scholarly journals Safety and efficacy of antiviral therapy alone or in combination in COVID-19 - a randomized controlled trial (SEV COVID Trial)

2021 ◽  
Author(s):  
◽  
Prasan Kumar Panda
Keyword(s):  
Randomized Controlled Trial ◽  
Standard Treatment ◽  
Therapeutic Potential ◽  
Controlled Trial ◽  
Antiviral Treatment ◽  
Severe Disease ◽  
Open Label ◽  
Drug Induced ◽  
Randomized Controlled ◽  
Severe Group

Background Definitive antiviral treatment is not available for COVID-19 infection except remdesivir that even with many doubts. Various combination antivirals have been tried. Methods A single-center, open-label, parallel-arm, stratified randomized controlled trial evaluated the therapeutic potential of hydroxychloroquine and lopinavir-ritonavir in combination with ribavirin in COVID-19. Enrolled patients in severe category were randomized into three groups: A: standard treatment, B: hydroxychloroquine+ribavirin+standard treatment, or C: lopinavir+ritonavir+ribavirin+standard treatment; while non-severe category into two groups: A: standard treatment or B: hydroxychloroquine+ribavirin. Combination antivirals was given for 10 days and followed for 28 days. The primary endpoints were safety, symptomatic and laboratory recovery of organ dysfunctions, and time to SARS-CoV-2 RT-PCR negative report. Results Total 111 patients randomized: 24, 23, and 24 in severe category A, B, and C respectively, and 20 in each non-severe group. Two patients receiving ribavirin experienced drug induced liver injury and another developed QT prolongation after hydroxychloroquine. In the severe category, 47.6%, 55%, and 30.09% in A, B, and C groups respectively showed symptomatic recovery compared to 93.3% and 86.7% in A and B groups respectively in the non-severe category at 72hrs (P>0.05). Conclusions The results failed to show statistical superiority of the antiviral combination therapies to that of the standard therapy in both the severe and non-severe categories in symptomatic adult patients of COVID-19. However, results do indicate the benefit of non-standard interventional combination therapy in severe disease. Furthermore, the dose of ribavirin needs to be reconsidered in the Indian population.

scholarly journals An open label randomized controlled trial of tamoxifen combined with amphotericin B and fluconazole for cryptococcal meningitis

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Nguyen Thi Thuy Ngan ◽  
Nhat Thanh Hoang Le ◽  
Nguyen Ngo Vi Vi ◽  
Ninh Thi Thanh Van ◽  
Nguyen Thi Hoang Mai ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Cryptococcal Meningitis ◽  
Standard Care ◽  
Therapeutic Potential ◽  
Controlled Trial ◽  
High Dose ◽  
Open Label ◽  
Randomized Controlled ◽  
Cancer Agent

Background: Cryptococcal meningitis has high mortality. Flucytosine is a key treatment but is expensive and rarely available. The anti-cancer agent tamoxifen has synergistic anti-cryptococcal activity with amphotericin in vitro. It is off-patent, cheap, and widely available. We performed a trial to determine its therapeutic potential.Methods:Open label randomized controlled trial. Participants received standard care - amphotericin combined with fluconazole for the first two weeks - or standard care plus tamoxifen 300mg/day. The primary end point was Early Fungicidal Activity (EFA) - the rate of yeast clearance from cerebrospinal fluid (CSF). Trial registration https://clinicaltrials.gov/ct2/show/NCT03112031 .Results: 50 patients were enrolled, (median age 34 years, 35 male). Tamoxifen had no effect on EFA (- 0.48log10 colony-forming units/mL/CSF control arm versus -0.49 tamoxifen arm, difference - 0.005log10CFU/ml/day, 95%CI: -0.16, 0.15, P=0.95). Tamoxifen caused QTc prolongation.Conclusion: High dose tamoxifen does not increase the clearance rate of Cryptococcus from CSF. Novel, affordable therapies are needed.Funding:The trial was funded through the Wellcome Trust Asia Programme Vietnam Core Grant 106680 and a Wellcome Trust Intermediate Fellowship to JND grant number WT097147MA.

scholarly journals Convalescent plasma in the management of moderate COVID-19 in India: An open-label parallel-arm phase II multicentre randomized controlled trial (PLACID Trial)

2020 ◽  
Author(s):  
Anup Agarwal ◽  
Aparna Mukherjee ◽  
Gunjan Kumar ◽  
Pranab Chatterjee ◽  
Tarun Bhatnagar ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Phase Ii ◽  
Neutralizing Antibodies ◽  
Therapeutic Option ◽  
Controlled Trial ◽  
Severe Disease ◽  
Real Life ◽  
Open Label ◽  
Randomized Controlled ◽  
And Control

Objectives: Convalescent plasma (CP) as a passive source of neutralizing antibodies and immunomodulators is a century-old therapeutic option used for the management of viral diseases. We investigated its effectiveness for the treatment of COVID-19. Design: Open-label, parallel-arm, phase II, multicentre, randomized controlled trial. Setting: Thirty-nine public and private hospitals across India. Participants: Hospitalized, moderately ill confirmed COVID-19 patients (PaO2/FiO2: 200-300 or respiratory rate > 24/min and SpO2 ≤ 93% on room air). Intervention: Participants were randomized to either control (best standard of care (BSC)) or intervention (CP + BSC) arm. Two doses of 200 mL CP was transfused 24 hours apart in the intervention arm. Main Outcome Measure: Composite of progression to severe disease (PaO2/FiO2<100) or all-cause mortality at 28 days post-enrolment. Results: Between 22 nd April to 14 th July 2020, 464 participants were enrolled; 235 and 229 in intervention and control arm, respectively. Composite primary outcome was achieved in 44 (18.7%) participants in the intervention arm and 41 (17.9%) in the control arm [aOR: 1.09; 95% CI: 0.67, 1.77]. Mortality was documented in 34 (14.5%) and 31 (13.5%) participants in intervention and control arm, respectively [aOR) 1.06 95% CI: 0.61 to 1.83]. Interpretation: CP was not associated with reduction in mortality or progression to severe COVID-19. This trial has high generalizability and approximates real-life setting of CP therapy in settings with limited laboratory capacity. A priori measurement of neutralizing antibody titres in donors and participants may further clarify the role of CP in management of COVID-19.

Standard versus sequential anti-tubercular treatment in patients with tuberculous meningitis: a randomized controlled trial

2020 ◽  
Author(s):  
Usha Kant Misra ◽  
Mritunjai Kumar ◽  
Jayantee Kalita
Keyword(s):  
Randomized Controlled Trial ◽  
Hospital Mortality ◽  
Tuberculous Meningitis ◽  
Controlled Trial ◽  
Hospital Death ◽  
Inclusion Criteria ◽  
Open Label ◽  
Drug Induced ◽  
Standard Regimen ◽  
Randomized Controlled

Abstract Background To compare the safety and efficacy of sequential anti-tubercular treatment (ATT) regimen with the standard regimen in tuberculous meningitis (TBM). Methods This single-centre, open-label, parallel group randomized controlled trial was conducted from May 2017 to June 2019 in India. Treatment-naïve patients with TBM fulfilling the inclusion criteria were randomized to four drug ATT regimens (rifampicin, isoniazid, ethambutol and pyrazinamide) administered either simultaneously (standard arm) or one after another (sequential arm) in a 1 : 1 ratio. The primary endpoint was drug-induced hepatitis (DIH) and the secondary endpoints were in-hospital death and disability at 3 and 6 months using a modified Rankin Scale. Results A total of 97 patients with TBM were recruited; 15 did not meet the inclusion criteria and 2 refused to participate. The median age of the patients was 26 y (range 15–75) and 37 (46.2%) were males. The patients in the sequential arm had fewer cases of DIH (20% vs 42.5%; p=0.03). The patients in the sequential arm had lower in-hospital mortality (2.5% vs 17.5%; p=0.025) and better 6-month outcomes (25.0% vs 50.0%; p=0.02) compared with the standard arm. Conclusions Sequential ATT was associated with a lower frequency of DIH, lower in-hospital mortality and better 6-month outcome. Trial registration Clinical Trials Registry of India (ctri.nic.in) identifier: REF/2016/09/012214/CTRI/2017/10/010072.

scholarly journals Clinical and functional connectivity outcomes of 5-Hz repeated transcranial magnetic stimulation as an add-on treatment in cocaine use disorder: a double-blind randomized controlled trial

2020 ◽  
Author(s):  
Eduardo A. Garza-Villarreal ◽  
Ruth Alcala-Lozano ◽  
Sofia Fernandez-Lozano ◽  
Erik Morelos-Santana ◽  
Alan Dávalos ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Functional Connectivity ◽  
Standard Treatment ◽  
Controlled Trial ◽  
Angular Gyrus ◽  
Adjunctive Treatment ◽  
Open Label ◽  
Double Blind ◽  
Cocaine Use ◽  
Randomized Controlled

AbstractBACKGROUNDCocaine use disorder (CUD) is a global condition lacking effective treatment. Repeated magnetic transcranial stimulation (rTMS) may reduce craving and frequency of cocaine use, but little is known about its efficacy and neural effects.OBJECTIVE/HYPOTHESISWe sought to elucidate short- and long-term clinical benefits of 5-Hz rTMS as an add-on to standard treatment in CUD patients and discern underlying functional connectivity (FC) effects using magnetic resonance imaging.METHODSForty-four CUD patients were randomly assigned to complete the 2-week double-blind randomized controlled trial (acute phase) [Sham (n=20, 2 female) and Active (n=24, 4 female)], in which they received 2 daily sessions of rTMS on the left dorsolateral prefrontal cortex. Subsequently, 20 CUD patients continued to an open-label maintenance phase for 6 months (2 weekly sessions for up to 6 months).RESULTSrTMS plus standard treatment for 2 weeks significantly reduced craving (p = 0.013, d=0.77) and impulsivity (p = 0.011, d=0.79) in the Active group. We also found increased FC between lDLPFC-vmPFC and vmPFC-right angular gyrus Clinical and functional connectivity effects were maintained for 3 months but they dissipated by 6 months. We did not observe reduction of positive cocaine urine tests, however, self-reported frequency and grams consumed for 6 months were reduced.CONCLUSIONSWith this RCT we show that 5-Hz rTMS has potential promise as an adjunctive treatment for CUD and merits further research.

Investigating the Impact of Cognitive Training for Individuals With Bothersome Tinnitus: A Randomized Controlled Trial

2021 ◽  
pp. 019459982199474
Author(s):  
Maggie Xing ◽  
Dorina Kallogjeri ◽  
Jay F. Piccirillo
Keyword(s):  
Randomized Controlled Trial ◽  
Cognitive Training ◽  
Mixed Model ◽  
Controlled Trial ◽  
Intervention Group ◽  
Control Group ◽  
Functional Index ◽  
Open Label ◽  
Randomized Controlled ◽  
The Impact

Objective To evaluate the effectiveness of cognitive training in improving tinnitus bother and to identify predictors of patient response. Study Design Prospective open-label randomized controlled trial. Setting Online. Methods Participants were adults with subjective idiopathic nonpulsatile tinnitus causing significant tinnitus-related distress. The intervention group trained by using auditory-intensive exercises for 20 minutes per day, 5 days per week, for 8 weeks. The active control group trained on the same schedule with non–auditory intensive games. Surveys were completed at baseline, 8 weeks, and 12 weeks. Results A total of 64 participants completed the study. The median age was 63 years (range, 25-69) in the intervention group and 61 years (34-68) in the control group. Mixed model analysis revealed that within-subject change in Tinnitus Functional Index in the intervention group was not different than the control group, with marginal mean differences (95% CI): 0.24 (–11.20 to 10.7) and 2.17 (–8.50 to 12.83) at 8 weeks and 2.33 (–8.6 to 13.3) and 3.36 (–7.91 to 14.6) at 12 weeks, respectively. When the 2 study groups were compared, the control group had higher Tinnitus Functional Index scores than the intervention group by 10.5 points at baseline (95% CI, –0.92 to 29.89), 8.1 at 8 weeks (95% CI, –3.27 to 19.42), and 9.4 at 12 weeks (95% CI, –2.45 to 21.34). Conclusion Auditory-intensive cognitive training was not associated with changes in self-reported tinnitus bother. Given the potential for neuroplasticity to affect tinnitus, we believe that future studies on cognitive training for tinnitus remain relevant.

Sign in / Sign up

Export Citation Format

Share Document