Tissue plasminogen activator for the treatment of adults with critical COVID-19: A pilot randomized clinical trial

Rashidi, Farid; Rezaeifar, Parisa; Sadeghipour, Parham; Ghodrati, Samad; Bakhshandeh, Hooman; Mousavi-Aghdas, Seyed Ali; Sadeghi, Armin; Sharifi, Akbar; Valizadeh, Hassan; Mikaeili, Haleh; Rafiee, Farnaz; Navarbaf, Zahar; Farajian, Gita; Bikdeli, Behnood; Ansarin, Khalil

doi:10.1016/j.thromres.2021.12.003

Cited by 13 publications

(23 citation statements)

References 9 publications

(14 reference statements)

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“…Our systematic search resulted in 17,114 eligible studies (8749 from the search on 18 October 2021 and 8365 from 23 May 2022). After the selection process, 14 articles were included in the meta-analysis [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 50 , 51 , 52 , 53 , 54 , 55 , 56 ] and 15 [ 57 ] articles in the systematic review. Figure 1 shows the PRISMA 2020 Flow diagram of the updated search, and the one for the initial search can be found in Supplementary material (Figure S1) [ 58 ].…”

Section: Resultsmentioning

confidence: 99%

“…The included open-label studies were conducted between April 2020 and September 2021 in 15 countries [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 50 , 51 , 52 , 53 , 54 , 55 , 56 ]. In total, they enrolled 6253 adult patients with an average age above 50 years in the cohorts.…”

Section: Resultsmentioning

confidence: 99%

“…In total, they enrolled 6253 adult patients with an average age above 50 years in the cohorts. Seven studies included patients with severe disease [ 50 , 51 , 52 , 53 , 54 , 55 , 56 ], seven with moderate disease at presentation, and one with mild disease [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 57 ]. The eligibility criteria of trials included higher than the upper limit of normal D-dimer levels or DIC score ≥3 in ten of the included studies [ 19 , 21 , 22 , 24 , 25 , 50 , 51 , 52 , 53 , 54 , 56 ].…”

Section: Resultsmentioning

confidence: 99%

“…Seven studies included patients with severe disease [ 50 , 51 , 52 , 53 , 54 , 55 , 56 ], seven with moderate disease at presentation, and one with mild disease [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 57 ]. The eligibility criteria of trials included higher than the upper limit of normal D-dimer levels or DIC score ≥3 in ten of the included studies [ 19 , 21 , 22 , 24 , 25 , 50 , 51 , 52 , 53 , 54 , 56 ]. Four studies compared intermediate dose thromboprophylaxis to standard dose [ 23 , 52 , 55 ]; among them, one was a three-arm study that included therapeutic anticoagulation as well [ 25 ].…”

Section: Resultsmentioning

confidence: 99%

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Higher Dose Anticoagulation Cannot Prevent Disease Progression in COVID-19 Patients: A Systematic Review and Meta-Analysis

et al. 2022

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Implementation of higher dose (HD) thromboprophylaxis has been considered in patients infected with coronavirus disease 2019 (COVID-19). Our aim was to compare HD to standard dose (SD) thromboprophylaxis in COVID-19 patients. The protocol is registered on PROSPERO (CRD42021284808). We searched for randomised controlled studies (CENTRAL, Embase, Medline and medRxviv) that compared HD to SD anticoagulation in COVID-19 and analysed outcomes such as mortality, thrombotic events, bleedings, and disease progression. The statistical analyses were made using the random effects model. Fourteen articles were included (6253 patients). HD compared with SD showed no difference in mortality (OR 0.83 [95% CI 0.54–1.28]). The use of HD was associated with a decreased risk of thrombosis (OR 0.58 [95% CI 0.44–0.76]), although with an increased risk of major bleeding (OR 1.64 [95% CI 1.25–2.16]). The cohort with D-dimer < 1 mg/mL showed no effect (OR 1.19 [95% CI 0.67–2.11]), but in the case of D-dimer > 1 mg/mL, a tendency of lower risk in the HD group was observed (OR 0.56 [95% CI 0.31–1.00]). The need for intubation in moderately ill patients showed a nonsignificant lower likelihood in the HD group (OR 0.82 [95% CI 0.63–1.08]). We cannot advocate for HD in all COVID-19 patients, although it shows some nonsignificant benefits on disease progression in those with elevated D-dimer who do not need ICU admission.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Higher Dose Anticoagulation Cannot Prevent Disease Progression in COVID-19 Patients: A Systematic Review and Meta-Analysis

et al. 2022

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“…As limited as our experience may be, long-term echocardiographic data appeared reassuring. A recent pilot trial showed that low-dose systemic thrombolysis compared to anticoagulation alone did not seem to improve surrogate respiratory parameters among critically ill COVID-19 patients [ 27 ]. A number of interventional studies are ongoing to test whether different thrombolytic strategies may improve the survival and outcomes of COVID-19 patients with or without thromboembolic complications.…”

Section: Discussionmentioning

confidence: 99%

Fixed-Dose Ultrasound-Assisted Catheter-Directed Thrombolysis for Acute Pulmonary Embolism Associated with COVID-19

Voci

Zbinden

Micieli

et al. 2022

Viruses

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Background. Fixed-dose ultrasound-assisted catheter-directed thrombolysis (USAT) rapidly improves hemodynamic parameters and reverses right ventricular dysfunction caused by acute pulmonary embolism (PE). The effectiveness of USAT for acute PE associated with coronavirus disease 2019 (COVID-19) is unknown. Methods and results. The study population of this cohort study consisted of 36 patients with an intermediate-high- or high-risk acute PE treated with a fixed low-dose USAT protocol (r-tPA 10–20 mg/15 h). Of these, 9 patients tested positive for COVID-19 and were age–sex-matched to 27 patients without COVID-19. The USAT protocol included, beyond the infusion of recombinant tissue plasminogen activator, anti-Xa-activity-adjusted unfractionated heparin therapy (target 0.3–0.7 U/mL). The study outcomes were the invasively measured mean pulmonary arterial pressure (mPAP) before and at completion of USAT, and the National Early Warning Score (NEWS), according to which more points indicate more severe hemodynamic impairment. Twenty-four (66.7%) patients were men; the mean age was 67 ± 14 years. Mean ± standard deviation mPAP decreased from 32.3 ± 8.3 to 22.4 ± 7.0 mmHg among COVID-19 patients and from 35.4 ± 9.7 to 24.6 ± 7.0 mmHg among unexposed, with no difference in the relative improvement between groups (p = 0.84). Within 12 h of USAT start, the median NEWS decreased from six (Q1–Q3: 4–8) to three (Q1–Q3: 2–4) points among COVID-19 patients and from four (Q1–Q3: 2–6) to two (Q1–Q3: 2–3) points among unexposed (p = 0.29). One COVID-19 patient died due to COVID-19-related complications 14 days after acute PE. No major bleeding events occurred. Conclusions. Among patients with COVID-19-associated acute PE, mPAP rapidly decreased during USAT with a concomitant progressive improvement of the NEWS. The magnitude of mPAP reduction was similar in patients with and without COVID-19.

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Effect of therapeutic anticoagulation on gas exchange in mechanically ventilated COVID-19 patients: A secondary analysis of the COVID-HEP trial

Pantet

Combescure

Ltaief

et al. 2023

Thrombosis Research

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Tissue plasminogen activator for the treatment of adults with critical COVID-19: A pilot randomized clinical trial

Cited by 13 publications

References 9 publications

Higher Dose Anticoagulation Cannot Prevent Disease Progression in COVID-19 Patients: A Systematic Review and Meta-Analysis

Higher Dose Anticoagulation Cannot Prevent Disease Progression in COVID-19 Patients: A Systematic Review and Meta-Analysis

Fixed-Dose Ultrasound-Assisted Catheter-Directed Thrombolysis for Acute Pulmonary Embolism Associated with COVID-19

Effect of therapeutic anticoagulation on gas exchange in mechanically ventilated COVID-19 patients: A secondary analysis of the COVID-HEP trial

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