Clinical trial NCT06872541: Evaluation of Platelet Aggregability in Patients with Non-small Cell Lung Carcinomas
Official title: Evaluation of Platelet Aggregability in Patients with Non-small Cell Lung Carcinomas
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Assessment of Platelet Aggregability in Patients Patients with Non-small Cell Lung Carcinoma
Lead sponsor: University of Sao Paulo
Sponsor class: OTHER
First posted: 2025-03-12
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: Cancer patients are at greater risk of experiencing events thrombotic, arterial or venous, during the course of the disease. Specifically in lung cancer, patients are seven times more prone to developing venous thrombosis, when compared to general population. Platelets influence cancer progression and Tumor microenvironment facilitates platelet activation. Therefore, the main objective of this project is to evaluate platelet aggregation analyzed by aggregometry optics with the use of AggRAM® equipment in patients diagnosed recent non-small cell lung carcinomas, prior to any oncological treatment. Among the secondary objectives, it stands out analyze the primary objective using the PPAnalysis® method (method in developed by our group in partnership with the University of Readings (UK), Plateletworks® and Chrono-log. This is a case-control study, with groups differentiated by the presence or absence of malignant lung neoplasia and matched by age, sex and presence or absence of smoking in the previous 6 months to inclusion. Patients diagnosed with non-cell lung carcinoma Small children without prior treatment will be candidates for participation in the study.

It is expected that at the end important aspects related to aggregation platelet disease are better characterized in this neoplasm, the most important cause of death from cancer in the world, and therapeutic strategies to improvement in morbidity and mortality in the disease can be developed.

Detailed description: Cancer patients are at increased risk of thrombotic complications, especially venous thromboembolism (VTE). The oncology population is seven times more likely to develop thrombosis when compared to the general population, with an incidence of up to 20% of patients during follow-up. It is suggested that the reasons for this greater thrombotic risk are immobility, invasive procedures and changes in coagulation, in addition to possible disorders of platelet aggregation and endothelial function.

The literature suggests that the basic thromboembolic mechanism would be related to the production, by tumor cells, of pro-coagulant factors such as tissue factor and neoplastic pro-coagulant. PAI-1, the main inhibitor of the plasminogen activator pathway, is also produced by tumor cells. Still, tumor production of factors inhibiting the fibrinolytic system plays a role in hypercoagulability and may contribute to tumor angiogenesis. Regarding arterial thrombotic events, although there is no unanimity regarding the causal relationship between the pathologies, epidemiological data strongly suggest that this complication is more common in patients with cancer, compared to the population without the disease.

It is worth mentioning that lung cancer is the most common cause of cancer deaths in the world. It is possible that the high mortality from lung cancer is related, at least partially, to the higher incidence of thrombotic complications presented by these patients, compared to those with other types of cancer. Although VTE is one of the main causes of morbidity and mortality in cancer patients, the use of anticoagulants as primary prophylaxis is not routinely recommended.

The pathophysiological mechanisms involved in the increased risk of thromboembolic events in cancer patients, especially with lung cancer, which, as mentioned, present, in addition to the aggressiveness of the disease itself, a higher incidence of thrombotic events, are still little known. The main objective of this project is to contribute to a better understanding of the mechanisms involved in thrombotic events in the population with lung cancer, with clear therapeutic impacts.

This is a case-control study with groups differentiated by the presence or absence of NSCLC and matched by age, sex and presence or absence of smoking in the 6 months prior to inclusion. Patients diagnosed with NSCLC without prior treatment for the disease will be candidates for participation in the study.

The primary objective is to compare platelet aggregability by optical aggregometry assessed by the AggRAM® method in patients diagnosed with NSCLC, prior to any oncological treatment, in relation to a control group matched by sex, age and presence or absence of smoking in the previous 6 months. to inclusion Secondary objetives includes laboratorial test of inflammation, coagulation and subgroup analysis.

Eligibility criteria: Inclusion Criteria:

* Patients \> 18 years old;
* Confirmed diagnosis of non-small cell lung carcinoma in the case group; absence of history of any neoplasia for control group
* Agreement to sign the Free and Informed Consent Form

Exclusion Criteria:

* Anticoagulation in the last 30 days;
* Use of any antiplatelet agent in the last 30 days;
* Use of any non-steroidal anti-inflammatory drugs in the last 30 days;
* Known platelet dysfunction or platelets \<100,000/mm3 or \>450,000/mm3;
* Creatinine clearance by MDRD \<30 ml/min/1.73 m2
* Eastern Cooperative Oncology Group Performance Status Scale (ECOG) \>2
* Known coagulation disorder;
* Hematocrit less than 34% or greater than 55%

Primary outcomes:
measure: Platelet Aggregation analyzed by optical aggregometry-ADP (AggRAM™- Helena Laboratories)
timeFrame: 14 days
Secondary outcomes:
measure: Platelet aggregability by AggRAM™ ADP after 14 days of use of Clopidogrel 75 mg/day
timeFrame: 14 days
measure: Platelet aggregability by Plateletworks-ADP at baseline and after 14 days of use of Clopidogrel 75 mg/day
timeFrame: 14 days
measure: Serum levels of tissue factor
timeFrame: Baseline
measure: Serum levels of type I plasminogen activator inhibitor (PAI 1)
timeFrame: Baseline
measure: Serum levels of immature platelets
timeFrame: Baseline
measure: Serum levels of ultrasensitive C-reactive protein (hs-CRP);
timeFrame: Baseline
measure: Serum levels of interleukin 6
timeFrame: Baseline
measure: Serum levels of Interleukin 1
timeFrame: Baseline
measure: Serum levels of P-Selectin
timeFrame: Baseline
measure: Serum levels of D-dimero
timeFrame: Baseline
measure: Serum levels of Lipoprotein(a) (LPa)
timeFrame: Baseline
measure: Serum levels of Glycated hemoglobin
timeFrame: Baseline
measure: Serum levels of coagulogram
timeFrame: Baseline
measure: Serum levels of Fibrinogen
timeFrame: Baseline
measure: Serum levels of cholesterol ester transfer proteins
timeFrame: Baseline
measure: Serum levels of blood count with platelets
timeFrame: Baseline
Other outcomes:
measure: Subgroup Analysis- Age
timeFrame: Baseline and 14 days
measure: Subgroup Analysis- Sex
timeFrame: Baseline and 14 days
measure: Subgroup Analysis- Diabetes mellitus
timeFrame: Baseline and 14 days
measure: Subgroup Analysis-Glomerular filtration rate
timeFrame: Baseline and 14 days
measure: Subgroup Analysis- BDI
timeFrame: Baseline and 14 days
measure: Subgroup Analysis- Smoking
timeFrame: Baseline and 14 days
Locations:
city: São Paulo
country: Brazil
facility: Heart Institute (InCor) / University of São Paulo
Study officials:
References:
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