Background Early termination of clinical trials due to low recruitment represents an understudied challenge for clinical research. We aimed to describe characteristics of cardiovascular trials ...terminated because of low recruitment and identify the major predictors of such early termination. Methods We reviewed all cardiovascular clinical trials (7,042 studies) registered in ClinicalTrials.gov from February 29, 2000, to January 17, 2013, and assessed information about trials that were completed and those that were terminated early. Logistic regression models were developed to identify independent predictors of early termination due to low recruitment. Results Our search strategy identified 6,279 cardiovascular clinical trials, of which 684 (10.9%) were terminated prematurely. Of these halted trials, the main reason for termination was lower than expected recruitment (278 trials; 53.6%). When comparing trials that terminated early because of low recruitment with those that were completed, we found that studies funded by the National Institutes of Health or other US federal agencies (odds ratio OR 0.35, 95% confidence interval CI 0.14-0.89), studies of behavior/diet intervention (OR 0.35, 95% CI 0.19-0.65), and single-arm design studies (OR 0.57, 95% CI 0.42-0.78) were associated with a lower risk of early termination. University/hospital-funded (OR 1.52, 95% CI 1.10-2.10) and mixed-source–funded studies (OR 2.14, 95% CI 1.52-3.01) were associated with a higher likelihood of early termination due to lower than expected recruitment rates. Conclusions Low recruitment represents the main cause of early termination of cardiovascular clinical trials. Funding source, type of intervention, and study design are factors associated with early termination due to low recruitment and might be good targets for improving enrollment into cardiovascular clinical trials.
Translating evidence into clinical practice in the management of acute ischemic stroke (AIS) and transient ischemic attack (TIA) is challenging especially in low- and middle-income countries.
The aim ...of this study is to assess the effect of a multifaceted quality improvement intervention on adherence to evidence-based therapies for AIS and TIA patients care.
We designed a pragmatic, 2-arm cluster-randomized trial involving 36 clusters and 1624 patients from Brazil, Argentina, and Peru. Hospitals are randomized to receive a multifaceted quality improvement intervention (intervention group) or to routine care (control group). The BRIDGE Stroke multifaceted quality improvement intervention includes case management, reminders, health care providers’ educational materials (including treatment algorithms), interactive workshops, and audit and feedback reports. Primary outcome is a composite adherence score to AIS and TIA performance measures. Secondary outcomes include an “all or none” composite end point to performance measures, the individual components of the composite end points, and clinical outcomes at 90 days following admission (stroke recurrence, death, and disability measured by the modified Rankin scale).
The BRIDGE Stroke Trial is an international pragmatic evaluation of a multifaceted quality improvement intervention. If effective, this intervention could be potentially extended widely to improve the quality of care and outcomes of patients with AIS or TIA.
Recent research efforts on bariatric surgery have focused on metabolic and diabetes mellitus resolution. Randomized trials designed to assess the impact of bariatric surgery in patients with obesity ...and hypertension are needed.
In this randomized, single-center, nonblinded trial, we included patients with hypertension (using ≥2 medications at maximum doses or >2 at moderate doses) and a body mass index between 30.0 and 39.9 kg/m
. Patients were randomized to Roux-en-Y gastric bypass plus medical therapy or medical therapy alone. The primary end point was reduction of ≥30% of the total number of antihypertensive medications while maintaining systolic and diastolic blood pressure <140 mm Hg and 90 mm Hg, respectively, at 12 months.
We included 100 patients (70% female, mean age 43.8±9.2 years, mean body mass index 36.9±2.7 kg/m2), and 96% completed follow-up. Reduction of ≥30% of the total number of antihypertensive medications while maintaining controlled blood pressure occurred in 41 of 49 patients from the gastric bypass group (83.7%) compared with 6 of 47 patients (12.8%) from the control group with a rate ratio of 6.6 (95% confidence interval, 3.1-14.0;
<0.001). Remission of hypertension was present in 25 of 49 (51%) and 22 of 48 (45.8%) patients randomized to gastric bypass, considering office and 24-hour ambulatory blood pressure monitoring, respectively, whereas no patient submitted to medical therapy was free of antihypertensive drugs at 12 months. A post hoc analysis for the primary end point considering the SPRINT (Systolic Blood Pressure Intervention Trial) target reached consistent results, with a rate ratio of 3.8 (95% confidence interval, 1.4-10.6;
=0.005). Eleven patients (22.4%) from the gastric bypass group and none in the control group were able to achieve SPRINT levels without antihypertensives. Waist circumference, body mass index, fasting plasma glucose, glycohemoglobin, low-density lipoprotein cholesterol, triglycerides, high-sensitivity C-reactive protein, and 10-year Framingham risk score were lower in the gastric bypass than in the control group.
Bariatric surgery represents an effective strategy for blood pressure control in a broad population of patients with obesity and hypertension.
URL: https://clinicaltrials.gov. Unique identifier: NCT01784848.
Although Roux-en-Y gastric bypass (RYGB) results in significant weight loss and cardiometabolic risk factors improvements; there is no consensus whether limb lengths may influence these results.
To ...evaluate the correlations between the common limb length (CLL) and hypertension remission rate, cardiometabolic risk factors, and nutritional parameters after RYGB.
Private Hospital, Brazil.
GATEWAY is a randomized trial designed to evaluate the efficacy of RYGB on hypertension improvement and other cardiometabolic risk factors in patients with grade I and II obesity compared with medical therapy. The follow-up was 1 year. We measured the entire bowel in all patients and used a 150-cm alimentary limb and a 100-cm biliopancreatic limb. Univariate logistic regression was used to estimate the relationship between CLL and hypertension remission. Pearson and Spearman correlation were used to evaluate the correlation between the CLL and the percentage changes of cardiometabolic risk factors and nutritional parameters.
From 100 randomized patients, 45 were submitted to RYGB and completed the follow-up. Mean CLL was 466.3 ± 86.4 cm. Of patients, 55.6% from the RYGB group showed remission of hypertension. CLL length was not significantly associated with hypertension remission (odds ratio 95% confidence interval for 50 units increase in CLL: .97 .68; 1.38, P = .88). Consistently, we found no correlations between CLL and all changes in cardiometabolic risk factors and nutritional parameters.
In a proximal RYGB, CLL does not influence hypertension remission, cardiometabolic risk factors, and nutritional parameters.
Halofuginone (PJS-539) is an oral prolyl-tRNA synthetase inhibitor that has a potent in vitro activity against SARS-CoV-2 virus. The safety and efficacy of halofuginone in Covid-19 patients has not ...been studied.
We conducted a phase II, randomized, double-blind, placebo-controlled, dose ranging, safety and tolerability trial of halofuginone in symptomatic (≤ 7 days), mostly vaccinated, non-hospitalized adults with mild to moderate Covid-19. Patients were randomized in a 1:1:1 ratio to receive halofuginone 0.5mg, 1mg or placebo orally once daily for 10 days. The primary outcome was the decay rate of the SARS-CoV-2 viral load logarithmic curve within 10 days after randomization.
From September 25, 2021, to February 3, 2022, 153 patients were randomized. The mean decay rate in SARS-CoV-2 viral load log10 within 10 days was -3.75 (95% CI, -4.11; -3.19) in the placebo group, -3.83 (95% CI, -4.40; -2.27) in the halofuginone 0.5mg group and -4.13 (95% CI, -4.69; -3.57) in the halofuginone 1mg group, with no statistically significant difference in between placebo vs. halofuginone 0.5mg (mean difference -0.08; 95% CI -0.82 to 0.66, p = 0.96) and between placebo vs. halofuginone 1mg (mean difference -0.38; 95% CI, -1.11; 0.36, p = 0.41). There was no difference on bleeding episodes or serious adverse events at 28 days.
Among non-hospitalized adults with mild to moderate Covid-19 halofuginone treatment was safe and well tolerated but did not decrease SARS-CoV-2 viral load decay rate within 10 days.
To assess the effect of antisense therapy to block kallikrein-kinin pathway in COVID-19 patients.
Randomized, placebo-controlled, double blind, controlled trial enrolling hospitalized COVID-19 ...patients that required supplementary oxygen to sustain peripheral oxygen saturation. Key exclusion criteria included use of mechanical ventilation or vasopressors, and patients with more than 10 days since symptom onset or more than 48 h of oxygen use. Patients were randomized to either one subcutaneous dose of ISIS721744, an antisense that blocks prekallikrein, or placebo. The primary outcome was the number of days alive and free of oxygen support up to 15 days (DAFOR15). Secondary endpoints included organ failure score, need and duration of mechanical ventilation up to 15 days, and all-cause mortality at 30 days. Exploratory endpoints included physiological parameters, biomarkers, and quality of life.
From October 10, 2020, to December 09, 2020, 111 patients were randomized at thirteen sites in Brazil (56 to treatment and 55 to control group). Average age was 57.5 years, and most patients were male (68.5%). There were no significant differences in DAFOR15 between groups (5.9 ± 5.2 days for the intervention arm and 7.7 ± 5.1 for the control group; mean difference − 0.65, 95% confidence intervals from −2.95 to 1.36, p = 0.520).
Antisense therapy designed to block the kallikrein-kinin pathway did not demonstrate clinical benefits in increasing days-alive without respiratory support at 15 days in patients with COVID-19 during the first wave in 2020.
NCT04549922
•Abnormal activation of the kallikrein-kinin system has been hypothesized to be related to inflammation in COVID-19•Antisense therapy that blocks prekallikrein synthesis could potentially reduce inflammation in COVID-19 patients and improve outcomes.•In this randomized controlled trial, antisense therapy that blocks prekallikrein synthesis did not result in more days alive and free of oxygen support at 15 days.
Previous evidence suggests that acute treatment with statins reduce atherosclerotic complications, including periprocedural myocardial infarction, but currently, there are no large, adequately ...powered studies to define the effects of early, high-dose statins in patients with acute coronary syndrome (ACS) and planned invasive management.
The main goal of Statins Evaluation in Coronary procedUres and REvascularization (SECURE-PCI) Trial is to determine whether the early use of a loading dose of 80 mg of atorvastatin before an intended percutaneous coronary intervention followed by an additional dose of 80 mg 24 hours after the procedure will be able to reduce the rates of major cardiovascular events at 30 days in patients with an ACS.
The SECURE-PCI study is a pragmatic, multicenter, double-blind, placebo-controlled randomized trial planned to enroll around 4,200 patients in 58 different sites in Brazil. The primary outcome is the rate of major cardiovascular events at 30 days defined as a composite of all-cause mortality, nonfatal acute myocardial infarction, nonfatal stroke, and coronary revascularization.
The SECURE PCI is a large randomized trial testing a strategy of early, high-dose statin in patients with ACS and will provide important information about the acute treatment of this patient population.
Loading doses of atorvastatin did not show reduction on clinical outcomes in the overall population of patients with acute coronary syndrome (ACS) enrolled in the Statins Evaluation in Coronary ...Procedures and Revascularization (SECURE-PCI) trial, but a potential benefit was identified in patients who subsequently underwent percutaneous coronary intervention (PCI).
To determine whether periprocedural loading doses of atorvastatin are associated with decreased 30-day major adverse cardiovascular events (MACE) in patients with ACS undergoing PCI according to type of ACS and timing of atorvastatin administration before PCI.
Secondary analysis of a multicenter, double-blind, placebo-controlled, randomized clinical trial conducted at 53 sites that enrolled 4191 patients with ACS intended to be treated with PCI between April 18, 2012, and October 06, 2017.
Patients were randomized to 2 loading doses of 80 mg of atorvastatin or matching placebo before and 24 hours after a planned PCI. By protocol, all patients (regardless of treatment group) received 40 mg of atorvastatin for 30 days starting 24 hours after the second dose of study medication.
The primary outcome was MACE through 30 days, composed by all-cause mortality, myocardial infarction, stroke, and unplanned coronary revascularization. Cox regression models adjusting for key baseline characteristics were used to assess the association between atorvastatin and MACE in patients undergoing PCI.
From the overall trial population, 2710 (64.7%) underwent PCI (650 women 24.0%; mean SD age, 62 11.3 years). Loading atorvastatin was associated with reduced MACE at 30 days by 28% in the PCI group (adjusted hazard ratio HR, 0.72; 95% CI 0.54-0.97; P = .03). Loading dose of atorvastatin was administered less than 12 hours before PCI in 2548 patients (95.3%) (45.1% < 2 hours and 54.3% between 2 and 12 hours). There was no significant interaction between treatment effect and timing of study drug administration. The treatment effect of loading atorvastatin was more pronounced in patients with ST-segment elevation myocardial infarction than in patients with non-ST-segment elevation ACS (adjusted HR, 0.59; 95% CI, 0.38-0.92; P = .02; HR, 0.85; 95% CI, 0.58-1.27; P = .43, respectively).
In patients with ACS undergoing PCI, periprocedural loading doses of atorvastatin appeared to reduce the rate of MACE at 30 days, most clearly in patients with ST-segment elevation myocardial infarction. This beneficial effect seemed to be preserved and consistent, irrespective of the timing of atorvastatin administration, including within 2 hours before PCI.
clinicaltrials.gov Identifier: NCT01448642.
Assessing the Brazilian clinical practice in patients with acute coronary syndrome, in public and private hospitals to identify gaps in the incorporation of clinical interventions with proven ...benefit.
To develop a registry of patients diagnosed with acute coronary syndrome to assess demographics, morbidity, mortality, and standard practice in the care of this condition. Besides, to assess the prescription of evidence-based interventions such as aspirin, statins, beta blockers and reperfusion, among others.
Registry-type prospective observational study intended to document hospital clinical practices of acute coronary syndrome in public and private hospitals in Brazil. In addition, longitudinal follow-up will be held until discharge and measurement of mortality and occurrence of serious events at 30 days, 6 and 12 months.
The findings will be presented one year after the start of collection (September 2011), and consolidated after a meeting with the population to discuss the objectives sought.
The analysis of this multicenter registry will design a horizontal perspective for the treatment of patients suffering from cardiovascular disease in Brazil.
The ACCEPT registry was designed with the purpose of identifying the incorporation of evidence in the treatment of acute coronary syndrome. The objective of this analysis is to describe the ...antithrombotic therapy adopted in the treatment of patients undergoing primary percutaneous coronary intervention (PCI) in centers participating in this national project.
We evaluated the subgroup of patients undergoing primary PCI, measuring variables related to demographic characteristics as well as the prescription of evidence-based interventions, focusing on in-hospital and 6-month antithrombotic therapy.
From August 2010 to December 2011, 588 patients with mean age of 61.8±12.3 years were studied, 75.2% were males and 24.1% had diabetes mellitus. The dual antiplatelet therapy most commonly given was the combination of acetylsalicylic acid (ASA) and clopidogrel. Unfractionated heparin and enoxaparin were the predominant anticoagulation therapy during and after the procedure, respectively. When compared to in-hospital prescription, a significant decrease in the rate of patients using ASA (98.3% vs 93.9%; P<0.0001) and clopidogrel (95.4% vs 67.7%; P<0.0001) was observed at the 6-month follow-up.
In the ACCEPT registry, a high percentage of in hospital prescription of dual antiplatelet therapy was observed in patients undergoing primary PCI, notably the combination of ASA and clopidogrel, with an inadvertent reduction of clopidogrel at the 6-month follow-up, encouraging efforts to use evidence-based practices.
Farmacoterapia Antitrombótica Intra-Hospitalare aos Seis Meses após Intervenção Coronária Percutânea Primária: Análise do Registro da Prática Clínica em Síndrome Coronária Aguda (ACCEPT)
O registro ACCEPT foi idealizado com o propósito de identificar a incorporação de evidências no tratamento da síndrome coronária aguda. O objetivo da presente análise é descrever a terapia antitrombótica adotada no tratamento de pacientes submetidos a intervenção coronária percutânea (ICP) primária em centros participantes desse projeto nacional.
Avaliamos o subgrupo de pacientes submetidos a ICP primária, aferindo as variáveis relacionadas às características demográficas bem como à prescrição de intervenções baseadas em evidências, com enfoque na farmacoterapia antitrombótica hospitalar e aos 6 meses de seguimento.
No período de agosto de 2010 a dezembro de 2011 foram avaliados 588 pacientes com média de idade de 61,8±12,3 anos, 75,2% pertencentes ao sexo masculino e 24,1% portadores de diabetes melito. A terapia antiplaquetária dupla mais comumente administrada foi a associação ácido acetilsalicílico (AAS) e clopidogrel. Heparina não-fracionada e enoxaparina foram a terapêutica anticoagulante predominante durante e após o término do procedimento, respectivamente. Comparativamente à prescrição na fase intra-hospitalar, constatou-se, aos 6 meses de seguimento, queda significativa da taxa de pacientes em uso de AAS (98,3% vs. 93,9%; P<0,0001) e clopidogrel (95,4% vs. 67,7%; P<0,0001).
No registro ACCEPT, elevado porcentual de prescrição hospitalar de terapia antiplaquetária dupla foi observado em pacientes submetidos a ICP primária, notadamente da associação AAS e clopidogrel, com redução inadvertida do último aos 6 meses de seguimento, motivando esforços para adequação das práticas fundamentadas por evidências.
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