Dataset Information

Pulmonary vasodilation by sildenafil in acute intermediate-high risk pulmonary embolism: a randomized explorative trial.

ABSTRACT:

Background

To investigate if acute pulmonary vasodilation by sildenafil improves right ventricular function in patients with acute intermediate-high risk pulmonary embolism (PE).

Methods

Single center, explorative trial. Patients with PE were randomized to a single oral dose of sildenafil 50 mg (n?=?10) or placebo (n?=?10) as add-on to conventional therapy. The time from hospital admission to study inclusion was 2.3?±?0.7 days. Right ventricular function was evaluated immediately before and shortly after (0.5-1.5 h) randomization by right heart catheterization (RHC), trans-thoracic echocardiography (TTE), and cardiac magnetic resonance (CMR). The primary efficacy endpoint was cardiac index measured by CMR.

Results

Patients had acute intermediate-high risk PE verified by computed tomography pulmonary angiography, systolic blood pressure of 135?±?18 (mean?±?SD) mmHg, increased right ventricular/left ventricular ratio 1.1?±?0.09 and increased troponin T 167?±?144 ng/L. Sildenafil treatment did not improve cardiac index compared to baseline (0.02?±?0.36 l/min/m2, p?=?0.89) and neither did placebo (0.00?±?0.34 l/min/m2, p?=?0.97). Sildenafil lowered mean arterial blood pressure (-?19?±?10 mmHg, p?ConclusionA single oral dose of sildenafil 50 mg did not improve cardiac index but lowered systemic blood pressure in patients with acute intermediate-high risk PE. The time from PE to intervention, a small patient sample size and low pulmonary vascular resistance are limitations of this study that should be considered when interpreting the results.

Trial registration

The trial was retrospectively registered at www.clinicaltrials.gov (NCT04283240) February 2nd 2020, https://clinicaltrials.gov/ct2/show/NCT04283240?term=NCT04283240&draw=2&rank=1 .

SUBMITTER: Andersen A

PROVIDER: S-EPMC7916297 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

Pulmonary vasodilation by sildenafil in acute intermediate-high risk pulmonary embolism: a randomized explorative trial.

Andersen Asger A Waziri Farhad F Schultz Jacob Gammelgaard JG Holmboe Sarah S Becker Søren Warberg SW Jensen Tage T Søndergaard Hanne Maare HM Dodt Karen Kaae KK May Ole O Mortensen Ulrik Markus UM Kim Won Yong WY Mellemkjær Søren S Nielsen-Kudsk Jens Erik JE

BMC pulmonary medicine 20210228 1

<h4>Background</h4>To investigate if acute pulmonary vasodilation by sildenafil improves right ventricular function in patients with acute intermediate-high risk pulmonary embolism (PE).<h4>Methods</h4>Single center, explorative trial. Patients with PE were randomized to a single oral dose of sildenafil 50 mg (n = 10) or placebo (n = 10) as add-on to conventional therapy. The time from hospital admission to study inclusion was 2.3 ± 0.7 days. Right ventricular function was evaluated immediately ...[more]

PMID: 33639897

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Project description:ImportanceThe optimal treatment of intermediate-high-risk pulmonary embolism (PE) remains unknown.ObjectiveTo assess the effect of conventional catheter-directed thrombolysis (cCDT) plus anticoagulation vs anticoagulation monotherapy in improving echocardiographic measures of right ventricle (RV) to left ventricle (LV) ratio in acute intermediate-high-risk PE.Design, setting, and participantsThe Catheter-Directed Thrombolysis vs Anticoagulation in Patients with Acute Intermediate-High-Risk Pulmonary Embolism (CANARY) trial was an open-label, randomized clinical trial of patients with intermediate-high-risk PE, conducted in 2 large cardiovascular centers in Tehran, Iran, between December 22, 2018, through February 2, 2020.InterventionsPatients were randomly assigned to cCDT (alteplase, 0.5 mg/catheter/h for 24 hours) plus heparin vs anticoagulation monotherapy.Main outcomes and measuresThe proportion of patients with a 3-month echocardiographic RV/LV ratio greater than 0.9, assessed by a core laboratory, was the primary outcome. The proportion of patients with an RV/LV ratio greater than 0.9 at 72 hours after randomization and the 3-month all-cause mortality were among secondary outcomes. Major bleeding (Bleeding Academic Research Consortium type 3 or 5) was the main safety outcome. A clinical events committee, masked to the treatment assignment, adjudicated clinical outcomes.ResultsThe study was prematurely stopped due to the COVID-19 pandemic after recruiting 94 patients (mean [SD] age, 58.4 [2.5] years; 27 women [29%]), of whom 85 patients completed the 3-month echocardiographic follow-up. Overall, 2 of 46 patients (4.3%) in the cCDT group and 5 of 39 patients (12.8%) in the anticoagulation monotherapy group met the primary outcome (odds ratio [OR], 0.31; 95% CI, 0.06-1.69; P = .24). The median (IQR) 3-month RV/LV ratio was significantly lower with cCDT (0.7 [0.6-0.7]) than with anticoagulation (0.8 [0.7-0.9); P = .01). An RV/LV ratio greater than 0.9 at 72 hours after randomization was observed in fewer patients treated with cCDT (13 of 48 [27.0%]) than anticoagulation (24 of 46 [52.1%]; OR, 0.34; 95% CI, 0.14-0.80; P = .01). Fewer patients assigned to cCDT experienced a 3-month composite of death or RV/LV greater than 0.9 (2 of 48 [4.3%] vs 8 of 46 [17.3%]; OR, 0.20; 95% CI, 0.04-1.03; P = .048). One case of nonfatal major gastrointestinal bleeding occurred in the cCDT group.Conclusions and relevanceThis prematurely terminated randomized clinical trial of patients with intermediate-high-risk PE was hypothesis-generating for improvement in some efficacy outcomes and acceptable rate of major bleeding for cCDT compared with anticoagulation monotherapy and provided support for a definitive clinical outcomes trial.Trial registrationClinicalTrials.gov Identifier: NCT05172115.

Dataset Information

Pulmonary vasodilation by sildenafil in acute intermediate-high risk pulmonary embolism: a randomized explorative trial.

Background

Methods

Results

Trial registration

Publications

Pulmonary vasodilation by sildenafil in acute intermediate-high risk pulmonary embolism: a randomized explorative trial.

Similar Datasets

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