scholarly journals Efficacy and safety of a monodisperse solid-in-oil-in-water emulsion in transcatheter arterial chemoembolization in a rabbit VX2 tumor model

2019 ◽  
Author(s):  
Daisuke Yasui ◽  
Aya Yamane ◽  
Hiroshi Itoh ◽  
Masayuki Kobayashi ◽  
Shin-ichiro Kumita
Keyword(s):  
Adverse Events ◽  
Transcatheter Arterial Chemoembolization ◽  
Iodine Concentration ◽  
Control Group ◽  
Efficacy And Safety ◽  
Water Emulsion ◽  
Left Liver Lobe ◽  
Vx2 Tumor ◽  
Experimental Group ◽  
Arterial Chemoembolization

AbstractTranscatheter arterial chemoembolization (TACE) is a standard treatment for unresectable hepatocellular carcinoma; however, it does not always result in tumor control. Nevertheless, treatment outcome can be improved with monodisperse emulsions of anticancer agents. In this study, the efficacy and safety of a monodisperse miriplatin-Lipiodol emulsion were evaluated in Japanese white rabbits. VX2 tumor was implanted into the left liver lobe of each rabbit. The animals were divided into control and experimental groups (of five animals each) and respectively administered a conventional miriplatin suspension or the emulsion via the left hepatic artery. Computed tomography (CT) was performed before, immediately after, and two days following TACE. All rabbits were sacrificed two days after the procedure. Each tumor was removed and cut in half for assessment of iodine concentration in one half by mass spectroscopy and evaluation of Lipiodol accumulation and adverse events in the other half. Mean Hounsfield unit (HU) values were measured using plain CT images taken before and after TACE. Iodine concentration was higher in the experimental group [1100 (750–1500) ppm] than in the control group [840 (660–1800) ppm]. Additionally, the HU value for the experimental group was higher than that for the control group immediately after [199.6 (134.0– 301.7) vs. 165.3 (131.4–280.5)] and two days after [114.2 (56.1–229.8) vs. 58.3 (42.9–132.5)] TACE. Cholecystitis was observed in one rabbit in the control group. Ischemic bile duct injury was not observed in any group. The results show that Lipiodol accumulation and retention in VX2 tumor may be improved by using a monodisperse emulsion. Moreover, no significant adverse events are associated with the use of the emulsion.

scholarly journals Anerning Granule for Community Acquired Pneumonia: Protocol for Randomized, Double-Blind, Single-Dummy, Parallel Control of Placebo, Multicenter Clinical Trial

2021 ◽  
Author(s):  
Menghua Sun ◽  
Jian Lyu ◽  
Yi-li Zhang ◽  
Xu Wei ◽  
Li-dan Zhang ◽  
...  
Keyword(s):  
Adverse Events ◽  
Community Acquired Pneumonia ◽  
Clinical Treatment ◽  
Secondary Outcome ◽  
Control Group ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Ceftriaxone Sodium ◽  
Parallel Control ◽  
Experimental Group

Abstract Background: Community acquired pneumonia (CAP) in children is one of the common clinical diseases and infectious diseases threatening the health of the population. CAP has complicated causes, closely related to region, season, age, and primary disease. It is the most common cause of children being hospitalized and the first cause of death for children under 5 years old. At present, the clinical treatment is mainly antibiotics, but abuse and non-standard combination of antibiotics have led to increasing antibiotic resistance. Anerning Granules have the functions of clearing away heat and removing wind, reducing phlegm and relieving cough, and improving cough symptoms and lung signs. Thus, this study aims to evaluate the efficacy and safety of Anerning Granules (AEN) in the treatment of community-acquired pneumonia in children, and to explore whether AEN can reduce the use of antibiotics and have a good effect on the clinical treatment of CAP.Methods and analysis: this study, a randomized, double-blind, single-dummy, parallel control of placebo, multicenter clinical study will be established in 7 hospitals in the same period. A total of 216 patients with community-acquired pneumonia will be randomly allocated at a ratio of 2:1 to two groups: experimental group, control group. The experimental group receives Anerning Granules plus ceftriaxone sodium; the control group receives AEN placebo plus ceftriaxone sodium. Each group will be treated for ten days, and a stage effect evaluation will be conducted on the sixth day. The primary outcome is the end of antibiotics in frequency (DDDs) and effective rate. Secondary outcome measures of effectiveness are the full fever time, sore throat onset time, and safety assessment. Outcomes will be assessed at baseline and after treatment. In addition, adverse events will be monitored throughout the trial process and must be traced to be resolved.Discussion: This study protocol will provide the research data regarding the efficacy and safety of AEN for the treatment of community-acquired pneumonia in children. The first aim is to determine whether Anerning Granules can reduce the use of antibiotics; the second aim is to evaluate the effectiveness of Anerning Granules combined with ceftriaxone sodium in the treatment of children with community-acquired pneumonia. The third aim is to observe the safety of clinical application of Anerning Granules. The results of this study will improve the rational use of drugs, especially the rational application of antibiotics. It will also enable safety evaluation from laboratory indices of adverse events, which will provide reliable evidence for clinical treatment.Trial registration: Clinicaltrials.gov identifier: NCT03675178, registered on 16 September 2018.

Efficacy and safety of apatinib combined with TACE in patients with hepatocellular carcinoma refractory to transcatheter arterial chemoembolization.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15504-e15504
Author(s):  
Wei Zhang ◽  
Zhiping Yan
Keyword(s):  
Hepatocellular Carcinoma ◽  
Adverse Events ◽  
Transcatheter Arterial Chemoembolization ◽  
Advanced Hepatocellular Carcinoma ◽  
Efficacy And Safety ◽  
Phase 2 Study ◽  
Grade 3 ◽  
Treatment Safety ◽  
Unacceptable Toxicity ◽  
Arterial Chemoembolization

e15504 Background: Effective options for patients with advanced hepatocellular carcinoma (HCC) are urgently needed. Studies have shown that combination of sorafenib with TACE could imorove survival for the treatment of locoregional HCCs. Apatinib is a novel and highly selective inhibitor of VEGFR2 tyrosine kinase. We were aiming to explore the efficacy and safety of apatinib combined with TACE in patients with hepatocellular carcinoma refractory to transcatheter arterial chemoembolization. Methods: This was a single-center single-arm phase 2 study. The key inclusion criteria included: (1) Histologicaly and cytologicaly diagnosed as Hepatocellular carcinoma of the liver ( HCC ) and with at least one imaging examination of measurable lesions, CT or MR scan long diameter of tumor ≥ 10 mm. (2) BCLC B / C; (3) Progressed after at least twice TACE. Eligible pts received apatinib at 500 mg/day for a maximum after TACE 4-7 days, and TACE treatment was performed after 4 days of discontinuation of apatinib until unacceptable toxicity or tumor recurrence. The primary endpoint was time to progression (TTP), which was defined as the time from enrollment to disease progression. The secondary endpoint was overall survival (OS) and treatment safety. Results: From May 27, 2018 to Oct 12, 2019, 22 pts wereenrolled. 5 pts received TACE more than 5 times, and 17 pts received TACE within 4 times. For 20 evaluable pts, two pts achieved partial response (10%), and 13 patients achieved stable disease. The ORR and DCR were 10% and 75%, respectively. At the cutoff data of Nov 4, 2019, 5 pts were still on treatment. 16 recurrenced and 5 death occurred. The mTTP was 5.09 months (95% CI, 3.48-7.16), and the mOS was not reached. Treatment-related adverse events occurred in 12 pts (60%). Seven grade 3 or 4 adverse events were reported (35%), respectively wereascites (2), platelet count decrease (1), elevated ALT/AST (1), hypertension (1), proteinuria (1) and nausea (1). None of the treatment related AEs was fatal. Conclusions: Apatinib combined with TACE might be effective and tolerant in patients with hepatocellular carcinoma refractory to transcatheter arterial chemoembolization. Clinical trial information: NCT03510416.

Characteristics of COVID-19 and possibilities of early causal therapy. Results of favipiravir use in clinical practice

2020 ◽  
Vol 18 (3) ◽  
pp. 30-40
Author(s):  
L.A. Balykova ◽  
◽  
A.V. Govorov ◽  
A.O. Vasilyev ◽  
E.N. Simakina ◽  
...  
Keyword(s):  
Adverse Events ◽  
Clinical Improvement ◽  
Standard Therapy ◽  
Control Group ◽  
Efficacy And Safety ◽  
Virus Elimination ◽  
Good Safety Profile ◽  
Causal Therapy ◽  
Lung Condition ◽  
Experimental Group

This paper provides the results of a study evaluating the efficacy and safety of etiotropic therapy in patients hospitalized with SARS-CoV-2 infection. Objective. Тo evaluate the efficacy and safety of favipiravir (Areplivir) in patients with coronavirus disease 2019 (COVID-19) and compare it with recommended standard therapy. Patients and methods. Two hundred men and women aged between 18 and 80 years with COVID-19 were randomized into this study. The experimental group included patients who received favipiravir, whereas the control group comprised patients who received causal therapy in accordance with the latest version of the temporary methodical recommendations of the Ministry of Health of Russia ‘Prevention, diagnosis, and treatment of coronavirus infection (COVID-19).’ The efficacy and safety of therapy were evaluated by assessing clinical improvement using the WHO Ordinal Scale for Clinical Improvement, clinical and laboratory parameters, findings of chest computed tomography (CT), and elimination of SARS-CoV-2. We also analyzed the frequency and type of adverse events, need for invasive and non-invasive ventilation, and death rates. Results. Our analysis has demonstrated significant benefits of favipiravir over standard therapy in terms of the time to clinical improvement (in the experimental group it was 4 days shorter on average), time to recovery, frequency of recovery after 10 days (44% of patients from the experimental group and 10% of patients from the control group had no clinical signs of the disease at this time-point), and frequency of virus elimination by day 10 of therapy. Treatment with favipiravir was associated with a significant improvement in the lung condition (according to CT), normalization of laboratory parameters, and saturation level. Favipiravir has demonstrated a good safety profile similar to that of standard therapy. There was no difference in the frequency of adverse events between the experimental and control groups. Conclusion. The use of favipiravir for the treatment of SARS-CoV-2 infection reduced the time to clinical improvement by 4 days on average compared to standard therapy, ensured improvement of the lung condition (according to CT scans), and facilitated virus elimination in more than 90% of patients, thereby promoting faster recovery. Favipiravir had a good safety profile and was well tolerated by patients. This treatment regimen was shown to be effective, sufficient, and clinically reasonable to achieve good outcomes. Timely initiation of therapy with favipiravir (Areplivir) improves disease prognosis and reduces the global socioeconomic burden of the current pandemic. Key words: COVID-19, Areplivir, coronavirus, causal therapy, favipiravir

scholarly journals Application of Traditional Chinese Medicine Combined with TACE in Patients with Primary Hepatocellular Carcinoma and Its Effect on Liver Function

1970 ◽  
Vol 1 (2) ◽  
Author(s):  
Haibin Ding
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Liver Cancer ◽  
Liver Function ◽  
Recurrence Rate ◽  
Transcatheter Arterial Chemoembolization ◽  
Primary Liver Cancer ◽  
Control Group ◽  
Experimental Group ◽  
Arterial Chemoembolization

Objective: To analyze the effects of Chinese herbal medicine combined with transcatheter arterial chemoembolization (TACE) on liver function in patients with primary hepatocellularCarcinoma (HCC). Methods: 122 patients with primary hepatocellular carcinoma admitted in our hospital from March 2014 to October 2016 were divided into experimental group and control group according to the digital table. The number of each group was the same. The patients in the control group were treated by transcatheter arterial chemoembolization. The experimental group was treated with traditional Chinese medicine on the basis of the control group. SPSS20.0 statistical software for statistical analysis of two groups of patients with short-term effect, follow-up of one year primary liver cancer recurrence rate, before and after treatment WBC count, liver function (alanine aminotransferase), alpha-fetoprotein and Karnofsky index parameters. Results: ①The total effective rate of the experimental group was significantly higher than that of the control group (P <0.05); ②The relapse rate of theexperimental group was significantly lower than that of the control group (P <0.05); ③ Before the treatment, the patients in the two groups had significantly higher recurrence rate than those in the control group (P <0.05). After treatment, the white blood cell count, liver function and alpha-fetoprotein levels in the experimental group were significantly better than those in thecontrol group (P <0.05), but no significant difference was found between the two groups (P<0.05). ④ The Karnofsky score of the experimental group was significantly higher than that of the control group (P<0.05). Conclusion: Chinese medicine combined with transcatheter arterial chemoembolization in patients with primary liver cancer in the application value is relatively high.

scholarly journals Effects of Acupressure on Fatigue and Depression in Hepatocellular Carcinoma Patients Treated with Transcatheter Arterial Chemoembolization: A Quasi-Experimental Study

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Su-Chen Lan ◽  
Yueh-E Lin ◽  
Shu-Ching Chen ◽  
Yu-Fang Lin ◽  
Yu-Jen Wang
Keyword(s):  
Transcatheter Arterial Chemoembolization ◽  
Discharge Planning ◽  
Depression Scale ◽  
Control Group ◽  
Control Groups ◽  
Quasi Experimental ◽  
And Control ◽  
Experimental Group ◽  
Improve Fatigue ◽  
Arterial Chemoembolization

This study was to examine the effects of acupressure on fatigue and depression in HCC patients undergoing TACE. A quasiexperimental study design was used. Patients were evaluated at five time points: before treatment (T1) and 2, 3, 4, and 5 days after treating TACE (T2, T3, T4, and T5). Fatigue and depression were assessed by a VAS fatigue scale and a VAS depression scale at each time point. TFRS and BDI were administered at T1 and T5. Patients’ fatigue and depression were significantly higher at T5 than at T1 in two groups. Fatigue and depression increased in both the experimental and control groups’ patients over the five days of hospitalization during which TACE and chemotherapy were administered. The experimental group had significantly less fatigue than the control group, with lower subscale scores on physical, psychosocial, daily, and overall fatigue. There were no differences between the groups on depression. At posttest, the experimental group experienced lower physical, psychosocial, daily, and overall fatigue than the control group. Acupressure can improve fatigue in HCC patients during treatment with TACE but did not alleviate depression. Discharge planning should include home care for management of fatigue and depression.

scholarly journals Efficacy and Safety of Radiotherapy Plus Anti-PD1 Versus Transcatheter Arterial Chemoembolization Plus Sorafenib For Advanced Hepatocellular Carcinoma: a Real-World Study

2021 ◽  
Author(s):  
Jian-Xu Li ◽  
Wen-Xiang Deng ◽  
Shi-Ting Huang ◽  
Xiao-Feng Lin ◽  
Mei-Ying Long ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Adverse Events ◽  
Real World ◽  
Transcatheter Arterial Chemoembolization ◽  
Objective Response ◽  
Advanced Hepatocellular Carcinoma ◽  
Efficacy And Safety ◽  
Advanced Hcc ◽  
Sorafenib Group ◽  
Arterial Chemoembolization

Abstract Background: The combination of transcatheter arterial chemoembolization (TACE) plus sorafenib prolonged progression-free survival (PFS) and overall survival (OS) than sorafenib or TACE monotherapy for patients with hepatocellular carcinoma (HCC). This study assessed the efficacy and safety of radiotherapy (RT) plus monoclonal antibody against programmed cell death 1 (anti-PD1) versus TACE plus sorafenib for patients with advanced HCC.Methods: Patients with advanced HCC who treated with RT plus anti-PD1 and TACE plus sorafenib were enrolled. Objective response rate (ORR), PFS, disease control rate (DCR) and OS were calculated to assess the antitumor response and the treatment-related adverse events to the safety.Results: Between January 2018 to March 2021, 37 patients underwent RT plus anti-PD1 and 41 patients underwent TACE plus sorafenib. The baseline characteristics between the two groups were comparable. The ORR and DCR were significantly higher in the RT+PD1 group than the TACE plus sorafenib group according to RECIST 1.1 (54.05% vs 12.20%, P < 0.001; 70.27% vs 46.37%, P = 0.041; respectively) and according to mRECIST (56.76% vs 31.71%, P = 0.039; 70.27% vs 46.37%, P = 0.041; respectively). RT plus anti-PD1 provided significantly better PFS (HR, 0.51; 95% CI 0.30-0.86; p=0.017) than TACE plus sorafenib. Moreover, patients with RT plus anti-PD1 had significantly higher 3-, 6-, and 9-month OS rates than those with TACE plus sorafenib(97.3% vs 92.30%, P < 0.001; 91.89% vs 68.60%, P < 0.001; 75.5% vs 60.60%, P < 0.001; respectively). The median OS was more favorable 17.4 months for the RT+PD1 group and 11.9 months for the TACE plus sorafenib group. No treatment-related death was observed. Grade 3 or more treatment-related adverse events (TRAEs) occurred significantly less in patients in the RT+PD1 group than the TACE plus sorafenib group (29.7% vs 75.6%, p < 0.001), and all TRAEs were manageable.Conclusions: In this real-world study, RT plus anti-PD1 showed significantly promising efficacy and manageable safety than TACE plus sorafenib in patients with advanced HCC. Toxicities were manageable, with no unexpected safety signals. The study provides evidence on a new therapeutic method in the treatment of advanced HCC.

scholarly journals Efficacy and Safety of the Arsenic Trioxide/Lipiodol Emulsion in the Transcatheter Arterial Chemoembolization Combined with Apatinib in the Treatment of Advanced Hepatocellular Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Zhaonan Li ◽  
Quanjing Chen ◽  
Wenguang Zhang ◽  
Guangyan Si ◽  
Jing Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Adverse Events ◽  
Transcatheter Arterial Chemoembolization ◽  
Tumor Burden ◽  
Advanced Hepatocellular Carcinoma ◽  
Efficacy And Safety ◽  
Advanced Hcc ◽  
Grade 3 ◽  
Lipiodol Emulsion ◽  
Arterial Chemoembolization

Purpose. The goal of this study was to assess the clinical efficacy and safety of the arsenic trioxide (ATO)/lipiodol emulsion in the transcatheter arterial chemoembolization (TACE) combined with apatinib in the treatment of advanced hepatocellular carcinoma (HCC). Methods. From December 2015 to February 2017, a total of 87 patients were consecutively enrolled and underwent ATO-TACE (aTACE) combined with apatinib in the treatment of advanced HCC. The treatment response and adverse events were assessed at the first month and third month after aTACE therapy. Progression-free survival (PFS), overall survival (OS), and treatment-related adverse events were also analyzed. Results. 87 patients (57 men; 30 women) were enrolled in the present study. Compared to that at the pre-aTACE examination, the levels of AST and ALT were elevated at the first week after procedure (65.84 U/L ± 22.93 U/L vs. 54.15 U/L ± 19.60 U/L, p = 0.032 ; 63.44 U/L ± 22.50 U/L vs. 51.60 U/L ± 13.89 U/L, p = 0.027 , respectively). Most of the adverse events were grade 1 or 2 according to National Cancer Institute Common Terminology Criteria for Adverse Event (CTCAE). Of the exception, 4 persons (2%) did have grade 3 hand-foot skin reactions, 1 (1%) had grade 3 diarrhea, 1 (1%) had grade 3 hypertension, and 3 (3%) had grade 3 proteinuria and forced to reduce the dose of apatinib by half. The survival analysis of the combination with aTACE and apatinib therapy found that the median PFS was 10.2 months (95% CI: 8.543–11.857), and the median OS was 23.300 months (95% CI: 20.833–25.767). Additionally, both univariate and multivariate Cox regression revealed that the tumor burden (≤50%) and the patients without portal vein tumor thrombus (PVTT) significantly impacted the patient’s PFS and OS and were related to better survival. Conclusion. aTACE combined with apatinib is a safe and promising treatment approach for patients with advanced HCC. Additionally, tumor burden (≤50%) and the patients without PVTT are associated with better PFS and OS.

scholarly journals Effects of Shorten Bed Rest Time on Back Pain and Vascular Complication in Patients with Hepatocellular Carcinoma Receiving Transcatheter Arterial Chemoembolization

2017 ◽  
Vol 35 (3) ◽  
pp. 239
Author(s):  
Suthisa Temtap ◽  
Rungtip Udomvisatson ◽  
Kittikorn Nilmanat
Keyword(s):  
Hepatocellular Carcinoma ◽  
Back Pain ◽  
Transcatheter Arterial Chemoembolization ◽  
Vascular Complications ◽  
Bed Rest ◽  
Vascular Complication ◽  
Control Group ◽  
Rest Time ◽  
Experimental Group ◽  
Arterial Chemoembolization

Objective: To test the effect of bed rest time reduction on back pain and vascular complication in patients with hepatocellular carcinoma after transcatheter arterial chemoembolization (TACE).Material and Method: This study was two-group randomized controlled trial. A total of 54 patients with hepatocellular carcinoma, receiving TACE enrolled from October 2015-November 2016, were purposively selected and randomly assigned equally to receive either 6 hours (the control group) or 3 hours (the experimental group) of bed rest after TACE was achieved. Patients in both groups were evaluated back pain by the pain Numerical Rating Scale and vascular complications by Hematoma Formation and Bleeding Scale. Data were analyzed by chi-square test and Mann-Whitney U-test.Results: The mean total score on back pain in the experimental group was significantly lower than that of the control group at 6 and 8 hours following TACE (p-value< 0.000). No vascular complications was found in both the groups.Conclusion: Reducing bed rest time from 6 hours to 3 hours of patients following TACE can decrease the severity of back pain and has no effect on the incidence of vascular complications.

scholarly journals Improved Efficacy of Transcatheter Arterial Chemoembolization Using Warmed Miriplatin for Hepatocellular Carcinoma

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Daisuke Yasui ◽  
Satoru Murata ◽  
Shiro Onozawa ◽  
Takahiko Mine ◽  
Tatsuo Ueda ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Adverse Events ◽  
Odds Ratio ◽  
Transcatheter Arterial Chemoembolization ◽  
Response Rate ◽  
Objective Response ◽  
Alanine Transaminase ◽  
Efficacy And Safety ◽  
The Common ◽  
Arterial Chemoembolization

The aim of this study was to evaluate the efficacy and safety of transcatheter arterial chemoembolization (TACE) using warmed and nonwarmed miriplatin for hepatocellular carcinoma. Eighty patients (117 nodules), treated between January 2010 and June 2013, were evaluated. Thirty-two and 85 nodules were treated with nonwarmed and warmed miriplatin, respectively. The efficacy of TACE was evaluated on a per nodule basis according to treatment effect (TE). Adverse events were evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. TE grades were significantly improved in the warmed group compared to the nonwarmed group (nonwarmed: TE 4, 12.5%; TE 3, 0%; TE 2, 15.6%; TE 1, 71.9%; warmed: TE 4, 34.1%; TE 3, 5.9%; TE 2, 9.4%; TE 1, 50.6%;P=0.017) . Multivariate analysis revealed significant impact of warming miriplatin on objective response rate (odds ratio, 12.35; 95% confidence interval, 2.90–90.0;P=0.0028). CTCAE grades of elevated aspartate and alanine transaminase after TACE were significantly higher in the warmed group (P=0.0083and 0.0068, resp.); however, all adverse events were only transient. The use of warmed miriplatin in TACE significantly improved TE without causing serious complications.

scholarly journals Methylprednisolone Pulses Plus Tacrolimus in Addition to Standard of Care vs. Standard of Care Alone in Patients With Severe COVID-19. A Randomized Controlled Trial

2021 ◽  
Vol 8 ◽  
Author(s):  
Xavier Solanich ◽  
Arnau Antolí ◽  
Gemma Rocamora-Blanch ◽  
Núria Padullés ◽  
Marta Fanlo-Maresma ◽  
...  
Keyword(s):  
Adverse Events ◽  
Experimental Treatment ◽  
Standard Of Care ◽  
Experimental Therapy ◽  
Control Group ◽  
Efficacy And Safety ◽  
All Cause Mortality ◽  
Secondary Outcomes ◽  
Experimental Group ◽  
Clinical Stability

Introduction: Severe lung injury is triggered by both the SARS-CoV-2 infection and the subsequent host-immune response in some COVID-19 patients.Methods: We conducted a randomized, single-center, open-label, phase II trial with the aim to evaluate the efficacy and safety of methylprednisolone pulses and tacrolimus plus standard of care (SoC) vs. SoC alone, in hospitalized patients with severe COVID-19. The primary outcome was time to clinical stability within 56 days after randomization.Results: From April 1 to May 2, 2020, 55 patients were prospectively included for subsequent randomization; 27 were assigned to the experimental group and 28 to the control group. The experimental treatment was not associated with a difference in time to clinical stability (hazard ratio 0.73 [95% CI 0.39–1.37]) nor most secondary outcomes. Median methylprednisolone cumulative doses were significantly lower (360 mg [IQR 360–842] vs. 870 mg [IQR 364–1451]; p = 0.007), and administered for a shorter time (median of 4.00 days [3.00–17.5] vs. 18.5 days [3.00–53.2]; p = 0.011) in the experimental group than in the control group. Although not statistically significant, those receiving the experimental therapy showed a numerically lower all-cause mortality than those receiving SoC, especially at day 10 [2 (7.41%) vs. 5 (17.9%); OR 0.39 (95% CI 0.05–2.1); p = 0.282]. The total number of non-serious adverse events was 42 in each the two groups. Those receiving experimental treatment had a numerically higher rate of non-serious infectious adverse events [16 (38%) vs. 10 (24%)] and serious infectious adverse events [7 (35%) vs. 3 (23%)] than those receiving SoC.Conclusions: The combined use of methylprednisolone pulses plus tacrolimus, in addition to the SoC, did not significantly improve the time to clinical stability or other secondary outcomes compared with the SoC alone in severe COVID-19. Although not statistically significant, patients receiving the experimental therapy had numerically lower all-cause mortality than those receiving SoC, supporting recent non-randomized studies with calcineurin inhibitors. It is noteworthy that the present trial had a limited sample size and several other limitations. Therefore, further RCTs should be done to assess the efficacy and safety of tacrolimus to tackle the inflammatory stages of COVID-19.Clinical Trial Registration: Identifier [NCT04341038/EudraCT: 2020-001445-39].

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