Hematological Parameters As Exclusion Criteria in Clinical Trials of Acute Coronary Syndrome

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3593-3593
Author(s):  
Ohad Oren ◽  
Douglas F. Beach
Keyword(s):  
Clinical Trials ◽  
Major Bleeding ◽  
Hematological Parameters ◽  
Active Bleeding ◽  
P Value ◽  
Exclusion Criteria ◽  
Coronary Syndrome ◽  
History Of ◽  
Risk For Bleeding ◽  
Or History

Abstract Background Non-cancerous medical conditions have a profound impact on the health of patients with malignancies. In individuals with lung cancer, the likelihood of death due to other causes is higher than that of the general population. It is therefore essential that patients with hematologic/oncologic diseases be effectively represented in non-oncologic clinical trials. Despite that truism, patients with cancer or with hematological impairments are typically excluded from clinical trials due to safety concerns. The frequency and degree to which hematological parameters or a diagnosis of cancer serve to exclude patients from practice-changing clinical studies in cardiology have yet to be determined. Whether studies that exclude patients based on such parameters have a lower incidence rate of major bleeding than those that do not is also unknown. Methods We focused on acute coronary syndrome (ACS). An investigation of the hematologic/oncologic exclusion profile of landmark studies of ACS was conducted. We searched The New England Journal of Medicine for all original research studies of ACS published between 2006 and 2016. Hematologic/oncologic exclusion criteria were reviewed. The nature of those parameters (laboratory value, disease state, medication use, clinical risk assessment) was analysed. The number of criteria per study as well as the percentage of participants excluded for meeting those criteria were recorded. The incidence of major bleeding (defined by TIMI bleeding criteria) among patients randomised into the interventional arms was compared between studies that excluded patients with particular derangements and those that did not. Results Thirty randomised clinical trials were found with a total number of patients of 235,981. Two thirds (20 out of 30) of the studies had at least one hematologic/oncologic exclusion criteria. The mean number of hematologic/oncologic exclusion criteria per study was 1.7. The most common exclusion parameter was laboratory-based. Ten studies (33.3%) specified cell count value as a cutoff for participation. Haemoglobin threshold (<10.0 mg/dl) was included in 4 studies (13.3%), while a platelet cutoff (<100k, >700k) was chosen in 9 publications (30%). Twelve studies (40%) issued active bleeding diathesis while six (20%) included "high-risk" for bleeding as exclusion criteria. Eight studies (26.6%) excluded patients who were chronically on oral anticoagulation. Six studies (20%) excluded patients with history of cancer. Seven studies (23.3%) had at least one subjective parameter in the list of exclusion criteria, such as "concerning lab abnormality", "high-risk" for bleeding, or "severe haematological disease". The aggregate incidence rate of major bleeding was significantly higher in studies that did not exclude for haemoglobin levels lower than 10 mg/dl compared with those that did (2.8% versus 1.6%, p value<0.05). Major bleeding rates were higher in studies that excluded patients on chronic anticoagulation than in studies that did not (3.6% versus 2.1%, p value<0.05). There was no significant difference in the incidence of major bleeding between studies that excluded patients with thrombocytopenia (platelets<100k), active bleeding or history of malignancy and studies that did not (Table 1). Not a single publication reported the fraction of patients excluded due to hematological impairments or history of cancer. Conclusions Hematological parameters as well as a medical history of a cancer commonly serve as exclusion criteria in studies of patients with ACS. Our analysis suggests that there may be a need for better standardization of exclusion criteria in studies in cardiovascular medicine, given that almost a quarter of high-quality studies of ACS include at least one inherently subjective parameter. The results provide support for uniformly setting severe anemia as exclusion criteria in studies of ACS until further data is available. Interestingly, enrolling patients with thrombocytopenia (platelets<100k), active bleeding or history of malignancy translated into similar rates of major bleeding, suggesting that some patient populations may be unnecessarily restricted from participating in clinical trials. Lastly, data pertaining to the subgroups of patients who were excluded based on those impairments is lacking and should be reported in future studies. Disclosures No relevant conflicts of interest to declare.

Prognosis in patients with prior myocardial infarction and PEGASUS-TIMI 54 criteria in the CLARIFY registry

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S Biscaglia ◽  
G Campo ◽  
K Fox ◽  
J.C Tardif ◽  
M Tendera ◽  
...  
Keyword(s):  
High Risk ◽  
Major Bleeding ◽  
Artery Bypass ◽  
Real Life ◽  
Prolonged Treatment ◽  
Funding Source ◽  
Inclusion Criteria ◽  
Private Company ◽  
Exclusion Criteria ◽  
Coronary Syndrome

Abstract Background/Introduction The PEGASUS-TIMI 54 trial showed that prolonged treatment with ticagrelor reduces the cumulative occurrence of ischemic adverse events. CLARIFY is the biggest real life registry on chronic coronary syndrome. Purpose - To evaluate the percentage of patients eligible for long-term ticagrelor therapy in the CLARIFY registry. – To compare the outcome of this subgroup of patients with those with PEGASUS exclusion criteria or without PEGASUS inclusion criteria. Methods Within the CLARIFY population, we selected post MI patients and we excluded those with missing info (post MI evaluable population). Then, we divided patients into 3 groups: excluded (meeting PEGASUS exclusion criteria, namely use of P2Y12 receptor antagonists or chronic oral anticoagulant, any stroke, coronary-artery bypass grafting in the past 5 years); eligible (meeting PEGASUS high-risk inclusion criteria, namely age≥65 years; diabetes; multivessel disease; creatinine clearance &lt;60 ml/min) and ineligible (not meeting PEGASUS high-risk inclusion criteria). We therefore compared the ischemic (CV death, MI and stroke) and bleeding (major bleeding) outcome of the 3 groups adjusting for age, sex, smoking and geographical region. Results Among the 11811 post-MI evaluable patients, 4706 (39.8%) were included in the eligible group, 5715 (48.4%) in the excluded group, and 1390 in the ineligible group (11.8%). Both the ischemic and bleeding endpoints were significantly different among the 3 groups with the excluded patients with the worst and ineligible patients with the best outcome (see table). The same trend was shown for CV death, while the occurrence of MI was not significantly different among the 3 groups. In the eligible group, the ratio between ischemic and bleeding events was 6:1, whereas between CV death and major bleeding was 3.5:1. Conclusions Around 40% of CLARIFY post-MI patients could benefit from prolonged ticagrelor therapy. In this group of patients, ischemic risk seems to be higher than the bleeding one. Ischemic & bleeding risk in the 3 groups Funding Acknowledgement Type of funding source: Private company. Main funding source(s): CLARIFY registry was funded by Servier

scholarly journals Metabolic Risk Factors and Outcomes in Acute Coronary Syndrome

2020 ◽  
pp. 46-50
Author(s):  
Ritu Attri ◽  
Harsimran Kaur ◽  
Raminderpal Singh Sibia ◽  
Mandip Singh Bhatia
Keyword(s):  
Risk Factors ◽  
Acute Coronary Syndrome ◽  
Positive Family History ◽  
Developed Countries ◽  
P Value ◽  
Health Crisis ◽  
Female Ratio ◽  
Medical College ◽  
Coronary Syndrome ◽  
History Of

Introduction: CAD is the most common cause of mortality in India. It is a common multifarious public health crisis today and a leading cause of morbidity and mortality in both developing and developed countries. Hence, understanding the predominant risk factors among the Indian population is important. Materials and Methods: This was a hospital based age and sex matched case control study, carried out at Government Medical College and Rajindra Hospital Patiala. A total of 100 patients of Acute coronary syndrome were studied. Patients and controls were enquired about  the presence of cardiometabolic risk factors and the significance of association of these risk factors with the occurrence of Acute coronary syndrome was given by p value of  <0.05. Results: Majority of the cases were in the age group 61-70 years (32%) with male to female ratio  of 1.25:1. Significant association was found between ACS and risk factors like smoking, positive family history of IHD, hypertension, diabetes, dyslipidemia, waist hip ratio and body mass index. Overall, most common outcome of ACS in the present study was NSTEMI (45%) followed by STEMI (35%) followed by Unstable angina (20%). Conclusion: Significant association was found between smoking and occurrence of STEMI and significant association was found between Hypertension and occurrence of NSTEMI.

6072Risk of stroke in hypertensive patients with atrial fibrillation treated with oral anticoagulants

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
R E Harskamp ◽  
W A M Lucassen ◽  
R D Lopes ◽  
H C Van Weert
Keyword(s):  
Atrial Fibrillation ◽  
Blood Pressure ◽  
Vitamin K ◽  
Major Bleeding ◽  
Oral Anticoagulants ◽  
Haemorrhagic Stroke ◽  
Uncontrolled Hypertension ◽  
P Value ◽  
Systemic Embolism ◽  
History Of

Abstract Background Hypertension is common in patients with atrial fibrillation (AF) and carries an additional risk for complications, most notably stroke and bleeding. We assessed the history of hypertension, level of blood pressure control, and an interaction with the choice of oral anticoagulants on clinical outcomes. Purpose To gain insights into the risks of hypertension in the setting of AF and explore possible interactions with the safety and efficacy of non-vitamin K oral anticoagulants (NOACs) versus vitamin K antagonists (VKAs). Methods We performed a systematic review and meta-analysis of studies that randomised patients to NOACs or VKAs and reported outcomes stratified by presence of hypertension. Collected outcomes included: ischaemic stroke or systemic embolism (SE), death from any cause, hemorrhagic stroke, major bleeding, and intracranial hemorrhage. Log adjusted hazard ratios (HR) and corresponding standard error were calculated, and HRs were compared using Mantel-Haenszel random effects. Quality of the evidence was assessed with Cochrane risk of bias tool. Results Five high-quality studies were eligible, including 71,602 participants who received NOACs (apixaban, dabigatran, edoxaban, rivaroxaban) or VKAs, with median follow-up of 1.8–2.8 years. 89.2% of participants had a history of hypertension. Compared with patients without hypertension, those with controlled and uncontrolled hypertension had higher risk for stroke/SE (HR: 1.21 [1.04–1.41] and HR: 1.50 [1.12–2.01], respectively) and haemorrhagic stroke (HR: 1.78 [1.06, 3.00] and HR: 1.66 [0.99–4.01], respectively). On a continuous scale, the risk of stroke increased 7% per 10mmHg increase in systolic blood pressure. As shown in the Table, no interactions were found between hypertension status and the efficacy or safety of NOACs versus VKAs. Table 1. Interaction of presence of hypertension on the comparative efficacy and safety of NOAC versus VKA Hypertension (n=63,869) No hypertension (n=7,733) P-value (int) Adjusted HR, 95% CI Adjusted HR, 95% CI Stroke or systemic embolism 080, 0.72–0.89 0.79, 0.53–1.19 0.98 Haemorrhagic stroke 0.55, 0.41–0.74 0.24, 0.04–1.37 0.36 Death from any cause 0.91, 0.84–0.98 0.89, 0.76–1.04 0.82 Major bleeding 0.90, 0.76–1.07 0.84, 0.69–1.01 0.57 Intracranial haemorrhage 0.41, 0.24-.068 0.48, 0.14–1.69 0.81 Major or clinically relevant non-major bleed 0.90, 0.68–1.18 0.91, 0.55–1.53 0.96 Conclusions Adequate blood pressure management is vital to optimally reduce the risk of stroke in patients with atrial fibrillation. The benefits of NOACs over VKAs, also apply to patients with elevated blood pressure.

Developments in Oral Antiplatelet Agents for the Treatment of Acute Coronary Syndromes

2015 ◽  
Vol 29 (3) ◽  
pp. 239-249 ◽  
Author(s):  
David S. Roffman
Keyword(s):  
Clinical Trials ◽  
Major Bleeding ◽  
Antiplatelet Agent ◽  
Antiplatelet Agents ◽  
Clinical History ◽  
Bleeding Risk ◽  
Phase Iii ◽  
Coronary Syndrome ◽  
Phase Iii Clinical Trials ◽  
Increased Risk

A review of the literature was conducted for clinical trials evaluating the antiplatelet P2Y12 receptor antagonists, clopidogrel, prasugrel, and ticagrelor, as well as the guidelines for the management of acute coronary syndrome (ACS) or myocardial infarction. Clinical guidelines recommend that patients with ACS be treated with dual oral antiplatelet therapy of aspirin plus clopidogrel, prasugrel, or ticagrelor. The selection of an appropriate antiplatelet agent depends on the treatment approach and a patient’s bleeding risk and clinical history. With respect to antiplatelet activity, prasugrel and ticagrelor demonstrate greater potency and less interpatient variability than clopidogrel. In phase III clinical trials, prasugrel and ticagrelor reduced the incidence of ischemic events in patients with ACS compared with clopidogrel. Ticagrelor and clopidogrel were associated with a similar risk of major bleeding, whereas patients receiving prasugrel had an increased risk of major bleeding versus those receiving clopidogrel. Pharmacists can provide guidance on the appropriate use of antiplatelet agents as well as the use of concomitant medications, while being vigilant for any potential drug interactions.

Clinical Outcome of Patients with Venous Thromboembolism and Recent Major Bleeding: Findings from a Prospective Registry (RIETE).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 708-708
Author(s):  
Manuel Monreal ◽  
José Nieto ◽  
Ana de Tuesta ◽  
Pablo Marchena ◽  
Gregorio Tiberio ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Venous Thromboembolism ◽  
Clinical Outcome ◽  
Clinical Outcomes ◽  
Major Bleeding ◽  
Bleeding Complications ◽  
P Value ◽  
Minor Bleeding ◽  
Fatal Bleeding ◽  
Overall Mortality

Abstract Introduction Patients who have experienced a recent major bleeding episode are usually excluded from clinical trials of venous thromboembolism (VTE) treatment. Therefore, recommendations based on evidence from clinical trials of VTE treatment may not be optimal for these patients. The Registro Informatizado de la Enfermedad TromboEmbólica (RIETE), initiated in March 2001, is a multicenter, observational registry gathering data on VTE treatment practices and clinical outcomes in patients with objectively confirmed, symptomatic, acute VTE. The aim of this analysis was to study outcomes in patients with VTE who had experienced major bleeding <30 days prior to VTE diagnosis. Methods Patients with objectively confirmed symptomatic acute VTE are consecutively enrolled into the RIETE registry. Patients are excluded if they are participating in a therapeutic clinical trial or not available for 3-months follow-up. Patient characteristics, details of antithrombotic therapy, and clinical outcomes at 3-months are recorded. Results Of 6361 patients enrolled up to January 2004, 170 (2.7%) had experienced recent major bleeding prior to VTE diagnosis: 69 (40.6%) gastrointestinal tract; 60 (35.3%) intracranial; 41 (24.1%) other. More patients with recent major bleeding had cancer compared with those without recent major bleeding (26.4% vs 20.4%, respectively; p=0.05). More patients who experienced recent major bleeding had undergone surgery <2 months prior to enrollment or had immobility ≥4 days. The incidences of recurrent PE and minor, major, and fatal bleeding complications were also higher in patients who had experienced recent major bleeding (table 1). Patients with recent major bleeding and cancer had an increased incidence of major bleeding compared to those without cancer (20.0% vs. 2.4%, respectively; OR 10.0; 95% CI 2.3–50.0; p<0.001); 11.0% of patients who had recent major bleeding prior to VTE diagnosis and cancer experienced fatal PE compared with none in patients who had recent major bleeding but without cancer (OR 4.1; 95% CI 4.98–17; p<0.05). Conclusion Patients with VTE and recent major bleeding prior to VTE diagnosis (2.7% of total enrolled patients) had poorer clinical outcomes, in terms of bleeding complications, fatal PE and overall mortality compared with those who had not experienced recent major bleeding. In patients who had recent major bleeding prior to VTE diagnosis, those with cancer had a poorer clinical outcome than those without cancer. Table 1. Clinical outcome of enrolled patients 3-month outcome Recent major bleeding No recent major bleeding OR (95% CI) p value n (%) n=170 n=6191 Fatal bleeding 7 (4.1) 41 (0.6) 6.4 (2.6-15) <0.001 Major bleeding 12 (7.1) 146 (2.3) 3.1 (1.6-5.9) 0.001 Minor bleeding 12 (7.1) 172 (2.8) 2.6 (1.4-5.0) <0.005 Fatal (initial) PE 1 (0.6) 14 (0.2) 2.6 (0.2-19) NS Fatal (recurrent) PE 4 (2.4) 33 (0.5) 4.5 (1.3-14) <0.05 Recurrent VTE 8 (4.7) 184 (2.9) 1.6 (0.7-3.4) NS Overall mortality 25 (15.0) 479 (7.7) 2.1 (1.3-3.2) <0.005

scholarly journals Fragmented QRS Complex as a Predictor of Multivessel Disease in Acute Coronary Syndrome

2017 ◽  
pp. 130-6
Author(s):  
Idar Mappangara ◽  
Abdul Hakim Alkatiri ◽  
Stefan Hendyanto
Keyword(s):  
Acute Coronary Syndrome ◽  
Logistic Regression ◽  
Cross Sectional Study ◽  
Multivessel Disease ◽  
P Value ◽  
Qrs Complex ◽  
Cross Sectional ◽  
Coronary Syndrome ◽  
Fragmented Qrs ◽  
History Of

Background: The incidence of multivessel disease in acute coronary syndrome (ACS) is expected to be identified as early as possible in order to perform optimal management. The presence of multivessel disease can lead to ischemia or myocardial infarction. Fragmented QRS complex (fQRS) is a new electrocardiography (ECG) parameter that has been proven to be caused by ischemia or myocardial infarction.Methods: A cross-sectional study. Patients with ACS that admitted at Dr. Wahidin Sudirohusodo Makassar since December 2014 - March 2015 who are eligible were enrolled in this study.Presence of fQRS evaluated on first 12-lead ECG at hospital admission. Presence of multivessel disease based on coronary angiography. Data were analyzed by logistic regression. Data was significant if the p-value<0.05.Results: There are 63 subjects (56 men and 7 women) included in this study. Older age, history of ACS before, presence of dyslipidemia, and presence of fQRS were significantly more often in group with multivessel disease. After analyzed with logistic regression, the fQRS was the only significant predictor of multivessel disease with p value 0.003 and odds ratio 13.28.Conclusion: Presence of fQRS in the first 12-lead ECG when admitted to the hospital was an independent predictor of multivessel disease in patients with ACS.

4183New onset atrial fibrillation in acute coronary syndrome: early vs late onset

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
J Alves Guimaraes ◽  
F M Goncalves ◽  
S Borges ◽  
J J Monteiro ◽  
P S Mateus ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Acute Coronary Syndrome ◽  
Primary Endpoint ◽  
Major Bleeding ◽  
Late Onset ◽  
Prognostic Impact ◽  
Coronary Syndrome ◽  
History Of ◽  
Onset Atrial Fibrillation

Abstract Background The prognostic impact of the timing where new-onset Atrial Fibrillation (AF) occurs in Acute Coronary Syndrome (ACS) patients isn't well studied. Objective Evaluate the predictors and prognostic impact of early-onset AF (EAF) and late-onset AF (LAF) in ACS patients. Methods We analysed 17016 patients with ACS enrolled in a national multicenter registry from October 2010 to January 2019. Patients with history of valvular disease, valve replacement, AF present at hospital admission or those who died in the first 48 hours were excluded. EAF was defined as AF in the first 48 hours of hospitalization and LAF after 48 hours. The primary endpoint was a composite of death and readmission from cardiovascular causes at 1 year. Results The mean age was 65±13 years; 74% were males and 42% had STEMI). 324 (1.9%) had EAF and 344 (2.0%) had LAF. The predictors of EAF were age ≥75 years (OR 2.04, 95% CI 1.53–2.70, p<0.001); history of heart failure (OR 1.82, 95% CI 1.09–3.02, p=0.022), STEMI diagnosis (OR 2.74, 95% CI 2.06–3.61, p<0.001), admission Killip class (KK)≥2 (OR 2.70, 95% CI 1.98–3.69, p<0.001). The predictors of LAF were age ≥75 years (OR 3.15, 95% CI 2.36–4.19, p<0.001), history of stable angina (OR 1.42, 95% CI 1.06–1.90, p=0.018), cerebrovascular disease (OR 1.68, 95% CI 1.14–2.46, p=0.008), COPD (OR 2.33, 95% CI 1.58–3.44, p<0.001), STEMI diagnosis (OR 2.31, 95% CI 1.77–3.03, p<0.001), admission KK ≥2 (OR 2.06, 95% CI 1.54–2.76, p<0.001) and stress hyperglycemia (OR 1.54, 95% CI 1.15–2.05, p=0.003) In STEMI patients only those with LAF had higher symptoms time (245 (IQR 165–400) minutes vs 284 (IQR 200–425) min; p=0.02). During hospitalization, LAF patients had a worse prognosis with a higher rate of heart failure, re-infarction, stroke, major bleeding and death (Table 1). In the follow-up, in multivarite analysis, only LAF was a predictor of the primary endpoint (EAF: HR 0.79, 95% CI 0.50–1.25, p=0.314; LAF: HR 1.45, 95% CI 1.05–2.00, p<0.025). Complications during hospitalization No AF EAF LAF p Death 1.3 6.5 12.5 <0.001 Heart Failure 11.4 38.3 50.3 <0.001 Re-enfarction 1.0 0.9 3.5 <0.001 Stroke 0.5 0.9 3.8 <0.001 Major bleeding 1.3 4.3 4.1 <0.001 Kaplan Meier curve Conclusion Patients with EAF and LAF have different characteristics and outcomes with LAF patients having a worse in-hospital and long term prognosis.

The use of cardiovascular disease states as exclusion criteria in breast cancer trials: A 4-decade perspective.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18053-e18053
Author(s):  
Michal Oren ◽  
Ohad Oren ◽  
David M. Mintzer
Keyword(s):  
Breast Cancer ◽  
Cardiovascular Disease ◽  
Clinical Trials ◽  
Cardiac Disease ◽  
P Value ◽  
Published Data ◽  
Original Research ◽  
Breast Cancer Patients ◽  
Exclusion Criteria ◽  
Cardiac Condition

e18053 Background: At the time of diagnosis, patients with breast cancer have a higher prevalence of cardiovascular risk factors than the general population. It is likely that the prevalence of actual cardiac disease is also increased, although no published data is available to support this claim. Individuals with breast cancer who also have heart disease are typically disqualified from clinical trials. We attempted to define the evolution of cardiovascular exclusion criteria in clinical trials of breast cancer over the decades. Methods: We searched the NEJM for original research in “breast cancer” published from 01/1980 to 12/2016. We reviewed the nature of cardiovascular disease as exclusion parameters as well as trends over time. Results: 20 RCTs were analysed, 5 from each decade (total # of patients 21,231). Mean number of cardiac exclusion criteria per study increased over the decades (1980s: 0; 1990s: 0.2; 2000s: 1; 2010s: 7). The most common cardiac exclusion criteria were CHF and recent MI (35% and 25% of studies, respectively). Factors associated with a higher likelihood of having a cardiac exclusion criteria were source of funding (industry vs. university: 77.7% vs. 18.1%, P-value 0.005) and study’s country of origin (U.S versus non-U.S: 57.1% versus 16.6%, P-value 0.02). Prior to 2010, the complete list of exclusion criteria was available with the manuscript. From 2010, it became embedded within the study’s protocol file (and not printed). Cardiovascular AEs were infrequent (1980s: 0.02%; 1990s: 0%, 2000s: 0.08%; 2010: 0.29%). Before 2000, studies described the significant cardiac toxicity in the manuscript. After 2000, a comprehensive registry of AEs contained within supplementary files became the norm. Conclusions: The use of cardiovascular exclusion criteria in clinical trials in breast cancer has become common over the past decades. Currently, it is almost impossible for a woman to enter a trial with even a single cardiac condition. Given that a sizeable fraction of breast cancer patients has cardiac disease, consideration should be given to narrowing the scope of cardiac exclusion criteria to allow more patients to participate, while making the results of those trials more broadly generalisable.

scholarly journals How I treat patients with a history of heparin-induced thrombocytopenia

Blood ◽  
2016 ◽  
Vol 128 (3) ◽  
pp. 348-359 ◽  
Author(s):  
Theodore E. Warkentin ◽  
Julia A. M. Anderson
Keyword(s):  
Oral Anticoagulants ◽  
Chronic Hemodialysis ◽  
Short Term ◽  
Heparin Induced Thrombocytopenia ◽  
Coronary Syndrome ◽  
History Of ◽  
Minimum Interval ◽  
Direct Acting ◽  
Or History ◽  
Heparin Exposure

Abstract Heparin-induced thrombocytopenia (HIT) is a relatively common prothrombotic adverse drug reaction of unusual pathogenesis that features platelet-activating immunoglobulin G antibodies. The HIT immune response is remarkably transient, with heparin-dependent antibodies no longer detectable 40 to 100 days (median) after an episode of HIT, depending on the assay performed. Moreover, the minimum interval from an immunizing heparin exposure to the development of HIT is 5 days irrespective of the patient’s previous heparin exposure status or history of HIT. This means that short-term heparin reexposure can be safely performed if platelet-activating antibodies are no longer detectable at reexposure baseline and is recommended when heparin is the clear anticoagulant of choice, such as for cardiac or vascular surgery. The risk of recurrent HIT 1 to 2 weeks after heparin reexposure is ∼2% to 5% and is attributable to formation of delayed-onset (or autoimmune-like) HIT antibodies that activate platelets even in the absence of pharmacologic heparin. Some studies suggest that longer-term heparin reexposure (eg, for chronic hemodialysis) may also be reasonable. However, for other antithrombotic indications that involve patients with a history of HIT (eg, treatment of venous thromboembolism or acute coronary syndrome), preference should be given to non-heparin agents such as fondaparinux, danaparoid, argatroban, bivalirudin, or one of the new direct-acting oral anticoagulants as appropriate.

scholarly journals Characterizing Inclusion and Exclusion Criteria in Clinical Trials for CAR-T Cellular Therapy Among Adults with Hematologic Malignancies

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5819-5819
Author(s):  
Jordon Jaggers ◽  
Heidi D. Klepin ◽  
Tanya M. Wildes ◽  
Rebecca L. Olin ◽  
Andrew S. Artz ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Research Funding ◽  
Cellular Therapy ◽  
Phase 1 ◽  
Hematologic Malignancies ◽  
Advisory Board ◽  
Exclusion Criteria ◽  
Car T ◽  
History Of

Introduction: Clinical trial development and enrollment are pivotal to advancing cancer outcomes. Novel treatment modalities such as Chimeric Antigen Receptor (CAR) T-cell therapy is an intensive therapy that has altered the landscape of hematologic malignancy therapies, with several FDA approvals based on Phase I-II studies. Strict eligibility criteria are implemented to ensure safety of trial participants; however, these criteria can lead to barriers to patient enrollment, hinder the generalizability of the study, and result in a population of participants not representative of those who would benefit from therapy. The aim of this proposal is to characterize inclusion and exclusion criteria in clinical trials for CAR-T cellular therapy in adults with hematologic malignancies. Methods: The U.S. National Library of Medicine's Clinical Trial database of privately and publicly funded clinical studies was accessed June 2019 to assemble a list of studies with the following filters applied: hematologic, recruiting, not yet recruiting, not recruiting, active, completed, suspended, terminated studies, interventional studies, CAR, CAR T, chimeric antigen receptor, CAR NK, adult, older adult, early phase 1, phase 1, phase 2, phase 3. From this, 95 studies populated, 84 were utilized in this study and 11 studies excluded due to non-hematologic malignancy. Results: We analyzed 84 CAR-T clinical trials targeting multiple diseases (Table 1) including; acute lymphoblastic (n=7) and myeloid leukemia (n=2); lymphoma (n=6); multiple myeloma (n=40); multiple hematologic malignancies (n=27) and other (n=2). The majority of studies were phase 1 (n=47) or phase 1/2 (n=28). Upper age limit restrictions were in place for 53/84 (63%) of trials. Trials included the AYA population (n=5), ≤ age 65 (n=1), ≤ age 70 or 73 (n=26), ≤ age 75 or 78 (n=12), ≤ age 80 or 85 (n=9). Of the 84 trials, 65 (77%) had performance status inclusion criteria, most commonly was status ECOG 0-2 (n=23) and ECOG 0-1 (n=24). Patients were excluded for a history of a separate or concurrent malignancy in 52/84 (62%) trials, CNS disease was excluded in 45/84 (54%) trials and 70/84 (83%) clinical trials excluded infectious diseases; HIV (n=69) and Hepatitis B/C (n=64). Many studies had restrictions for impairment in organ function; renal impairment (n=66), cardiac deficits (n=67), and abnormal pulmonary function (n=44). Unique to CAR-T trials, 27/84 had restrictions in place for neurological disorders: epilepsy (n=15), history of brain injury (n=10), dementia (n=8), coordination/movement disorder (n=6), cerebellar disease (n=8), psychosis (n=7), paresis (n=6), history of stroke/aphasia (n=21), and active autoimmune or inflammatory disease of the central nervous system (n=3). Conclusion: CAR-T cellular therapy is a tremendous therapeutic advancement in the medical community. This study emphasizes, in detail, highly variable cross-study inclusion/exclusion criteria for early phase CAR-T studies. This new and promising therapy is actively being studied in a highly select group of patients and may not be generalizable to the older adult with hematologic malignancies due to non-uniform trial criteria. The applicability of this modality should be tempered by the understanding that CAR-T trials have overt age caps, ambiguous performance and comorbidity exclusions, and neurologic exclusions and play a role in limiting patient accessibility to novel clinical trial therapy. Confirmatory prospective and observational studies of CAR-T therapy in representative populations are a high priority. 1. Brudno JN, Kochenderfer JN. Toxicities of chimeric antigen receptor T cells: recognition and management. 2016 127:3321-3330. Doi: 10.1182/blood-2016-04-703751 2. Kim ES, Bruinooge SS, Roberts S, et al. Broadening Eligibility Criteria to Make Clinical Trials More Representative: American Society of Clinical Oncology and Friends of Cancer Research Joint Research Statement. J Clin Oncol. 2017;35(33):3737-3744. doi:10.1200/JCO.2017.73.7916 3. Unger JM, Cook E, Tai E, and Bleyer A. The Role of Clinical Trial Participation in Cancer Research: Barriers, Evidence, and Strategies. American Society of Clinical Oncology Educational Book. 2016; 36:185-198. Doi:10.1200/EDBK\_156686 Disclosures Wildes: Janssen: Research Funding; Carevive: Consultancy. Olin:Spectrum: Research Funding; Novartis: Research Funding. Artz:Miltenyi: Research Funding. Jaglowski:Unum Therapeutics Inc.: Research Funding; Kite: Consultancy, Other: advisory board, Research Funding; Juno: Consultancy, Other: advisory board; Novartis: Consultancy, Other: advisory board, Research Funding. William:Guidepoint Global: Consultancy; Defined Health: Consultancy; Techspert: Consultancy; Celgene Corporation: Consultancy; Kyowa Kirin, Inc.: Consultancy. Rosko:Vyxeos: Other: Travel support.

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