Heart and Blood Diseases

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Thrombosis

Venous Thrombosis

Lung Diseases

Pulmonary Embolism

Embolism

Thromboembolism

Respiration Disorders

Respiratory Tract Diseases

Embolism and Thrombosis

Vascular Diseases

All Drugs and Chemicals

Hematinics

Bone Density Conservation Agents

Fluorodeoxyglucose F18

Calcium

Liver Extracts

Calcium, Dietary

Complete clinical history, along with routine physical, analytical examination (creatinine, sodium, potassium, red series, white series, liver and calcium profile) and chest x-ray.

Limited screening plus positron emission tomography / computed tomography with 18 FDG (18FDG PET-CT).

The performance of the 18 FDG PET-CT will require fasting of at least 6 hours, and the glycemia will have to be lower than 126 mg / dL before the injection of 3-5 MBq / kg of 18FDG. Intravenous injection will follow a period of approximately 60 minutes in a quiet room.

Computed tomography (CT) will be performed from the middle of the forehead to the feet with normal and shallow breathing using a low dose adjustment Iodinated contrast will not be administered intravenously.

Fludeoxyglucose 18F

Luis Jara Palomares, MD/PhD

Clara M Rosso Fernández, MD/PhD

Juan José López Núñez, MD

Gloria de la Red Bellvis, MD

Luis Jara-Palomares, MD

Jesús Aibar Gallizo, MD

Marina Suarez Pinera, MD

Diego Agustin Rodríguez, MD

Fátima del Molino Sanz, MD

Carmen Díaz Pedroche, MD

Alicia Lorenzo Hernández, MD

Vladimir Salazar Rosa, MD

Open and multicenter randomized clinical trial (1:1) comparing limited screening with extended screening with the performance of Positron emission tomography-computed tomography (PET-CT) scan in the search for neoplasms in patients with unprovoked venous thromboembolic disease at high risk of developing cancer at follow-up.

Introduction: Cancer screening in patients with unprovoked venous thromboembolic disease (VTE) is controversial. In the last years, a score has been developed that selects patients at high risk of developing cancer during follow-up.

Objective: To estimate the impact of an active cancer search strategy using 18-fluordesoxiglucose (FDG) PET-CT in unprovoked VTE with high-risk to develop cancer.

Specific Objectives: 1) Number of neoplasms diagnosed in the screening process: 2) number of neoplasms diagnosed at an early stage, 3) impact on survival of the strategy; and 4) impact on the quality of life.

Cancer will be considered from 30 days up to 12 months after the diagnosis of VTE.

Scope: 20 Spanish hospitals. Design: Open-label, multicentre Randomized clinical trial (1: 1) comparing the performance of PET-CT versus limited screening for cancer.

Population: Patients older than 18 years with unprovoked VTE at high risk of presenting cancer at follow-up (≥3 points in the score of Jara-Palomares et al., Chest 2017).

Follow-up: 12 months after VTE. Sample: The sample size calculated is 650 patients, to obtain a power of 80%, with a level of significance of 5%, and taking into account a 10% loss of follow-up.

Screening for Cancer in Patients With Unprovoked VTE

PET / CT Scan to Detect Cancer in Patients With Unprovoked Venous Thromboembolic Disease. Open Randomized Clinical Trial.

IPD to be shared with the center participants once the study is officially finished in the foreseen period of three years.

Estimate the impact of an active cancer search strategy using PET-CT in the number of neoplasms diagnosed in the screening process in patients with high-risk unprovoked thromboembolic disease.

Estimate the impact of an active cancer search strategy using PET-CT in the number of neoplasms diagnosed in early phase in the screening process in patients with high-risk unprovoked thromboembolic disease.

Estimate the impact of an active cancer search strategy using PET-CT in the overall survival in patients with high-risk unprovoked thromboembolic disease.

Estimate the impact of an active cancer search strategy using PET-CT in the quality of life evaluated with the scale EQ-5D in patients with high-risk unprovoked thromboembolic disease. The EQ-5D consists of 2 parts - the "Descriptive System" and the "Visual Analogue scale". The DS comprises 5 dimensions (mobility, self care, usual activities, pain/discomfort, anxiety/depression). Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems.

The EQ VAS records the respondent's self-rated health on a 20 cm vertical, visual analogue scale with endpoints labelled 'the best health you can imagine' and 'the worst health you can imagine'. This information can be used as a quantitative measure of health as judged by the individual respondents.

Fundación Pública Andaluza para la gestión de la Investigación en Sevilla

Blood and Lymph Conditions

Symptoms and General Pathology

Neoplasms

Thrombocytopenia

Hemorrhage

Hematologic Neoplasms

Venous Thromboembolism

Blood Platelet Disorders

Hematologic Diseases

Cytopenia

All patients 18 years and older admitted to an adult intensive care unit during the current admission episode and that also had an active HM / HCT diagnosis.

We plan to the analyze patients outcomes according to:

1. Thrombocytopenia We will analyze bleeding and thrombosis risk taking into account platelets levels.
2. Patients receiving thromboprophylaxis (VTE vs Bleeding)

Venous thromboembolism (VTE) is the second leading cause of death in patients with cancer, after disease progression. VTE is increasingly recognized as a complication in patients with hematologic malignancies and various studies have reported high rates of VTE. Critically ill patients are at high risk of VTE and should all receive thromboprophylaxis. Given the increasing number of patients with HM (hematologic malignancies) / HCT (Hematopoietic cell transplantation) who develop critical illness, and their often prolonged course, it is imperative to understand the incidence and risk factors for VTE, and to evaluate the efficacy and risks associated with both chemical and mechanical thromboprophylaxis Therefore, the investigators plan to evaluate retrospectively the VTE / PE (pulmonary embolism) incidence in HM /HCT patients at the University of Toronto, and the complications associated with it (including death). In addition, the investigators want to evaluate the use, type (mechanical or pharmacological) and timing of thromboprophylaxis. And lastly, the investigators will determine the incidence of bleeding and of complications associated with chemical and mechanical thromboprophylaxis. The investigators will describe the change in VTE incidence over the last 10 years.

The investigators know that patients with COVID-19 infection are at higher risk of thrombosis than non-COVID patients. As such, HM/HCT COVID-19 pts will comprise a subgroup, which will be compared with patients who are not not positive for COVID-19. If these numbers are low, COVID-19 status will be included as a predictive variable in our modelling.

The results of this research program will help define indications and safety of VTE prophylaxis; and will inform the development of clinical practice guidelines.

2.0 BACKGROUND AND SIGNIFICANCE Venous thrombosis is a disease of aging, with a low rate of about 1 per 10,000 annually before the fourth decade of life, rising rapidly after age 45 years, and approaching 5-6 per 1000 annually by age 801. The most common risk factors are hospitalization, cancer and surgery. Up to 20% of patients admitted to a medical service will have thrombosis and up to 40% of those admitted to a surgical service. About 10% of all deaths in hospitals are related to pulmonary embolism, and many times it was not suspected before death.

Venous thromboembolism (VTE) is the second leading cause of death in patients with cancer, after disease progression2. The incidence of venous thrombosis during the first 6 months after cancer diagnosis is 12.4 per 1000, with varying incidences depending of the type of cancer, i.e., cancers of the bone (56/1000), ovary (45/1000), uterus (38/1000), Hodgkin's lymphoma (36/1000), breast (35/1000) and brain (32/1000) had the highest incidence. Cancers of the ovary, pancreas, lung, stomach, and hematological malignancies tend to present a high incidence of venous thromboembolism in the year before the cancer diagnosis.

VTE is increasingly recognized as a complication in patients with hematologic malignancies and various studies have reported high rates of VTE. Another high risk population for bleeding and DVT is the HSCT (hematopoietic stem cell transplant), with a 3.7% 1-year incidence of VTE, and 8-20% incidence of catheter-related thrombosis (CRT)3. In addition to a risk of thrombosis, HSCT recipients also have an increased risk of bleeding because of prolonged and severe thrombocytopenia. The initiation of therapeutic anticoagulation during days 1-180 after HSCT was the strongest predictor of bleeding (odds ratio (OR) 3.1\[95% confidence interval (CI) 1.8-5.5)\].

The timing of hemostatic complications is also an important consideration as bleeding events are more likely to occur early in the post-transplant course when patients are profoundly thrombocytopenic, whereas thrombotic events occur more frequently after hematopoietic recovery Critically ill patients are at high risk of VTE and should all receive thromboprophylaxis. Patients with HM or HCT who are thrombocytopenic (platelets \<30) are ineligible for pharmacologic prophylaxis because of the high risk of bleeding. In these patients, it has been suggested to apply mechanical antithrombotic measures 4, but not all centers have sequential compression devices (SCD). In the general population of patients admitted to the hospital, it has been suggested that SCDs do not reduce the risk of VTE 5. In critically ill patients, evidence of benefit of SCD use is lacking. Further, their use is associated with costs, discomfort, skin breakdown, and mobility restrictions. In healthcare settings lacking SCDs, patients receive no thromboprophylaxis until the platelet count recovers.

Early after chemotherapy or HCT, two recent studies in non-ICU patients suggest that rates of non catheter-related VTE are low, raising the question of whether any prophylaxis is required. In a prospective study of 1,072 consecutive adult cancer patients, only 30 VTE events were observed during follow-up, 5 (2.3%) in HM patients and 25 (2.9%) in solid tumor patients (relative risk \[RR\]: 0.79, 95% CI: 0.30-2.03; p=.79) (2). Four of the five episodes in HM patients were related to a catheter. Major bleeding was infrequent in both groups (1.8 vs. 3.9%; RR: 0.48, 95% CI: 0.17-1.33; p=.21), and thromboprophylaxis was not associated with an increased incidence of major bleeding.

While thromboprophylaxis may not be necessary in non-ICU patients, data in critically ill patients regarding the incidence of VTE, effectiveness of thromboprophylaxis, and bleeding risk, is lacking. Moreover, the risk of VTE may be higher later in the course, when the platelet count recovers, or in patients with graft vs host disease or sinusoidal obstructive syndrome.

Given the increasing number of patients with HM/HCT who develop critical illness, and their often prolonged course, it is imperative to understand the incidence and risk factors for VTE, and to evaluate the efficacy and risks associated with both chemical and mechanical thromboprophylaxis.

3.0 HYPOTHESES AND SPECIFIC AIMS 3.1 Specific Aim 1 Determine the use, type (mechanical or pharmacological) and timing of thromboprophylaxis.

3.2 Specific Aim 2 Determine incidence of catheter and non catheter-related VTE (upper / lower extremity DVT and PE) and explore variables that are independently associated with it.

3.3 Specific Aim 3 Determine incidence of bleeding, complications associated with SCDs, and complications associated with VTE, including death. Bleeding severity will be classified according to current accepted standards6.

3.4 Hypothesis In critically ill patients with hematologic malignancy (HM) who are thrombocytopenic, venous thromboembolism (VTE) is infrequent within the first 30 days following induction chemotherapy or hematopoietic cell transplant (HCT), rendering it possible to avoid the use of thromboprophylaxis (mechanical or pharmacological) and the associated risks (i.e. serious bleeding).

The investigators propose a program of research on VTE in HM/HCT patients. This program consists of several projects which will inform the design of a future international multi-center RCT. It will consist of three consecutive phases:

1. To conduct a systematic review to evaluate the incidence and timing of VTE, and the threshold for initiation of chemical thromboprophylaxis.
2. To evaluate retrospectively VTE incidence in HM / HCT patients at the University of Toronto.
3. To design a 2-center pilot feasibility RCT of sequential compression devices (SCD) versus no thromboprophylaxis in thrombocytopenic HM/HCT patients admitted to ICU.

Regarding the second objective, the investigators will perform a retrospective analysis of VTE incidence in HM/HCT patients at University of Toronto.

Venous Thromboembolism in Hematologic Malignancy and Hematopoietic Cell Transplant Patients: a Retrospective Study

Venous Thromboembolism in Hematologic Malignancy and Hematopoietic Cell Transplant Patients: a Retrospective Study of Thrombosis / Bleeding Incidence and Prophylaxis Trends

No individual patient information will be included in the analysis. All data will be anonymized.

The primary outcome will be the number of patients who suffered a catheter and non catheter related VTE (upper/lower extremity DVT and PE) during their ICU admission. For DVT diagnosis venous ultrasonography is the first-line imaging test. Alternative imaging modalities will include computed tomographic imaging, magnetic resonance (MR) imaging, and contrast computed tomography (CT)(12). For the diagnosis of PE, confirmatory imaging (i.e., CT pulmonary angiography, ventilation-perfusion scan) will be required for definitive diagnosis

Frequency of use, type (mechanical or pharmacological) and timing of thromboprophylaxis

No bleeding, Minor bleeding or major bleeding, collected from chart review.

Discharge to home, transfer to another hospital, transfer to rehabilitation facility, death

Mount Sinai Hospital, Canada

Lung Neoplasms

Fibrinolytic Agents

Anticoagulants

Heparin

Rivaroxaban

Calcium heparin

Heparin, Low-Molecular-Weight

Tinzaparin

Dalteparin

Patients will undergo a bleeding risk assessment to determine their entering VTE prophylaxis. Low bleeding risk patients will have once daily sc LMWH prophylaxis. Intermediate bleeding risk patients will have q 12 h sc low dose unfractionated heparin prophylaxis. High bleeding risk patients will have mechanical prophylaxis. Assigned prophylaxis can be interrupted as clinical judgement requires, e.g., for peri-procedural reasons. When patients are discharged, if they have low risk of bleeding at the time of discharge, whatever their bleeding risk assessment at the time of randomization, will begin 5 mg rivaroxaban prophylaxis (two 2.5 mg tablets) once daily with food, starting on the day of discharge, for 15 days.

VTE risk assessment and prophylaxis if indicated during hospitalization according to current policies for hospitals in China but no further treatment prophylaxis after discharge.

At admission, patents undergo bleeding risk assessment and receive prophylaxis according to bleeding risk. After discharge, they will undergo an extended treatment of 5mg Rivaroxaban once daily for 15 consecutive days,

Bleeding-risk based prophylaxis strategy during hospitalization and extended pharmacological treatment after discharge

Patients randomized to the standard treatment (Control) group will receive routine VTE prophylaxis according to current guidelines and clinical practices, VTE risk assessment and prophylaxis if indicated during hospitalization according to current policies for hospitals in China but no further treatment prophylaxis after discharge

Routine VTE prophylaxis in hospital

Zhenguo Zhai, Doctor

Venous thromboembolism (VTE) is a common complication of malignancies, in particular to lung cancer. Patients with lung cancer in surgical and medical departments are at high risk of VTE development. Prophylaxis is one major way to to prevent it. Currently, VTE prophylaxis is mainly based on VTE-risk assessment. However, all patients hospitalized for cancer are at intermediate or high risk of VTE but their bleeding risk vary. To improve effect of VTE prophylaxis and reduce bleeding events in patients with lung cancer, we will conduct an open-label parallel randomized clinical tria to assess the effect of bleeding risk based prophylaxis strategy among lung cancer patients. We hypothesize that VTE prophylaxis based on bleeding risk assessment with a short post-discharge treatment course is superior to VTE propohylaxis based on VTE risk assessment among hospitalized patients with lung cancer

A sample of 3200 eligible patients will be randomized into experimental or control group with an allocation rate of 1:1. Stratified by medical/surgical units, block randomization with a varying block size of 4 or 6 will be adopted to randomize patients into experimental or control group. In experimental group, patients will undergo bleeding risk assessment and receive prophylaxis according to bleeding risk during hospitalization, and they will also receive an extended pharmacological prophylaxis of 5mg Rivaroxaban once daily for up to 15 consecutive days after discharge. In control group, patients will receive routine VTE prophylaxis, VTE risk assessment and prophylaxis if indicated during hospitalization according to current policies for hospitals in China but no further treatment prophylaxis after discharge.

Patients in both groups will be followed up for 30 days. The primary outcome is symptomatic and asymptomatic objectively proven VTE (deep vein thrombosis (DVT) and/or pulmonary embolism (PE)) within 30 days after initiation of randomization. Ultrasound and CTPA will be performed to detect DVT and PE, respectively. Clinically relevant bleeding (non-major clinically relevant and major bleeding, HIT) and death are secondary outcomes.

Randomization and sequence generation A computerized random-number generator will be used to generate the allocation sequence. In this multicenter trial involving 10 hospitals, randomization procedures will be organized centrally.

Stratified block randomization with a varying block size of 4 or 6 will be used to allocate patients into experimental or control group. Patients with lung cancer will be stratified into those under planned medical or surgical treatments.

In each stratum, patients will be blocked according to their admission sequence. Four or six patients consecutively admitted will be one block depending on the block size. In each block, patients will be randomly allocated into experimental or control group according to sequence generated in advance by software.

Allocation concealment/Blinded randomization Patient assignments will be enclosed in a sequentially numbered, opaque, sealed envelopes (SNOSE). Clinicians in charge of patient enrollment will not know the allocation sequence until eligible patients who meet inclusion and exclusion criteria are enrolled.

An independent statistician will generate the random allocation sequence. Physicians will enroll participants and assign interventions in experimental or control group.

Blinding/Open label This is an open-label trial that patients, clinicians and researchers will know allocation assignments after enrollment. But imaging experts providing the duplex ultrasound and CTPA results will be blinded in order to objectively assess the 30-day CTPA-proven VTE incidence and other outcomes in both groups. An independent data monitoring board will evaluate the trial data and safety.

CHIPs-VTE Study in Hospitalized Patients With Lung Cancer

Bleeding Risk Guided VTE Prophylaxis Strategy for Hospitalized Patients With Lung Cancer: Rationale and Design for a Multicenter, Adjudicator-blinded, Parallel, Randomized Clinical Trial in China

PE incidence detected by CTPA and/or DVT by ultrasound

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Screening for Cancer in Patients With Unprovoked VTE	NCT03937583	Venous Thromboe... Respiratory Dis... Pulmonary Disea... Deep Venous Thr... Pulmonary Embol... Screening Undefined	Fludeoxyglucose...	18 Years -	Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Screening for Cancer in Patients With Unprovoked VTE	NCT03937583	Venous Thromboe... Respiratory Dis... Pulmonary Disea... Deep Venous Thr... Pulmonary Embol... Screening Undefined	Fludeoxyglucose...	18 Years -	Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Venous Thromboembolism in Hematologic Malignancy and Hematopoietic Cell Transplant Patients: a Retrospective Study	NCT05396157	Thrombosis, Ven... Bleeding Hemorr... Venous Thromboe... Hematologic Mal... Thrombocytopeni...		18 Years -	Mount Sinai Hospital, Canada
CHIPs-VTE Study in Hospitalized Patients With Lung Cancer	NCT04158973	Venous Thromboe... Pulmonary Embol... Deep Venous Thr...	Bleeding-risk b... Routine VTE pro...	40 Years -	China-Japan Friendship Hospital

Spots Global Cancer Trial Database for venous thromboembolic disease