Paul den Exter for the Vesta Study Investigators

Transcription

1 Efficacy and safety of outpatient treatment based on the Hestia clinical decision rule with or without NT-proBNP testing in patients with acute pulmonary embolism: a randomized clinical trial Am J Respir Crit Care Med. 2016;194: Paul den Exter for the Vesta Study Investigators Department of Thrombosis and Hemostasis LUMC Leiden

2 Conflict of Interest Disclosure Form In accordance with the rules of the Health Care Inspectorate (IGZ) Name: MVHuisman Affiliation: LUMC Leiden I have no potential conflict of interest to report [please delete the checkboxes to the left that aren t applicable, then delete this yellow text box] Type of affiliation / financial interest Name of commercial company Receipt of grants/research supports: Receipt of honoraria or consultation fees: Participation in a company sponsored speaker s bureau: Stock shareholder: Other support (please specify): Scientific advisory board

3 Declarations Menno Huisman No pharma declaration for this study Supported in part by a grant of the Gratama foundation

4 Introduction Outpatient treatment has become routine practice for DVT based on high level evidence Recent studies have indicated that selected patients with acute PE can be safely treated as outpatients as well Uncertain which method to use to select low-risk PE patients who can safely be treated at home

5 Vesta: rationale Hestia study 1 : Outpatient treatment in 297 PE patients selected by the Hestia criteria Mortality 1.0% Recurrent VTE: 2.0% Major bleeding: 0.7% Home study 2 : Outpatient treatment in 152 PE patients selected with clinical criteria combined with NT-proBNP testing (<500ng/L): Mortality: 0% Recurrent VTE: 0% Major bleeding: 0% 1. Zondag, JTH 2011; 9(8): Agterof, JTH 2010; 8(6):1235-4

6 Vesta study objectives 1. To assess whether the Hestia clinical decision rule alone is as safe as the Hestia rule combined with NT-pro BNP testing to select PE patients for outpatient treatment 2. To validate the Hestia clinical decision rule

7 Vesta study design Randomized, non-inferiority open label clinical trial (Netherlands Trial Register identifier NTR2603) Setting: 2 academic and 15 non-academic hospitals in the Netherlands between

8 Patients Aged 18 years or over Acute, symptomatic, objectively proven (recurrent) PE Life expectancy > 3 months Eligible for outpatient treatment according to the Hestia clinical decision rule Willing and able to give informed consent

9 Hestia clinical decision rule Hemodynamically unstable Thrombolysis/embolectomy necessary Need for i.v. pain medication Oxygen needed to keep O2 saturation > 90% PE diagnosed during therapeutic anticoagulation Active bleeding or high risk for bleeding Documented history of HIT Creatinine clearance < 30 ml/min Uncontrolled hypertension Pregnancy Medical/social reason for treatment in the hospital? If one or more items are present, the patient can not be treated at home

10 Interventions Arm A: NTproBNP testing NTproBNP >500 In hospital treatment Hestia criteria met NTproBNP <500 Direct discharge Arm B: Direct discharge Blood storage for post-hoc NTproBNP testing Randomization

11 Vesta Primary and secondary endpoints Primary endpoint: 30 day adverse outcome defined as: PE- or bleeding-related mortality, cardiopulmonary resuscitation or ICU admission Secondary endpoints: Adjudicated recurrent VTE at 3 months Adjudicated major bleeding at 3 months Adjudicated all-cause mortality at 3 months Sample size: 530 patients required to demonstrate noninferiority between groups, non-inferiority margin: 3.4%, power: 80%

12 Flow of patients Assessed for eligibility (n=1102)) Enrollment Excluded: (n=552) Randomized (n=550) NT-proBNP testing Lost to follow-up (n=0) Allocation Follow-Up n=550 Direct discharge Lost to follow-up (n=0)

13 Baseline charecteristics NT-proBNP Direct discharge Characteristic (N=275) (N=275) Age (mean ± SD) 55 (15) 53 (15) Age > 60 (n, %) 108 (39.3) 99 (36.0) Male sex (n, %) 145 (52.7) 152 (55.3) BMI (kg/m2, mean ± SD) 27.0 (4.6) 27.7 (5.2) VTE Risk factors Immobilization or recent surgery (n, %) 33 (12.2) 39 (14.4) Previous PE (n, %) 41 (15.1) 45 (16.6) Previous DVT (n, %) 30 (11.0) 28 (10.3) Active Malignancy (n, %) 23 (8.5) 14 (5.2) Estrogen use (n, %) 50 (18.4) 45 (16.6) Comorbidities COPD with therapy (n, %) 9 (3.3) 14 (5.2) Heart failure with therapy (n, %) 3 (1.1) 2 (0.7)

14 NT-proBNP assessment Hestia criteria met Arm A: NTproBNP testing N=275 NTproBNP >500 NTproBNP <500 N=34 (12%) N=241 (88%) Hospital Arm B: Direct discharge N=275 NTproBNP >500 NTproBNP <500 N=23 (8%) N=252 (92%) Home

15 Primary endpoint Direct discharge group: 3 patients: 1.1%; 95% CI: % NT-proBNP group: 0 patients: 0%; 95% CI: 0-1.3% Absolute difference 1.1 %: 95% CI: -0.5% - 3.2% None of the patients who experienced the primary endpoint had elevated NT-proBNP levels at baseline

16 Primary and secondary endpoints NT-proBNP Direct discharge Outcome (n=275) (n=275) Primary endpoint* at day (1.1%) PE related mortality 0 1 (0.36%) ICU admission 0 2 (0.73%) Recurrent VTE at 3 months 2 (0.73%) 3 (1.1%) DVT 1 (0.36%) 1 (0.46%) Recurrent PE 1 (0.36%) 2 (0.73%) Major bleeding at 3 months 1 (0.36%) 3 (1.1%) All-cause mortality at 3 months 4 (1.5%) 3 (1.1%)

17 Conclusions Outpatient treatment of acute PE patients selected by the Hestia clinical decision rule alone is safe Additional prognostic assessment based on NT-proBNP levels did not affect the prognosis

18 Conclusions Outpatient treatment of acute PE patients selected by the Hestia clinical decision rule alone is safe Additional prognostic assessment based on NT-proBNP levels seemed not to affect the prognosis Yealy editorial: Yealy DM Am J Resp Crit Care Med 2016;194:

19 Future perspective: Efficiency study Home PE study: Hestia vs spesi score (NCT )

20 Vesta Study Investigators LUMC, Leiden: MV Huisman, FA Klok, PL den Exter, W Zondag Diakonessenhuis, Utrecht: E Cornage, MA van de Ree Groene Hart Hospital, Gouda: H Peltenburg, T Koster, F Besemer Medisch Spectrum Twente, Enschede: M Eijsvogel Rijnland Hospital, Leiderdorp: GJPM Jonkers, C Ootjers, K de Groot Medisch Centrum Haaglanden, Den Haag: MJM de Vreede, ICM Mos Rode Kruis Hospital, Beverwijk: LM Faber HAGA Hospital, Den Haag: M van Gerwen, A Mairuhu Bronovo Hospital, Den Haag: LT Vlasveld, T Langeveld Spaarne Hosptital, Hoofddorp: C Onstijn, CF Melissant VUMC, Amsterdam: HMA Hofstee, MHH Kramer Rijnstate Ziekenhuis, Arnhem: MMC Hovens Diaconessenhuis, Leiden: J Dolsma Reinier de Graaf Gasthuis, Delft: RE Brouwer Van Weel Bethesda Hospital, Dirksland: KW van Kralingen Ikazia Hospital, Rotterdam: R Heller Amphia Hospital, Breda: M Grootenboers

21 Enrollment Assessed for eligibility (n=1102)) Randomized (n=558) Excluded: (n=544) Hemodynamically unstable (n=33) Thrombolysis (n= 2) High bleeding risk (n=13) Oxygen supply (n= 182) Intravenous pain medication (n= 17) Already receiving anticoagulants (n=19) Documented HIT (n=2) Uncontrolled hypertension (n=9) Severe renal insufficiency (n=2) Pregnant (n=5) Medical or social reasons (n=129) Age < 18 years (n=2) Symptoms >14 days (n=63) Life expectancy < 3 months (n=10) Inaccessible for follow-up (n=7) Previous participation in this trial (n=4) Refusal of consent (n=15) Eligible but not randomized (n=30) Allocated to undergo NT-proBNP testing (n=279) Consent withdrawn < 24H (n=1) Diagnosis of PE refuted < 24H (n=3) Lost to follow-up (n=0) Allocation Follow-Up n=550 Allocated to direct discharge (n=279) Consent withdrawn < 24H (n=2) Diagnosis of PE refuted < 24H (n =2) Lost to follow-up (n=0)