Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT02843243 |
| Other study ID # |
bova 1 protocol |
| Secondary ID |
|
| Status |
Terminated |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
December 2016 |
| Est. completion date |
March 31, 2019 |
Study information
| Verified date |
July 2021 |
| Source |
Azienda Ospedaliera Cosenza |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
A risk stratification in hemodynamically stable patients with acute pulmonary embolism (PE)
is deemed necessary to guide patient management. With the aim to improve the positive
predictive value (PPV) for PE-related adverse events in in normotensive patients, a number of
scores combining multiple risk-factors have been published. In addition, an algorithm for the
risk-stratification of patients with PE has been proposed by the European society of
cardiology. None but one of these scores underwent external and prospective validation. The
aim of this study is to externally and prospectively validate the PPV for PE-related adverse
events of the Bova score and modified FAST score in a large multicenter cohort.
Description:
A risk stratification in hemodynamically stable patients with acute pulmonary embolism (PE)
is deemed necessary to guide patient management. Right ventricular dysfunction (RVD),
identified by echocardiography or computed tomographic angiography (CT), and cardiac
biomarkers are well recognized risk factors for adverse events in normotensive patients with
PE. However, neither of them, as a single prognostic criterion, have a sufficient positive
predictive value (PPV) for PE-related adverse events to guide therapeutic decisions. The
PEITHO trial showed that, in normotensive patients with RVD and abnormal cardiac troponin,
death or hemodynamic decompensation occurred significantly less in those treated with
tenecteplase plus heparin than in those who received heparin plus placebo. However the risk
of major hemorrhage and stroke was significantly increased in the tecneplase group. These
results were obtained in a group of patients with an absolute rate of PE-related adverse
events of about 6%. If the same relative reduction in the risk of PE-related outcomes
observed in the PEITHO trial could be achieved in a group of patients with a higher absolute
risk of PE-related events, this might change the risk to benefit ratio of primary reperfusion
therapy in PE. With the aim to improve the PPV for PE-related adverse events in in
normotensive patients, a number of scores combining multiple risk-factors have been
published. In addition, an algorithm for the risk-stratification of patients with PE has been
proposed by the European society of cardiology. None but one of these scores underwent
external and prospective validation. Aim of the study The aim of this study is to externally
and prospectively validate the PPV for PE-related adverse events of the Bova score, modified
FAST score and ESC algorithm in a large multicenter cohort.
Methods. This will be a multicenter, prospective, observational study. Consecutive patients
aged 18 years or older with PE and hemodynamic stability (that is, SBP 90 mm Hg or more) will
be evaluated as a part of usual clinical practice. This study does not dictate diagnostic
interventions nor affects clinical or therapeutic decisions of the participant centers. For
each patient, anonymous information will be collected on simplified Pulmonary Embolism
Severity Index (sPESI), RVD on echocardiography and CT, Troponin I, levels of lactates in the
arterial blood, and presence of syncope at presentation. RVD will be diagnosed with the
echocardiography in the presence of one of the following: Right ventricular end-diastolic
diameter (RVEDD) > 30 mm (parasternal long-axis or short-axis view), Right/left ventricular
end-diastolic diameter (RVEDD/LVEDD) >0.9 (apical or subcostal 4-chamber view), Right
ventricular free wall hypokinesis from any view, Tricuspid systolic velocity > 2.6 m/s from
the apical or subcostal 4-CH view, parasternal short-axis view. RVD diagnosis with the CT
will require a RV/LV diameter ratio greater than 1.0 on axial CT images. Cardiac troponin
test will be considered positive in case of levels of troponin higher than higher than the
cut-off of the manufacturer. Plasma lactate will be assessed in arterial blood samples.
Values ≥ 2 mmol/L (18 mg/dL) will be considered abnormal. This evaluation should be ideally
completed within 6 hours from the hospital admission. The primary outcome of the study will
be adverse events PE-related within 30 days from the hospital admission. In a sensitivity
analysis we will explore the same outcome at 7 days. PE-relate adverse events will be defined
as: PE-related death or haemodynamic collapse. PE will be considered the cause of death if
there will be objective documentation or in case of unexplained death and PE not confidently
ruled out. Haemodynamic collapse will be defined as one of the following conditions: SBP < 90
mmHg necessitating catecholamine administration; mechanical ventilation; cardiopulmonary
resuscitation.
Secondary outcomes of interest will be all-cause mortality at 30 days; PE-related death at 30
days; confirmed symptomatic PE recurrence; duration of hospitalization in patients with low
and intermediate-low risk compared with patients with intermediate-high risk. Recurrent PE
will be confirmed either by the presence of a new intraluminal filling defect, or by a new
perfusion scan defect involving > 75% of a lung segment. PE-related adverse events, recurrent
PE and all-cause mortality should be evaluated, for each participant center, by a physician
not involved in the study.
Statistical analysis The three-level of Bova score will be dichotomized (low- and
intermediate-low-risk versus intermediate-high-risk). Receiver operating characteristic (ROC)
curve analysis will be performed to determine the area under the curve (AUC) of the scores
(absolute points) with regard to study outcomes. Prognostic performance of the scores will be
evaluated by calculation of sensitivity, specificity, positive predictive value (PPV) and
negative predictive value (NPV), and positive and negative likelihood ratios.
Sample size Based on previous studies a sample size of about 500 patients should be adequate
for the purpose of the study. After the first 300 patients an interim analysis will be
performed to more precisely establish the number of patients needed.
