Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| control (group 1) | Active Comparator | patients without NSCLC and matched by age, sex and presence or absence of smoking in the 6 months before inclusion |
|
| case (group 2) | Active Comparator | patients with NSCLC and matched by age, sex and presence or absence of smoking in the 6 months prior to inclusion |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Clopidogrel | Drug | Clopidogrel 75 mg uma vez ao dia durante 14 dias |
|
| Measure | Description | Time Frame |
|---|---|---|
| Platelet Aggregation analyzed by optical aggregometry-ADP (AggRAM™- Helena Laboratories) | Compare platelet aggregation analyzed by optical aggregometry-ADP (AggRAM™- Helena Laboratórios) between both groups | 14 days |
| Measure | Description | Time Frame |
|---|---|---|
| Platelet aggregability by AggRAM™ ADP after 14 days of use of Clopidogrel 75 mg/day | Evaluation of Platelet aggregability by AggRAM™ ADP after 14 days of use of Clopidogrel 75 mg/day | 14 days |
| Platelet aggregability by Plateletworks-ADP at baseline and after 14 days of use of Clopidogrel 75 mg/day |
| Measure | Description | Time Frame |
|---|---|---|
| Subgroup Analysis- Age | Age (≥65 years or < 65 years) | Baseline and 14 days |
| Subgroup Analysis- Sex | Sex (male/female) | Baseline and 14 days |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Heart Institute (InCor) / University of São Paulo | São Paulo | São Paulo | Brazil |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28402864 | Background | Fuentes HE, Oramas DM, Paz LH, Casanegra AI, Mansfield AS, Tafur AJ. Meta-analysis on anticoagulation and prevention of thrombosis and mortality among patients with lung cancer. Thromb Res. 2017 Jun;154:28-34. doi: 10.1016/j.thromres.2017.03.024. Epub 2017 Apr 1. | |
| 22345488 | Background | Mutlu H, Artis TA, Erden A, Akca Z. Alteration in mean platelet volume and platicrit values in patients with cancer that developed thrombosis. Clin Appl Thromb Hemost. 2013 Jun;19(3):331-3. doi: 10.1177/1076029611433644. Epub 2012 Feb 16. |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D000077144 | Clopidogrel |
| ID | Term |
|---|---|
| D013988 | Ticlopidine |
| D058924 | Thienopyridines |
| D013876 | Thiophenes |
| D013457 | Sulfur Compounds |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Evaluation of Platelet aggregability by Plateletworks-ADP at baseline and after 14 days of use of Clopidogrel 75 mg/day |
| 14 days |
| Serum levels of tissue factor | Evaluation of Serum levels of tissue factor | Baseline |
| Serum levels of type I plasminogen activator inhibitor (PAI 1) | Evaluation of Serum levels of type I plasminogen activator inhibitor (PAI 1) | Baseline |
| Serum levels of immature platelets | Evaluation of Serum levels of immature platelets | Baseline |
| Serum levels of ultrasensitive C-reactive protein (hs-CRP); | Avaliation of Serum levels of ultrasensitive C-reactive protein (hs-CRP) | Baseline |
| Serum levels of interleukin 6 | Evaluation of Serum levels of interleukin 6 | Baseline |
| Serum levels of Interleukin 1 | Evaluation of interleukin 1 | Baseline |
| Serum levels of P-Selectin | Evaluation of Serum levels of P-Selectin | Baseline |
| Serum levels of D-dimero | Evaluation of Serum levels of D-dimero | Baseline |
| Serum levels of Lipoprotein(a) (LPa) | Evaluation of Serum levels of Lipoprotein(a) (LPa) | Baseline |
| Serum levels of Glycated hemoglobin | Evaluation of Serum levels of Glycated hemoglobin | Baseline |
| Serum levels of coagulogram | Evaluation of Serum levels of coagulogram | Baseline |
| Serum levels of Fibrinogen | Evaluation of Serum levels of Fibrinogen | Baseline |
| Serum levels of cholesterol ester transfer proteins | Evaluation of Serum levels of cholesterol ester transfer proteins | Baseline |
| Serum levels of blood count with platelets | Evaluation of Serum levels of blood count with platelets | Baseline |
| Subgroup Analysis- Diabetes mellitus | Diabetes mellitus (presence or not) | Baseline and 14 days |
| Subgroup Analysis-Glomerular filtration rate | Glomerular filtration rate (CKD EPI) (< 60ml/min/m2 or ≥ 60 ml/min/m2) | Baseline and 14 days |
| Subgroup Analysis- BDI | Body Mass Index (<30 or ≥ 30 kg/m2) | Baseline and 14 days |
| Subgroup Analysis- Smoking | Current smoking (yes or no) | Baseline and 14 days |
| 6322957 | Background | Zacharski LR, Henderson WG, Rickles FR, Forman WB, Cornell CJ Jr, Forcier RJ, Edwards RL, Headley E, Kim SH, O'Donnell JF, et al. Effect of warfarin anticoagulation on survival in carcinoma of the lung, colon, head and neck, and prostate. Final report of VA Cooperative Study #75. Cancer. 1984 May 15;53(10):2046-52. doi: 10.1002/1097-0142(19840515)53:103.0.co;2-f. |
| 29106448 | Background | Ek L, Gezelius E, Bergman B, Bendahl PO, Anderson H, Sundberg J, Wallberg M, Falkmer U, Verma S, Belting M; Swedish Lung Cancer Study Group (SLUSG). Randomized phase III trial of low-molecular-weight heparin enoxaparin in addition to standard treatment in small-cell lung cancer: the RASTEN trial. Ann Oncol. 2018 Feb 1;29(2):398-404. doi: 10.1093/annonc/mdx716. |
| 26700124 | Background | Macbeth F, Noble S, Evans J, Ahmed S, Cohen D, Hood K, Knoyle D, Linnane S, Longo M, Moore B, Woll PJ, Appel W, Dickson J, Ferry D, Brammer C, Griffiths G. Randomized Phase III Trial of Standard Therapy Plus Low Molecular Weight Heparin in Patients With Lung Cancer: FRAGMATIC Trial. J Clin Oncol. 2016 Feb 10;34(5):488-94. doi: 10.1200/JCO.2015.64.0268. Epub 2015 Dec 23. |
| 15304029 | Background | Altinbas M, Coskun HS, Er O, Ozkan M, Eser B, Unal A, Cetin M, Soyuer S. A randomized clinical trial of combination chemotherapy with and without low-molecular-weight heparin in small cell lung cancer. J Thromb Haemost. 2004 Aug;2(8):1266-71. doi: 10.1111/j.1538-7836.2004.00871.x. |
| 32776968 | Background | Meikle CK, Meisler AJ, Bird CM, Jeffries JA, Azeem N, Garg P, Crawford EL, Kelly CA, Gao TZ, Wuescher LM, Willey JC, Worth RG. Platelet-T cell aggregates in lung cancer patients: Implications for thrombosis. PLoS One. 2020 Aug 10;15(8):e0236966. doi: 10.1371/journal.pone.0236966. eCollection 2020. |
| 28818202 | Background | Navi BB, Reiner AS, Kamel H, Iadecola C, Okin PM, Elkind MSV, Panageas KS, DeAngelis LM. Risk of Arterial Thromboembolism in Patients With Cancer. J Am Coll Cardiol. 2017 Aug 22;70(8):926-938. doi: 10.1016/j.jacc.2017.06.047. |
| 20502945 | Background | Mangalpally KK, Siqueiros-Garcia A, Vaduganathan M, Dong JF, Kleiman NS, Guthikonda S. Platelet activation patterns in platelet size sub-populations: differential responses to aspirin in vitro. J Thromb Thrombolysis. 2010 Oct;30(3):251-62. doi: 10.1007/s11239-010-0489-x. |
| 10737280 | Background | Heit JA, Silverstein MD, Mohr DN, Petterson TM, O'Fallon WM, Melton LJ 3rd. Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study. Arch Intern Med. 2000 Mar 27;160(6):809-15. doi: 10.1001/archinte.160.6.809. |
| 15701913 | Background | Blom JW, Doggen CJ, Osanto S, Rosendaal FR. Malignancies, prothrombotic mutations, and the risk of venous thrombosis. JAMA. 2005 Feb 9;293(6):715-22. doi: 10.1001/jama.293.6.715. |
| 30708967 | Background | Metharom P, Falasca M, Berndt MC. The History of Armand Trousseau and Cancer-Associated Thrombosis. Cancers (Basel). 2019 Jan 31;11(2):158. doi: 10.3390/cancers11020158. |
| 24608188 | Background | Marks MA, Engels EA. Venous thromboembolism and cancer risk among elderly adults in the United States. Cancer Epidemiol Biomarkers Prev. 2014 May;23(5):774-83. doi: 10.1158/1055-9965.EPI-13-1138. Epub 2014 Mar 8. |
| D009930 |
| Organic Chemicals |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |