A novel MSC-based immune induction strategy for ABO-incompatible liver transplantation: a phase I/II randomized, open-label, controlled trial

Abstract Background ABO-incompatible liver transplantation (ABO-i LT) has become a rescue therapeutic option for patients with severe hepatic failure. Although the use of rituximab greatly reduces the morbidity of antibody-mediated rejection (AMR), severe adverse effects, such as infection and biliary complications, still seriously threaten the survival of transplant recipients. The aim of this study was to evaluate the safety and feasibility of using mesenchymal stem cells (MSCs) to replace rituximab in ABO-i LT. Methods Twenty-two patients with severe hepatic failure undergoing ABO-i LT were enrolled and randomly divided into two groups: the MSC group and the rituximab group. The safety of the application of MSCs and the incidence of allograft rejection, including antibody-mediated rejection (AMR) and acute cellular rejection (ACR), were evaluated in both groups at the 2-year follow-up period as primary endpoints. Recipients and graft survival and other postoperative complications were compared as secondary endpoints. Results No severe MSC-related adverse events were observed during the trial. MSC treatment yielded comparable, if not better, results than rituximab at decreasing the incidence of acute rejection (9.1% vs 27.3%). Inspiringly, compared to those in the rituximab group, the rates of biliary complications (0% vs 45.5%) and infection (9.1% vs 81.8%) were significantly decreased in the MSC group. In addition, there were no significant differences in 2-year graft and recipient survival between the two groups (81.8% vs 72.7%). Conclusions Our data show that MSC transfusion is comparable to rituximab treatment for AMR prophylaxis following ABO-i LT. Additionally, the results indicate that MSCs are more beneficial to the prevention of infection and biliary complications and may be introduced as a novel immunosuppressive approach for ABO-i LT. Trial registration Trial registration: chictr.org.cn, ChiCTR2000037732. Registered 31 August 2020- Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=57074.

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A Novel MSC-Based Immune Induction Strategy in ABO-Incompatible Liver Transplantation: A Phase I/II Randomized, Open-Labeled, Controlled Trial

10.21203/rs.3.rs-111230/v1 ◽

2020 ◽

Author(s):

Yingcai Zhang ◽

Jiebin Zhang ◽

Huimin Yi ◽

Jun Zheng ◽

Jianye Cai ◽

...

Keyword(s):

Liver Transplantation ◽

Adverse Effects ◽

Hepatic Failure ◽

Therapeutic Option ◽

Controlled Trial ◽

Trial Registration ◽

Biliary Complications ◽

Antibody Mediated Rejection ◽

Induction Strategy ◽

Significant Difference

Abstract Background: ABO-incompatible liver transplantation (ABO-i LT) has become a rescue therapeutic option for severe hepatic failure patients. Although the use of rituximab greatly reduces the morbidity of antibody-mediated rejection (AMR), severe adverse effects, such as infection and biliary complications still seriously threatening the survival of the transplant recipients. The aim of this study is to evaluate the safety and feasibility of using mesenchymal stem cells (MSCs) to replace rituximab in ABO-i LT. Methods: 22 severe hepatic failure patients undergoing ABO-i LT were enrolled and randomly divided into two groups, including the MSC group and Rituximab group. The safety of the application of MSCs and the incidence of allograft rejection, including antibody-mediated rejection (AMR) and acute cellular rejection (ACR) were evaluated in both groups at 2-year follow-up period as primary endpoints. Recipients and graft survivals and other postoperative complications were compared as secondary endpoints. Results: No severe adverse effects occurred in the MSC group related to the MSC infusion. MSCs treatment obtained comparable, if not better, results to rituximab for decreasing the incidence of acute rejection, especially AMR (9.1% vs 27.3%). Inspiringly, compared to the Rituximab group, biliary complications (0% vs 45.5%) and infection (9.1% vs 81.8%), were significantly decreased in MSCs group. In addition, there were no significant difference in 2-year graft and recipient survivals in the two groups (81.8% vs 72.7%). Conclusions: Our data shows that MSCs transfusion is comparable to rituximab treatment for AMR prophylaxis following ABO-i LT. Additionally, the results indicate that MSC is more beneficial to the prevention of infection and biliary complications, which may be introduced as a novel immunosuppressive approach for ABO-i LT. Trial registration: Trial registration: chictr.org.cn, ChiCTR2000037732. Registered 31 August 2020- Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=57074.

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Otitis media outcomes of a combined 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine and 13-valent pneumococcal conjugate vaccine schedule at 1-2-4-6 months: PREVIX_COMBO, a 3-arm randomised controlled trial

BMC Pediatrics ◽

10.1186/s12887-021-02552-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Amanda Jane Leach ◽

Edward Kim Mulholland ◽

Mathuram Santosham ◽

Paul John Torzillo ◽

Peter McIntyre ◽

...

Keyword(s):

Haemophilus Influenzae ◽

Otitis Media ◽

Conjugate Vaccine ◽

Otitis Media With Effusion ◽

Controlled Trial ◽

Acute Otitis Media ◽

Trial Registration ◽

Open Label ◽

Suppurative Otitis Media ◽

Link Type

Abstract Background Aboriginal children living in Australian remote communities are at high risk of early and persistent otitis media, hearing loss, and social disadvantage. Streptococcus pneumoniae and non-typeable Haemophilus influenzae (NTHi) are the primary pathogens. We compared otitis media outcomes in infants randomised to either a combination of Synflorix™ (PHiD-CV10, with protein D of NTHi) and Prevenar13™ (PCV13, with 3, 6A, and 19A), with recommended schedules for each vaccine alone. We previously reported superior broader overall immunogenicity of the combination schedule at 7 months, and early superiority of PHiD-CV10 compared to PCV13 at 4 months. Methods In an open-label superiority trial, we randomised (1:1:1) Aboriginal infants at 28 to 38 days of age, to either Prevenar13™ (P) at 2–4-6 months (_PPP), Synflorix™ (S) at 2–4-6 months (_SSS), or Synflorix™ at 1–2-4 months plus Prevenar13™ at 6 months (SSSP). Ears were assessed using tympanometry at 1 and 2 months, combined with otoscopy at 4, 6, and 7 months. A worst ear diagnosis was made for each child visit according to a severity hierarchy of normal, otitis media with effusion (OME), acute otitis media without perforation (AOMwoP), AOM with perforation (AOMwiP), and chronic suppurative otitis media (CSOM). Results Between September 2011 and September 2017, 425 infants were allocated to _PPP(143), _SSS(141) or SSSP(141). Ear assessments were successful in 96% scheduled visits. At 7 months prevalence of any OM was 91, 86, and 90% in the _PPP, _SSS, and SSSP groups, respectively. There were no significant differences in prevalence of any form of otitis media between vaccine groups at any age. Combined group prevalence of any OM was 43, 57, 82, 87, and 89% at 1, 2, 4, 6, and 7 months of age, respectively. Of 388 infants with ear assessments at 4, 6 and 7 months, 277 (71.4%) had OM that met criteria for specialist referral; rAOM, pOME, or CSOM. Conclusions Despite superior broader overall immunogenicity of the combination schedule at 7 months, and early superiority of PHiD-CV10 compared to PCV13 at 4 months, there were no significant differences in prevalence of otitis media nor healthy ears throughout the first months of life. Trial registration ACTRN12610000544077 registered 06/07/2010 and ClinicalTrials.govNCT01174849 registered 04/08/2010.

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Evaluation of Convalescent Plasma versus Standard of Care for the Treatment of COVID-19 in Hospitalazed Patients: study protocol for a phase 2 randomized, open-label, controlled, multicenter trial

10.1101/2020.07.31.20165720 ◽

2020 ◽

Author(s):

Elena Diago-Sempere ◽

Jose Luis Bueno ◽

Aranzazu Sancho-Lopez ◽

Elena Munez-Rubio ◽

Ferran Torres ◽

...

Keyword(s):

Clinical Trial ◽

Respiratory Infections ◽

Controlled Trial ◽

Viral Disease ◽

Adult Patients ◽

Trial Registration ◽

Ordinal Scale ◽

Efficacy And Safety ◽

Open Label ◽

Link Type

Background: COVID-19 is a respiratory disease caused by a novel coronavirus (SARS-CoV-2) and causes substantial morbidity and mortality. At the time this clinical trial was planned, there were no available vaccine or therapeutic agents with proven efficacy, but the severity of the condition prompted the use of several pharmacological and non-pharmacological interventions. It has long been hypothesized that the use of convalescent plasma (CP) from infected patients who have developed an effective immune response is likely to be an option for the treatment of patients with a variety of severe acute respiratory infections (SARI) of viral etiology. The aim of this study is to assess the efficacy and safety of convalescent plasma in adult patients with severe COVID-19 pneumonia. Methods/Design: The ConPlas-19 study is a multicenter, randomized, open-label controlled trial. The protocol has been prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. The study has been planned to include 278 adult patients hospitalized with severe COVID-19 infection not requiring mechanical ventilation (invasive or non-invasive). Subjects are randomly assigned in a 1:1 ratio (139 per treatment arm), stratified by center, to receive intravenously administered CP (single infusion) plus SOC or SOC alone, and are to be followed for 30 days. The primary endpoint of the study is the proportion of patients that progress to categories 5, 6 or 7 (on the 7-point ordinal scale proposed by the WHO) at day 15. Interim analyses for efficacy and/or futility will be conducted once 20%, 40%, and 60% of the planned sample size are enrolled and complete D15 assessment. Discussion: This clinical trial is designed to evaluate the efficacy and safety of passive immunotherapy with convalescent plasma for the treatment of adult patients hospitalized with COVID-19. The results of this study are expected to contribute to establishing the potential place of CP in the therapeutics for a new viral disease. Trial registration: Trial registration at clinicaltrials.gov; Registration Number: NCT04345523; https://clinicaltrials.gov/ct2/show/NCT04345523; Registered on 30 March, 2020. First posted date: April 14, 2020. Keywords: COVID-19, randomized, controlled trial, protocol, convalescent plasma (CP), antibodies.

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Safety and Immunogenicity of Standard and Double Doses of Hepatitis B Vaccine in Children after Liver Transplantation: An Open-Label, Randomised Controlled Trial

Vaccines ◽

10.3390/vaccines10010092 ◽

2022 ◽

Vol 10 (1) ◽

pp. 92

Author(s):

Palittiya Sintusek ◽

Supranee Buranapraditkun ◽

Piyaporn Wanawongsawad ◽

Nawarat Posuwan ◽

Pattarawat Thantiworasit ◽

...

Keyword(s):

Liver Transplantation ◽

Hepatitis B ◽

De Novo ◽

Controlled Trial ◽

Geometric Mean ◽

Interferon Γ ◽

Specific Response ◽

Open Label ◽

High Prevalence ◽

Randomised Controlled

A high prevalence of hepatitis B (HepB) antibody loss after liver transplantation (LT) and de novo HepB infection (DNH) was documented, hence revaccination to prevent DNH is crucial. This study aimed to compare the safety and immunogenicity of two HepB vaccine regimens in liver-transplanted children. Liver-transplanted children who were previously immunised but showed HepB surface antibodies (anti-HBs) ≤ 100 mIU/mL were randomised to receive a standard three-dose (SD) and double three-dose (DD) vaccine intramuscularly in months 0–1–6. Anti-HBs and T-cell-specific response to the HepB antigen were assessed. A total of 61 children (54.1% male, aged 1.32 ± 1.02 years) completed the study without any serious adverse reaction. The seroprotective rate was 69.6% vs. 60% (p = 0.368) and 91.3% vs. 85% (p = 0.431) in SD and DD after the first and third 3-dose vaccinations, respectively. The geometric mean titre (95% confidence interval) of anti-HBs in SD and DD were 443.33 (200.75–979.07) vs. 446.17 (155.58–1279.50) mIU/mL, respectively, at completion. Numbers of interferon-γ-secreting cells were higher in hyporesponders/responders than in nonresponders (p = 0.003). The significant factors for the immunologic response to HepB vaccination were anti-HB levels prevaccination, tacrolimus trough levels, and time from LT to revaccination. SD and DD had comparative immunogenicity and were safe for liver-transplanted children who were previously immunised.

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Awake prone positioning of hypoxaemic patients with COVID-19: protocol for a randomised controlled open-label superiority meta-trial

BMJ Open ◽

10.1136/bmjopen-2020-041520 ◽

2020 ◽

Vol 10 (11) ◽

pp. e041520

Author(s):

Elsa Tavernier ◽

Bairbre McNicholas ◽

Ivan Pavlov ◽

Oriol Roca ◽

Yonatan Perez ◽

...

Keyword(s):

Controlled Trial ◽

Invasive Mechanical Ventilation ◽

Small Sample ◽

High Flow ◽

Occurrence Rate ◽

Prone Positioning ◽

Open Label ◽

Link Type ◽

Randomised Controlled ◽

Nasal High Flow Therapy

IntroductionProne positioning (PP) is an effective first-line intervention to treat patients with moderate to severe acute respiratory distress syndrome (ARDS) receiving invasive mechanical ventilation, as it improves gas exchanges and reduces mortality. The use of PP in awake spontaneous breathing patients with ARDS secondary to COVID-19 was reported to improve oxygenation in few retrospective trials with small sample size. High-level evidence of awake PP for hypoxaemic patients with COVID-19 patients is still lacking.Methods and analysisThe protocol of this meta-trial is a prospective collaborative individual participant data meta-analysis of randomised controlled open label superiority trials. This design is particularly adapted to a rapid scientific response in the pandemic setting. It will take place in multiple sites, among others in USA, Canada, Ireland, France and Spain. Patients will be followed up for 28 days. Patients will be randomised to receive whether awake PP and nasal high flow therapy or standard medical treatment and nasal high flow therapy. Primary outcome is defined as the occurrence rate of tracheal intubation or death up to day 28. An interim analysis plan has been set up on aggregated data from the participating research groups.Ethics and disseminationEthics approvals were obtained in all participating countries. Results of the meta-trial will be submitted for publication in a peer-reviewed journal. Each randomised controlled trial was registered individually, as follows: NCT04325906, NCT04347941, NCT04358939, NCT04395144 and NCT04391140.

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Post-intervention status in patients with refractory myasthenia gravis treated with eculizumab during REGAIN and its open-label extension

Neurology ◽

10.1212/wnl.0000000000011207 ◽

2020 ◽

pp. 10.1212/WNL.0000000000011207

Author(s):

Renato Mantegazza ◽

Gil I. Wolfe ◽

Srikanth Muppidi ◽

Heinz Wiendl ◽

Kenji P. Fujita ◽

...

Keyword(s):

Myasthenia Gravis ◽

Controlled Trial ◽

Open Label ◽

Post Intervention ◽

Open Label Study ◽

Label Study ◽

Link Type ◽

Open Label Extension ◽

Anti Acetylcholine

ObjectiveTo evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) to achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN and its open-label extension.MethodsPatients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study.ResultsA total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1–4.5). After 130 weeks of eculizumab treatment, 87.1% of patients achieved improved status and 57.1% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected.ConclusionsEculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population.Classification of evidenceThis study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo.Trial registrationREGAIN, NCT01997229; REGAIN open-label extension, NCT02301624 (ClinicalTrials.gov).

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Feasibility & Efficacy of Deprescribing rounds in a Singapore rehabilitative hospital- a randomised controlled trial

BMC Geriatrics ◽

10.1186/s12877-021-02507-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Andrew Peng Yong Wong ◽

Tan Wan Ting ◽

Ee Jia Ming Charissa ◽

Tan Wee Boon ◽

Kwan Yu Heng ◽

...

Keyword(s):

Randomised Controlled Trial ◽

Usual Care ◽

Multidisciplinary Team ◽

Controlled Trial ◽

Total Daily Dose ◽

Open Label ◽

Rehabilitation Hospital ◽

Link Type ◽

Randomised Controlled ◽

The Impact

Abstract Background Deprescribing is effective and safe in reducing polypharmacy among the elderly. However, the impact of deprescribing rounds remain unclear in Asian settings. Hence, we conducted this study. Methods An open label randomised controlled trial was conducted on patients of 65 years and above, under rehabilitation or subacute care and with prespecified medications from a Singapore rehabilitation hospital. They were randomised using a computer generated sequence. The intervention consisted of weekly multidisciplinary team-led deprescribing rounds (using five steps of deprescribing) and usual care. The control had only usual care. The primary outcome is the percentage change in total daily dose (TDD) from baseline upon discharge, while the secondary outcomes are the total number of medicine, total daily cost and TDD up to day 28 postdischarge, overall side-effect rates, rounding time and the challenges. Efficacy outcomes were analysed using intention-to-treat while other outcomes were analysed as per protocol. Results 260 patients were randomised and 253 were analysed after excluding dropouts (female: 57.3%; median age: 76 years). Baseline characteristics were largely similar in both groups. The intervention arm (n = 126) experienced a greater reduction of TDD on discharge [Median (IQR): − 19.62% (− 34.38, 0.00%) versus 0.00% (− 12.00, 6.82%); p < 0.001], more constipation (OR: 3.75, 95% CI:1.75–8.06, p < 0.001) and laxative re-prescriptions (OR: 2.82, 95% CI:1.30–6.12, p = 0.009) though death and hospitalisation rates were similar. The median rounding time was 7.09 min per patient and challenges include the inconvenience in assembling the multidisciplinary team. Conclusion Deprescribing rounds can safely reduce TDD of medicine upon discharge compared to usual care in a Singaporean rehabilitation hospital. Trial registration This study is first registered at Clinicaltrials.gov (protocol number: NCT03713112) on 19/10/2018 and the protocol can be accessed on https://www.clinicaltrials.gov.

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Pharmacist-guided pre-emptive pharmacogenetic testing in antidepressant therapy (PrePGx): study protocol for an open-label, randomized controlled trial

Trials ◽

10.1186/s13063-021-05724-5 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Céline K. Stäuble ◽

Markus L. Lampert ◽

Samuel Allemann ◽

Martin Hatzinger ◽

Kurt E. Hersberger ◽

...

Keyword(s):

Randomized Controlled Trial ◽

Antidepressant Treatment ◽

Controlled Trial ◽

Response Rates ◽

Control Group ◽

Open Label ◽

Randomized Controlled ◽

Link Type ◽

Increased Risk ◽

Antidepressant Pharmacotherapy

Abstract Background It is known that only 50% of patients diagnosed with major depressive disorders (MDD) respond to the first-line antidepressant treatment. Accordingly, there is a need to improve response rates to reduce healthcare costs and patient suffering. One approach to increase rates of treatment response might be the integration of pharmacogenetic (PGx) testing to stratify antidepressant drug selection. The goal of PGx assessments is to identify patients who have an increased risk to experience adverse drug reactions or non-response to specific drugs. Especially for antidepressants, there is compiling evidence on PGx influencing drug exposure as well as response. Methods This study is an open-label, randomized controlled trial conducted in two study centers in Switzerland: (1) the Psychiatric Clinic of Solothurn and (2) the Private Clinic Wyss in Münchenbuchsee. Adult inpatients diagnosed with a unipolar moderate or severe depressive episode are recruited at clinic admission and are included in the study. If the adjustment to a new antidepressant pharmacotherapy is necessary, the participants are randomized to either Arm A (intervention group) or Arm B (control group). If no new antidepressant pharmacotherapy is introduced the participants will be followed up in an observational arm. The intervention is the service of pharmacist-guided pre-emptive PGx testing to support clinical decision making on antidepressant selection and dosing. As a comparison, in the control group, the antidepressant pharmacotherapy is selected by the treating physician according to current treatment guidelines (standard of care) without the knowledge of PGx test results and support of clinical pharmacists. The primary outcome of this study compares the response rates under antidepressant treatment after 4 weeks between intervention and control arm. Discussion The findings from this clinical trial are expected to have a direct impact on inter-professional collaborations for the handling and use of PGx data in psychiatric practice. Trial registration ClinicalTrials.govNCT04507555. Registered on August 11, 2020. Swiss National Clinical Trials Portal SNCTP000004015. Registered August 18, 2020.

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Disulfiram repurposing combined with nutritional copper supplement as add-on to chemotherapy in recurrent glioblastoma (DIRECT): Study protocol for a randomized controlled trial

F1000Research ◽

10.12688/f1000research.16786.1 ◽

2018 ◽

Vol 7 ◽

pp. 1797 ◽

Cited By ~ 5

Author(s):

Asgeir Store Jakola ◽

Katja Werlenius ◽

Munila Mudaisi ◽

Sofia Hylin ◽

Sara Kinhult ◽

...

Keyword(s):

Randomized Controlled Trial ◽

Anticancer Agent ◽

Controlled Trial ◽

Progression Free Survival ◽

Preliminary Evidence ◽

Recurrent Glioblastoma ◽

Open Label ◽

Randomized Controlled ◽

Link Type ◽

Methylguanine Methyltransferase

Background: Disulfiram (DSF) is a well-tolerated, inexpensive, generic drug that has been in use to treat alcoholism since the 1950s. There is now independent preclinical data that supports DSF as an anticancer agent, and experimental data suggest that copper may increase its anti-neoplastic properties. There is also some clinical evidence that DSF is a promising anticancer agent in extracranial cancers. In glioblastoma, DSF induced O6-methylguanine methyltransferase (MGMT) inhibition may increase response to alkylating chemotherapy. A recent phase I study demonstrated the safety of DSF in glioblastoma patients when DSF was administered at doses below 500 mg/day together with chemotherapy. We plan to assess the effects of DSF combined with nutritional copper supplement (DSF-Cu) as an adjuvant to alkylating chemotherapy in glioblastoma treatment. Methods: In an academic, industry independent, multicenter, open label randomized controlled phase II/III trial with parallel group design (1:1) we will assess the efficacy and safety of DSF-Cu in glioblastoma treatment. The study will include 142 patients at the time of first recurrence of glioblastoma where salvage therapy with alkylating chemotherapy is planned. Patients will be randomized to treatment with or without DSF-Cu. Primary end-point is survival at 6 months. Secondary end-points are overall survival, progression free survival, quality of life, contrast enhancing tumor volume and safety. Discussion: There is a need to improve the treatment of recurrent glioblastoma. Results from this randomized controlled trial with DSF-Cu in glioblastoma will serve as preliminary evidence of the future role of DSF-Cu in glioblastoma treatment and a basis for design and power estimations of future studies. In this publication we provide rationale for our choices and discuss methodological issues. Trial registration: The study underwent registration in EudraCT 2016-000167-16 (Date: 30.03.2016,) and Clinicaltrials.gov NCT02678975 (Date: 31.01.2016) before initiating the study.

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Evaluation of Convalescent Plasma Versus Standard of Care for the Treatment of COVID-19 in Hospitalized Patients: study protocol for a phase 2 randomized, open-label, controlled, multicenter trial

10.21203/rs.3.rs-50154/v2 ◽

2020 ◽

Author(s):

Elena Diago-Sempere ◽

Aranzazu Sancho-López ◽

Jose Luis Bueno ◽

Elena Múñez-Rubio ◽

Ferran Torres ◽

...

Keyword(s):

Clinical Trial ◽

Respiratory Infections ◽

Controlled Trial ◽

Viral Disease ◽

Multicenter Trial ◽

Adult Patients ◽

Trial Registration ◽

Ordinal Scale ◽

Efficacy And Safety ◽

Open Label

Abstract Background: COVID-19 is a respiratory disease caused by a novel coronavirus (SARS-CoV-2) and causes substantial morbidity and mortality. At the time this clinical trial was planned, there were no available vaccine or therapeutic agents with proven efficacy, but the severity of the condition prompted the use of several pharmacological and non-pharmacological interventions. It has long been hypothesized that the use of convalescent plasma (CP) from infected patients who have developed an effective immune response is likely to be an option for the treatment of patients with a variety of severe acute respiratory infections (SARI) of viral etiology. The aim of this study is to assess the efficacy and safety of convalescent plasma in adult patients with severe COVID-19 pneumonia. Methods/Design: The ConPlas-19 study is a multicenter, randomized, open-label controlled trial. The study has been planned to include 278 adult patients hospitalized with severe COVID-19 infection not requiring mechanical ventilation (invasive or non-invasive). Subjects are randomly assigned in a 1:1 ratio (139 per treatment arm), stratified by center, to receive intravenously administered CP (single infusion) plus SOC or SOC alone, and are to be followed for 30 days. The primary endpoint of the study is the proportion of patients that progress to categories 5, 6 or 7 (on the 7-point ordinal scale proposed by the WHO) at day 15. Interim analyses for efficacy and/or futility will be conducted once 20%, 40%, and 60% of the planned sample size are enrolled and complete D15 assessment.Discussion: This clinical trial is designed to evaluate the efficacy and safety of passive immunotherapy with convalescent plasma for the treatment of adult patients hospitalized with COVID-19. The results of this study are expected to contribute to establishing the potential place of CP in the therapeutics for a new viral disease. Trial registration: Trial registration at clinicaltrials.gov; Registration Number: NCT04345523; https://clinicaltrials.gov/ct2/show/NCT04345523; Registered on 30 March, 2020. First posted date: April 14, 2020.

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