge in clinical practice. Randomized controlled trials (RCTs) did not show a difference in the VTE risk between the use of aspirin or low molecular weight heparin (LMWH) in the management of MM patients. Furthermore, despite thromboprophylaxis, high VTE incidence remains a concerning problem in contemporary lenalidomide-based regimens. Therefore, the current study seeks to describe the use and efficacy of current thromboprophlaxis regimens in MM patients treated with IMIDs in an university medical center in order to assess the current VTE incidence and the effectiveness of thromboprophylaxis protocols in place.

Research question:

What is the present venous thrombosis incidence and what are the current practices of prescribing thromboprophylaxis in patients with multiple myeloma?

Design:

The present study is a retrospective cohort study. The patients will be selected from the electronic patient dossier (EPD) of the University Medical Center Groningen (UMCG). The present study will include newly diagnosed adult patients with a first MM at the UMCG between the 1st of January 2014 and 1st of September 2021. The primary outcome of the study is the incidence of VTE with one year of diagnosis of MM. The investigators will also describe the various thromboprophylaxis regimens used and their corresponding VTE incidence. The secondary outcome will be the incidence of arterial thrombosis (AT) within the same period of time. Possible confounders are the therapy administered for MM, thromboprophylaxis type, age and patient comorbidities. Lastly, the third outcome will be a description of current thromboprophylaxis practices in the UMCG. Each outcome will be described separately.

Expected results:

Based on the study by de Waal et al in which they included 474 MM patients treated at the UMCG and at 4 hospitals in the province Friesland, the investigators expect to record a VTE incidence of approximately 15%.

Thrombosis in Patients With Multiple Myeloma in an University Medical Center

Thrombosis in Newly Diagnosed Multiple Myeloma Patients: a Clinical Audit of Intermediate Dose Low Molecular Weight Heparin

We will investigate the frequency of thrombosis events per thromboprophylaxis regimen.

We will calculate the incidence of venous thromboembolism of patients within one year of a first diagnosis of multiple myeloma. The influence of various risk factors will be investigated.

We will calculate the incidence of arterial thromboembolism of patients within one year of a first diagnosis of multiple myeloma. The influence of various risk factors will be investigated.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Long-term Active Surveillance Study for Oral Contraceptives (LASS)	NCT00676065	Arterial Thromb... Venous Thromboe... Breast Cancer		-	Center for Epidemiology and Health Research, Germany
Thrombosis in Patients With Multiple Myeloma in an University Medical Center	NCT05541978	Multiple Myelom... Venous Thromboe... Arterial Thromb...	Multiple myelom...	-	University Medical Center Groningen

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