Proxalutamide Reduces the Rate of Hospitalization for COVID-19 Male Outpatients: A Randomized Double-Blinded Placebo-Controlled Trial

Antiandrogens have demonstrated a protective effect for COVOD-19 patients in observational and interventional studies. The goal of this study was to determine if proxalutamide, an androgen receptor antagonist, could be an effective treatment for men with COVID-19 in an outpatient setting. A randomized, double-blinded, placebo-controlled clinical trial was conducted at two outpatient centers (Brasilia, Brazil). Patients were recruited from October 21 to December 24, 2020 (clinicaltrials.gov number, NCT04446429). Male patients with confirmed COVID-19 but not requiring hospitalization (COVID-19 8-point ordinal scale <3) were administered proxalutamide 200 mg/day or placebo for up to 7 days. The primary endpoint was hospitalization rate at 30 days post-randomization. A total of 268 men were randomized in a 1:1 ratio. 134 patients receiving proxalutamide and 134 receiving placebo were included in the intention-to-treat analysis. The 30-day hospitalization rate was 2.2% in men taking proxalutamide compared to 26% in placebo, P < 0.001. The 30-day hospitalization risk ratio was 0.09; 95% confidence interval (CI) 0.03–0.27. Patients in the proxalutamide arm more frequently reported gastrointestinal adverse events, however, no patient discontinued treatment. In placebo group, 6 patients were lost during follow-up, and 2 patients died from acute respiratory distress syndrome. Here we demonstrate the hospitalization rate in proxalutamide treated men was reduced by 91% compared to usual care.

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Proxalutamide (GT0918) Reduces the Rate of Hospitalization and Death in COVID-19 Male Patients: A Randomized Double-Blinded Placebo-Controlled Trial.

10.21203/rs.3.rs-135303/v2 ◽

2021 ◽

Author(s):

John McCoy ◽

Andy Goren ◽

Flavio Adsuara Cadegiani ◽

Sergio Vaño-Galván ◽

Maja Kovacevic ◽

...

Keyword(s):

Controlled Trial ◽

Outpatient Setting ◽

Hospitalization Rate ◽

Ordinal Scale ◽

Controlled Clinical Trial ◽

Intention To Treat ◽

Androgen Receptor Antagonist ◽

Male Patients ◽

Double Blinded ◽

Lost To Follow Up

Abstract Background: Antiandrogens have demonstrated a protective effect for COVOD-19 patients in observational and interventional studies. The goal of this study was to determine if proxalutamide, an androgen receptor antagonist, could be an effective treatment for men with COVID-19 in an outpatient setting. Study design and methods: A randomized, double-blinded, placebo-controlled clinical trial was conducted at two outpatient centers (Brasilia, Brazil). Patients were recruited from October 21 to December 24, 2020 (ClinicalTrials.gov number, NCT04446429). Male patients with confirmed COVID-19 but not requiring hospitalization (COVID-19 8-point ordinal scale <3) were administered proxalutamide 200mg/day or placebo for up to 7 days. The primary endpoint was hospitalization rate at 30 days post-randomization.Results: A total of 268 men were randomized in a 1:1 ratio. 134 patients receiving proxalutamide and 134 receiving placebo were included in the intention-to-treat analysis. The 30-day hospitalization rate was 2.2% in men taking proxalutamide compared to 26% in placebo, P<0.001. The 30-day hospitalization risk ratio was 0.09; 95% confidence interval (CI) 0.03 to 0.27. Patients in the proxalutamide arm more frequently reported gastrointestinal adverse events, however, no patient discontinued treatment. In placebo group, 6 patients were lost to follow-up, and 2 patients died from acute respiratory distress syndrome.Conclusion: The hospitalization rate in proxalutamide treated men was reduced by 91% compared to usual care. Trial Registration: NCT04446429

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Proxalutamide (GT0918) Reduces the Rate of Hospitalization for COVID-19 Male Outpatients: A Randomized Double-Blinded Placebo-Controlled Trial.

10.21203/rs.3.rs-135303/v3 ◽

2021 ◽

Author(s):

John McCoy ◽

Andy Goren ◽

Flavio Adsuara Cadegiani ◽

Sergio Vaño-Galván ◽

Maja Kovacevic ◽

...

Keyword(s):

Controlled Trial ◽

Outpatient Setting ◽

Hospitalization Rate ◽

Ordinal Scale ◽

Controlled Clinical Trial ◽

Intention To Treat ◽

Androgen Receptor Antagonist ◽

Double Blinded ◽

Lost To Follow Up ◽

Design And Methods

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Tocilizumab in Hospitalized Patients With COVID-19 Pneumonia

10.1101/2020.08.27.20183442 ◽

2020 ◽

Cited By ~ 12

Author(s):

Ivan Rosas ◽

Norbert Bräu ◽

Michael Waters ◽

Ronaldo C. Go ◽

Bradley D. Hunter ◽

...

Keyword(s):

Hospital Discharge ◽

Controlled Trial ◽

Clinical Status ◽

Primary Outcome Measure ◽

Ordinal Scale ◽

Serious Adverse Events ◽

Intention To Treat ◽

Icu Stay ◽

Interleukin 6 Receptor ◽

Double Blinded

BACKGROUND COVID-19 is associated with immune dysregulation and hyperinflammation. Tocilizumab is an anti-interleukin-6 receptor antibody. METHODS Patients hospitalized with severe COVID-19 pneumonia receiving standard care were randomized (2:1) to double-blinded intravenous tocilizumab 8 mg/kg or placebo. The primary outcome measure was clinical status on a 7-category ordinal scale at day 28 (1, discharged/ready for discharge; 7, death). RESULTS Overall, 452 patients were randomized; the modified-intention-to-treat population included 294 tocilizumab-treated and 144 placebo-treated patients. Clinical status at day 28 was not statistically significantly improved for tocilizumab versus placebo (P=0.36). Median (95% CI) ordinal scale values at day 28: 1.0 (1.0 to 1.0) for tocilizumab and 2.0 (1.0 to 4.0) for placebo (odds ratio, 1.19 [0.81 to 1.76]). There was no difference in mortality at day 28 between tocilizumab (19.7%) and placebo (19.4%) (difference, 0.3% [95% CI, -7.6 to 8.2]; nominal P=0.94). Median time to hospital discharge was 8 days shorter with tocilizumab than placebo (20.0 and 28.0, respectively; nominal P=0.037; hazard ratio 1.35 [95% CI 1.02 to 1.79]). Median duration of ICU stay was 5.8 days shorter with tocilizumab than placebo (9.8 and 15.5, respectively; nominal P=0.045). In the safety population, serious adverse events occurred in 34.9% of 295 patients in the tocilizumab arm and 38.5% of 143 in the placebo arm. CONCLUSIONS In this randomized placebo-controlled trial in hospitalized COVID-19 pneumonia patients, tocilizumab did not improve clinical status or mortality. Potential benefits in time to hospital discharge and duration of ICU stay are being investigated in ongoing clinical trials.

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Probiotics Do Not Alter the Long-Term Stability of the Supragingival Microbiota in Healthy Subjects: A Randomized Controlled Trial

Pathogens ◽

10.3390/pathogens10040391 ◽

2021 ◽

Vol 10 (4) ◽

pp. 391

Author(s):

Christine Lundtorp-Olsen ◽

Christian Enevold ◽

Svante Twetman ◽

Daniel Belstrøm

Keyword(s):

Oral Health ◽

Controlled Trial ◽

Test Group ◽

External Perturbation ◽

Controlled Clinical Trial ◽

Healthy Individuals ◽

Compositional Stability ◽

Rdna Sequencing ◽

Double Blinded

Background: The purpose of the present study was to longitudinally characterize the supragingival microbiota throughout a three months period in orally healthy individuals. We tested the hypothesis that the supragingival microbiota shows a high degree of compositional stability, which is resilient against the external perturbation of regular use of probiotics, as long as oral health is maintained. Methods: The present study was a double-blinded, randomized, placebo-controlled clinical trial. The study population comprised a total of 110 oral and systemic healthy individuals, distributed in a probiotic (n = 55) and placebo (n = 55) group, where the test group consumed tablets with the probiotic strains Lacticaseibacillusrhamnosus (formerly Lactobacillus) PB01 DSM14870 and Latilactobacillus curvatus (formerly Lactobacillus) EB10 DSM32307 for a period of 12 weeks. Supragingival plaque samples and clinical registrations were performed at baseline, and after 4, 8, and 12 weeks, respectively. The supragingival microbiota was characterized by means of 16S rDNA sequencing. Sequences were referenced against the HOMD database. Results: No significant changes of the core microbiota, as expressed by relative abundance of predominant genera and species were evident during the three months observation period in the probiotic or the placebo group. Conclusions: Data from the present study clearly demonstrate long term compositional stability of the supragingival microbiota as long as oral health is maintained. In addition, the tested probiotics had no augmenting effect on the supragingival microbiota in oral health.

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Clinical Efficacy of Intra-articular Mesenchymal Stromal Cells for the Treatment of Knee Osteoarthritis: A Double-Blinded Prospective Randomized Controlled Clinical Trial

The American Journal of Sports Medicine ◽

10.1177/0363546519899923 ◽

2020 ◽

Vol 48 (3) ◽

pp. 588-598 ◽

Cited By ~ 12

Author(s):

Jaime R. Garza ◽

Richard E. Campbell ◽

Fotios P. Tjoumakaris ◽

Kevin B. Freedman ◽

Lawrence S. Miller ◽

...

Keyword(s):

Low Dose ◽

Controlled Trial ◽

Womac Score ◽

Percentage Change ◽

Controlled Clinical Trial ◽

High Dose ◽

Median Percentage ◽

Knee Oa ◽

Symptomatic Knee ◽

Double Blinded

Background: Currently, there are limited nonoperative treatment options available for knee osteoarthritis (OA). Cell-based therapies have emerged as promising treatments for knee OA. Autologous stromal vascular fraction (SVF) has been identified as an efficient medium for intra-articular administration of progenitor cells and mesenchymal stem cells derived from adipose tissue. Hypothesis: Patients receiving intra-articular SVF would show significantly greater improvement than patients receiving placebo injections, and this improvement would be dose dependent. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: This was a multisite prospective double-blinded randomized placebo-controlled clinical trial. Adult patients with symptomatic knee OA were eligible. Thirty-nine patients were randomized to high-dose SVF, low-dose SVF, or placebo (1:1:1). SVF was obtained via liposuction, processed to create the cellular implant, and injected during the same clinical visit. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores and magnetic resonance images were obtained preoperatively and at 6 and 12 months after injection. The Wilcoxon rank sum nonparametric test was utilized to assess statistical significance, and the Hodges-Lehmann location shift was used to assess superiority. Results: The median percentage change in WOMAC score at 6 months after injection for the high-dose, low-dose, and placebo groups was 83.9%, 51.5%, and 25.0%, respectively. The high- and low-dose groups had statistically significant changes in WOMAC scores when compared with the placebo group (high dose, P = .04; low dose, P = .02). The improvements were dose dependent. The median percentage change in WOMAC score from baseline to 1 year after injection for the high-dose, low-dose, and placebo groups was 89.5%, 68.2%, and 0%, respectively. The high- and low-dose groups displayed a greater percentage change at 12 months when compared with the placebo group (high dose, P = .006; low dose, P = .009). Magnetic resonance image review revealed no changes in cartilage thickness after treatment. No serious adverse events were reported. Conclusion: Intra-articular SVF injections can significantly decrease knee OA symptoms and pain for at least 12 months. The efficacy and safety demonstrated in this placebo-controlled trial support its implementation as a treatment option for symptomatic knee OA. Registration: NCT02726945 (ClinicalTrials.gov identifier)

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Levodopa+carbidopa in X-linked Dystonia Parkinsonism (XDP/DYT3/Lubag): A Randomized, Double-blind, Placebo-controlled Trial

Acta Medica Philippina ◽

10.47895/amp.v52i6.256 ◽

2018 ◽

Vol 52 (6) ◽

Author(s):

Roland Dominic G. Jamora ◽

Rosalia A. Teleg ◽

Cynthia P. Cordero ◽

Rodelyn F. Villareal-Jordan ◽

Lillian V. Lee ◽

...

Keyword(s):

Rating Scale ◽

Botulinum Toxin A ◽

Controlled Trial ◽

Controlled Clinical Trial ◽

Double Blind ◽

Efficacy Analysis ◽

Intention To Treat ◽

Oral Medications ◽

Significant Difference ◽

Scale Scores

Objective. X-linked dystonia parkinsonism (XDP) is an adult-onset, progressive and debilitating movement disorder described among Filipino males from Panay Island. The available oral medications have been ineffective. While chemodenervation with botulinum toxin A works and deep brain stimulation surgery is promising, these are not affordable for the vast majority of patients. Thus, we decided to look into the efficacy, safety and tolerability of levodopa+carbidopa (levodopa) versus placebo among patients with XDP. Methods. This was a double blind, randomized, placebo-controlled clinical trial. Patients were randomized to receive levodopa or placebo for 6 months. The dose was increased gradually until 1000 mg levodopa/day is reached or until side effects appear. Results. A total of 86 out of 94 randomized patients (91.5%) were included in the intention-to-treat cohort for the primary efficacy analysis. Nineteen patients (9 in levodopa, 10 in placebo) dropped out or were lost to follow up. There was no significant difference in the baseline and last visit Burke Fahn Marsden Dystonia Rating Scale and the part III of the Unified Parkinson’s Disease Rating Scale scores between levodopa and placebo. The most common adverse events in the levodopa group were increased movements, pain and nausea/ vomiting. Conclusion. While levodopa is safe and well-tolerated, it does not have any effect in alleviating the dystonia or parkinsonism in XDP

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Efficacy of colchicine in moderately symptomatic COVID-19 patients: a study protocol for a double-blind, randomized, placebo-controlled trial

International Journal of Clinical Trials ◽

10.18203/2349-3259.ijct20210144 ◽

2021 ◽

Vol 8 (1) ◽

pp. 43

Author(s):

Motlabur Rahman ◽

Mujibur Rahman ◽

Ponkaj K. Datta ◽

Khairul Islam ◽

Pratyay Hasan ◽

...

Keyword(s):

Standard Treatment ◽

Controlled Trial ◽

Ordinal Scale ◽

Controlled Clinical Trial ◽

Double Blind ◽

College Hospital ◽

Medical College ◽

The Status ◽

Anti Inflammatory ◽

Study Participants

Background: Inflammation is playing a major role in the pathophysiology of severe COVID-19 disease. The main causes of mortality are cytokine syndrome and immune thromboembolism. Colchicine is an anti-inflammatory drug but its action is mediated by completely different pathophysiologic routes than that of corticosteroids and non-steroidal anti-inflammatory agents. Colchicine inhibits neutrophil chemotaxis, inhibits inflammasome signaling and reduces interleukin-1β, reduces neutrophil-platelet interaction and aggregation. Colchicine is a readily available, cheap drug, has been used safely for many years. Specific targeted anti-inflammatory drugs like tocilizuma and anakinra are costly. A previous study suggested a significant clinical benefit from colchicine in patients hospitalized with COVID-19. But they did not compare with placebo. So, we have designed this study.Methods: This is a prospective, double-blind, randomized, placebo-controlled clinical trial. The study will be conducted at Dhaka medical college hospital, Bangladesh. Real time-polymerase chain reaction (RT-PCR) positive COVID-19 patients with moderate symptoms will be included in this study. Participants will be randomized into two groups at 1:1 ratio. Patients of one group will be treated with standard treatment along with colchicine for 14 days. The patients in other group will be treated with standard treatment along with placebo for the same duration. The primary outcome of the study will be time to develop clinical deterioration, defined as the time from randomization to a deterioration of two points (from the status at randomization) on a seven-category ordinal scale.Conclusions: Enrolment of participants has begun at the study site. A total of 300 participants will be enrolled.Trial Registration: ClinicalTrials.gov identifier: NCT04527562.

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Effectiveness of low-dose radiation therapy on symptoms in patients with knee osteoarthritis: a randomised, double-blinded, sham-controlled trial

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2018-214104 ◽

2018 ◽

pp. annrheumdis-2018-214104 ◽

Cited By ~ 12

Author(s):

Elien A M Mahler ◽

Michiel JM Minten ◽

Mathilde M Leseman-Hoogenboom ◽

Philip M P Poortmans ◽

Jan Willem H Leer ◽

...

Keyword(s):

Radiation Therapy ◽

Knee Osteoarthritis ◽

Low Dose ◽

Controlled Trial ◽

Controlled Clinical Trial ◽

Low Dose Radiation ◽

Knee Oa ◽

Sham Intervention ◽

Double Blinded ◽

Dose Radiation

ObjectivesLow-dose radiation therapy (LDRT) for benign disorders such as knee osteoarthritis (OA) is widely used in some parts of the world, despite absence of controlled studies. We evaluated the effect of LDRT on symptoms and inflammation in patients with knee OA.MethodsIn this randomised, double-blinded, sham-controlled clinical trial (RCT), we recruited patients with knee OA (clinical ACR criteria) in the Netherlands, aged ≥50 years, pain score ≥5/10 and non-responding to analgesics and exercise therapy. Patients were randomised 1:1 to receive LDRT (1 Gray per fraction) or sham intervention six times in 2 weeks, stratified by pain (<8 versus ≥8/10). Primary outcome was the proportion of OMERACT-OARSI responders, 3 months postintervention. Secondary outcomes included pain, function and inflammatory signs assessed by ultrasound, MRI and serum inflammatory markers.ResultsWe randomly assigned 55 patients: 27 (49%) to LDRT and 28 (51%) to sham. At 3 months postintervention, 12/27 patients (44%; 95% CI 26% to 63%) in the LDRT vs 12/28 patients (43%; 95% CI 25% to 61%) in the sham group responded; difference 2% (95% CI 25% to 28%), OR adjusted for the stratifying variable was 1.1 (95% CI 0.4 to 3.2). Also, for clinical and any of the inflammatory signs, no differences were observed.ConclusionsWe found no substantial beneficial effect on symptoms and inflammatory signs of LDRT in patients knee OA, compared with sham treatment. Therefore, based on this RCT and the absence of other high-quality evidence, we advise against the use of LDRT as treatment for knee OA.Trial registration numberNTR4574.

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The clinical and cost effectiveness of splints for thumb base osteoarthritis: a randomized controlled clinical trial

Rheumatology ◽

10.1093/rheumatology/keaa726 ◽

2020 ◽

Author(s):

Jo Adams ◽

Paula Barratt ◽

Ines Rombach ◽

Nigel Arden ◽

Sofia Barbosa Bouças ◽

...

Keyword(s):

Cost Effectiveness ◽

Controlled Trial ◽

Clinical Effectiveness ◽

Management Programme ◽

Self Management ◽

Controlled Clinical Trial ◽

Intention To Treat ◽

Randomized Controlled ◽

Hand Pain ◽

Parallel Group

Abstract Objectives To investigate the clinical effectiveness, efficacy and cost effectiveness of splints (orthoses) in people with symptomatic basal thumb joint OA (BTOA). Methods A pragmatic, multicentre parallel group randomized controlled trial at 17 National Health Service (NHS) hospital departments recruited adults with symptomatic BTOA and at least moderate hand pain and dysfunction. We randomized participants (1:1:1) using a computer-based minimization system to one of three treatment groups: a therapist supported self-management programme (SSM), a therapist supported self-management programme plus a verum thumb splint (SSM+S), or a therapist supported self-management programme plus a placebo thumb splint (SSM+PS). Participants were blinded to group allocation, received 90 min therapy over 8 weeks and were followed up for 12 weeks from baseline. Australian/Canadian (AUSCAN) hand pain at 8 weeks was the primary outcome, using intention to treat analysis. We calculated costs of treatment. Results We randomized 349 participants to SSM (n = 116), SSM+S (n = 116) or SSM+PS (n = 117) and 292 (84%) provided AUSCAN Osteoarthritis Hand Index hand pain scores at the primary end point (8 weeks). All groups improved, with no mean treatment difference between groups: SSM+S vs SSM −0.5 (95% CI: −1.4, 0.4), P = 0.255; SSM+PS vs SSM −0.1 (95% CI: −1.0, 0.8), P = 0.829; and SSM+S vs SSM+PS −0.4 (95% CI: −1.4, 0.5), P = 0.378. The average 12-week costs were: SSM £586; SSM+S £738; and SSM+PS £685. Conclusion There was no additional benefit of adding a thumb splint to a high-quality evidence-based, supported self-management programme for thumb OA delivered by therapists. Trial registration ISRCTN 54744256 (http://www.isrctn.com/ISRCTN54744256).

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Efficacy of Proxalutamide in Hospitalized COVID-19 Patients: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design Clinical Trial

10.1101/2021.06.22.21259318 ◽

2021 ◽

Author(s):

Flavio A Cadegiani ◽

Daniel N Fonseca ◽

John McCoy ◽

Ricardo A. Zimerman ◽

Fatima N Mirza ◽

...

Keyword(s):

Mechanical Ventilation ◽

Recovery Rate ◽

Clinical Status ◽

Primary Outcome Measure ◽

Ordinal Scale ◽

Recovery Ratio ◽

Double Blind ◽

Intention To Treat ◽

Androgen Receptor Antagonist ◽

All Cause Mortality

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectivity is mediated by the androgen-promoted protease, transmembrane protease, serine 2 (TMPRSS2). Previously, we have shown that treatment with proxalutamide, a non-steroidal androgen receptor antagonist, accelerates viral clearance and clinical remission in outpatients with coronavirus disease 2019 (COVID-19) compared to placebo. The effects in hospitalized COVID-19 patients were unknown. Methods: Men and women hospitalized but not requiring mechanical ventilation were randomized (1:1 ratio) to receive 300 mg of proxalutamide per day or placebo for 14 days. The study was conducted at eight sites in the state of Amazonas, Brazil. The primary outcome measure was the clinical status (8-point ordinal scale) at 14-days post-randomization. The primary efficacy endpoint was the 14-day recovery ratio (alive hospital discharge [scores 1, 2]). Findings: A total of 645 patients were randomized (317 received proxalutamide, 328 placebo) and underwent intention-to-treat analysis. The 14-day median ordinal scale score in the proxalutamide group was 1 (interquartile range [IQR]=1-2) versus 7 (IQR=2-8) for placebo, P<0.001. The 14-day recovery rate was 81.4% for proxalutamide and 35.7% for placebo (recovery ratio, 2.28; 95% CI 1.95-2.66 [P<0.001]). The 28-day all-cause mortality rate was 11.0% for proxalutamide versus 49.4% for placebo (hazard ratio, 0.16; 95% CI 0.11-0.24). The median post-randomization time to recovery was 5 days (IQR=3-8) for proxalutamide versus 10 days (IQR=6-15) for placebo. Interpretation: Hospitalized COVID-19 patients not requiring mechanical ventilation receiving proxalutamide had a 128% higher recovery rate than those treated with placebo. All-cause mortality was reduced by 77.7% over 28 days. (ClinicalTrials.gov number, NCT04728802).

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