scholarly journals 5-Alpha-Reductase Inhibitors Reduce Remission Time of COVID-19: Results From a Randomized Double Blind Placebo Controlled Interventional Trial in 130 SARS-CoV-2 Positive Men

2020 ◽  
Author(s):  
Flávio Adsuara Cadegiani ◽  
John McCoy ◽  
Carlos Gustavo Wambier ◽  
Andy Goren
Keyword(s):  
Nasal Congestion ◽  
Cohort Analysis ◽  
Group Versus ◽  
Outpatient Setting ◽  
Nasal Discharge ◽  
Double Blind ◽  
Runny Nose ◽  
Reductase Inhibitors ◽  
5 Alpha Reductase Inhibitors ◽  
Total Remission

BackgroundSARS-CoV-2 entry into type II pneumocytes is depended on the TMPRSS2 proteolytic enzyme. The only known promoter of TMPRSS2 in humans is an androgen response element. As such, androgen sensitivity may be a risk factor for COVID-19. Previously, we have reported a retrospective cohort analysis demonstrating the protective effect of 5-alpha-reductase inhibitors (5ARis) in COVID-19. Men using 5ARis were less likely to be admitted to the ICU than men not taking 5ARis. Additionally, men using 5ARis had drastically reduced frequency of symptoms compared to men not using 5ARis in an outpatient setting. Here we aim to determine if 5ARis will be a beneficial treatment if given after SARS-CoV-2 infection.MethodsA double-blinded, randomized, prospective, investigational study of dutasteride for the treatment of COVID-19 (NCT04446429). Subjects confirmed positive for SARS-CoV-2 were treated in an outpatient setting. Endpoints for the study were remission times for a predetermined set of symptoms: fever or feeling feverish, cough, shortness of breath, sore throat, body pain or muscle pain/ache, fatigue, headache, nasal congestion, nasal discharge (runny nose), nausea or vomiting, diarrhea, loss of appetite, and loss of taste or smell (Ageusia or Anosmia).ResultsA total of 130 SARS-CoV-2 positive men were included in the study, 64 subjects in the dutasteride arm and 66 subjects in the placebo-controlled group. The differences in the average remission times for fatigue and anosmia or ageusia was statistically different between the groups (5.8 versus 10.1 days for fatigue and 7.3 versus 13.4 days for anosmia or ageusia, in dutasteride and placebo groups, respectively), however, the total remission time was significantly reduced for the men given dutasteride; 9.0 days versus 15.6 days in the placebo group (p < 0.001). Excluding loss of taste and smell the average total remission time was 7.3 days in the dutasteride group versus 11.7 in the placebo arm (p < 0.001).ConclusionThe total remission time for men using 5ARis was significantly reduced compared to men not taking 5ARis.

scholarly journals Phase II, Randomized, Double-Blind, Placebo-Controlled Studies of Ruprintrivir Nasal Spray 2-Percent Suspension for Prevention and Treatment of Experimentally Induced Rhinovirus Colds in Healthy Volunteers

2003 ◽  
Vol 47 (12) ◽  
pp. 3907-3916 ◽  
Author(s):  
Frederick G. Hayden ◽  
Ronald B. Turner ◽  
Jack M. Gwaltney ◽  
Kathy Chi-Burris ◽  
Merril Gersten ◽  
...  
Keyword(s):  
Treatment Group ◽  
Healthy Volunteers ◽  
Group Versus ◽  
Placebo Treatment ◽  
Pharmacokinetic Analysis ◽  
Nasal Discharge ◽  
Double Blind ◽  
Placebo Treatment Group ◽  
Double Blind Placebo ◽  
Viral Titers

ABSTRACT Human rhinovirus (HRV) infections are usually self-limited but may be associated with serious consequences, particularly in those with asthma and chronic respiratory disease. Effective antiviral agents are needed for preventing and treating HRV illnesses. Ruprintrivir (Agouron Pharmaceuticals, Inc., San Diego, Calif.) selectively inhibits HRV 3C protease and shows potent, broad-spectrum anti-HRV activity in vitro. We conducted three double-blind, placebo-controlled clinical trials in 202 healthy volunteers to assess the activity of ruprintrivir in experimental HRV infection. Subjects were randomized to receive intranasal ruprintrivir (8 mg) or placebo sprays as prophylaxis (two or five times daily [2×/day or 5×/day] for 5 days) starting 6 h before infection or as treatment (5×/day for 4 days) starting 24 h after infection. Ruprintrivir prophylaxis reduced the proportion of subjects with positive viral cultures (for 5×/day dosing groups, 44% for ruprintrivir treatment group versus 70% for placebo treatment group [P = 0.03]; for 2×/day dosing groups, 60% for ruprintrivir group versus 92% for placebo group [P = 0.004]) and viral titers but did not decrease the frequency of colds. Ruprintrivir treatment reduced the mean total daily symptom score (2.2 for ruprintrivir treatment group and 3.3 for the placebo treatment group [P = 0.014]) by 33%. Secondary endpoints, including viral titers, individual symptom scores, and nasal discharge weights, were also reduced by ruprintrivir treatment. Overall, ruprintrivir was well tolerated; blood-tinged mucus and nasal passage irritation were the most common adverse effects reported. Pharmacokinetic analysis of plasma and nasal ruprintrivir concentrations revealed intranasal drug residence with minimal systemic absorption. Results from these studies in experimental rhinoviral infection support continued investigation of intranasal ruprintrivir in the setting of natural HRV infection.

scholarly journals Evaluation of Montelukast for the Treatment of Children With Japanese Cedar Pollinosis Using an Artificial Exposure Chamber (OHIO Chamber)

2018 ◽  
Vol 9 ◽  
pp. 215265671878359 ◽  
Author(s):  
Kazuhiro Hashiguchi ◽  
Kimihiro Okubo ◽  
Yoichi Inoue ◽  
Hirotaka Numaguchi ◽  
Kumi Tanaka ◽  
...  
Keyword(s):  
Day Treatment ◽  
Nasal Congestion ◽  
Placebo Response ◽  
Japanese Cedar ◽  
Nasal Symptom ◽  
Exposure Chamber ◽  
Nasal Discharge ◽  
Japanese Children ◽  
Double Blind ◽  
Pollen Exposure

Background This study evaluated the efficacy of montelukast in reducing seasonal allergic rhinitis symptoms in Japanese children with Japanese cedar (JC) pollinosis induced in an artificial exposure chamber (OHIO Chamber). Methods Pediatric patients aged 10 to 15 years sensitive to JC pollen entered a randomized, double-blind, single-site, crossover study. After confirmation of an allergic response to a JC pollen exposure for 3 hours in the OHIO Chamber during the screening period, subjects received either montelukast 5 mg chewable tablets or placebo for a 7-day treatment period, followed by a 3-hour pollen exposure in the chamber. After a 7-day washout period, subjects crossed over to the other treatment. Subjects were instructed to self-assess their nasal symptoms using 5-point scale for every 30 minutes. The primary end point was the change from baseline (just before entering the exposure chamber for each exposure) in total nasal symptom score (TNSS; the sum of nasal congestion, nasal discharge, and sneezing scores) over 3 hours of pollen exposure. Adverse events (AEs) were evaluated throughout the study. Results A total of 220 subjects (median age, 12 years) received treatment. For TNSS, the between-group difference in the change (95% confidence interval) was −0.01 (−0.11 to 0.10); the change between placebo and montelukast 5 mg was not significant. TNSS in the screening and treatment periods after receiving placebo for 7 days was 1.58 and 1.31, respectively, suggesting a placebo response. On account of high placebo response, a post hoc analysis was conducted. The analysis in a subgroup of subjects who did not show placebo response demonstrated a difference in the efficacy between montelukast and placebo (nominal P < .037). The most common AE was positive urine protein (4.6% with montelukast vs 7.8% with placebo). Conclusions Although montelukast was well tolerated, this study did not demonstrate a treatment difference between active drug and placebo in Japanese children exposed to JC pollen in the OHIO Chamber. Trial Registry: ClinicalTrials.gov, NCT01852812

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

2020 ◽  
Author(s):  
Flavio Adsuara Cadegiani ◽  
John McCoy ◽  
Carlos Gustavo Wambier ◽  
Maja Kovacevic ◽  
Jerry Shapiro ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Cohort Analysis ◽  
Group Versus ◽  
Standard Of Care ◽  
Time Frame ◽  
Ordinal Scale ◽  
Control Group ◽  
Androgen Treatment ◽  
Reductase Inhibitors ◽  
Double Blinded

Abstract Importance: Previously, we have reported a retrospective cohort analysis demonstrating the protective effect of anti-androgens (5-alpha-reductase inhibitors) in COVID-19. Objective: To determine if the anti-androgen proxalutimide is an effective treatment for men with ambulatory mild COVID-19 disease.Design: A double-blinded, randomized, prospective, investigational study of proxalutamide for the treatment men with ambulatory mild COVID-19 disease.Setting: Outpatient centers (Brasilia, Brazil) from July 15 to December 1, 2020. Participants: Men with ambulatory mild COVID-19 disease (WHO ordinal scale ≤3).Interventions: Proxalutimide 200mg/day, or standard of care for 30 days or until full COVID-19 remission. Main Outcome and Measures: Percentage of subjects hospitalized due to COVID-19 [Time Frame: 30 days].Results: A total of 214 men were included and completed the trial; 114 men were randomized to the proxalutamide group, and 100 men were randomized to the control group. A statistically significant reduction in the percentage of subjects hospitalized due to COVID-19 was observed in men taking proxalutamide (0%) compared to the standard of care (27%), (p<0.001). The percentage of men requiring mechanical ventilation was reduced in the proxalutamide group (0%) compared to control (9%), (p<0.001). Zero fatalities occurred in the proxalutamide group, versus 2 in the control group.Conclusions and Relevance: Men with ambulatory mild COVID-19 disease (WHO ordinal scale ≤3) receiving anti-androgen treatment with proxalutamide, had significantly reduced rate of hospitalization compared to men not receiving anti-androgen treatment. Trial Registration: NCT04446429

scholarly journals Low Dose, Short-Term Oral Methylprednisolone for Nasal Polyps: A Randomized Double-Blind Placebo-Controlled Trial

2006 ◽  
Vol 21 (1-2) ◽  
pp. 24-27
Author(s):  
Romeo C. Sanchez ◽  
Benjamin SA. Campomanes ◽  
Natividad A. Aguilar
Keyword(s):  
Nasal Polyps ◽  
Nasal Polyposis ◽  
Low Dose ◽  
Nasal Congestion ◽  
Controlled Trial ◽  
Group Versus ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Nasal Symptoms ◽  
Postnasal Drip

Objectives: To determine the efficacy of a 7-day treatment of methylprednisolone 16mg in reducing the size of nasal polyps and on improvement of nasal symptoms.   Methods: Design: Randomized double-blind placebo-controlled trial Setting: Out-patient department of the East Avenue Medical Center Patients: Patients 18 years old and above with nasal polyposis determined by history and endoscopic examination   Results: There was a significant decrease in polyp size by an average of 16% (P < .05) among 12 out of the 23 patients (52.17 %) in the steroid group versus placebo. The treatment group also exhibited an improvement in nasal symptoms of rhinorrhea, congestion and anosmia compared to the placebo.   Conclusion: Medical treatment with oral methylprednisolone given at a low dose of 16 mg for one week resulted in reduction of the size of nasal polyps and improved the symptoms of rhinorrhea, nasal congestion and anosmia. Other associated symptoms like headache, epistaxis,  sneezing, itchiness, epiphora, cough, postnasal drip, throat discomfort, facial pain, eye complaints and fever did not differ between the steroid and placebo groups.   Recommendation: One week of oral steroids can be used to treat nasal polyps initially. If there is response, this mode of management can be combined with a long-term course of intranasal steroid sprays9,10. Patients who do not respond may be referred for surgery.   Keywords: Nasal polyposis, methylprednisolone, rhinorrhea, nasal congestion, anosmia  

scholarly journals Sexual Dysfunctions Related to Drugs Used in the Management of Lower Urinary Tract Symptoms Due to Benign Prostatic Hyperplasia: A Narrative Review on α-Blockers and 5-Alpha Reductase Inhibitors

Uro ◽  
2021 ◽  
Vol 1 (3) ◽  
pp. 82-98
Author(s):  
Antonio La Torre ◽  
Caterina Palleria ◽  
Irene Tamanini ◽  
Andrea Scardigli ◽  
Tommaso Cai ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Benign Prostatic Hyperplasia ◽  
Sexual Dysfunction ◽  
Lower Urinary Tract ◽  
Prostatic Hyperplasia ◽  
Sexual Dysfunctions ◽  
Reductase Inhibitors ◽  
Urinary Tract Symptoms ◽  
5 Alpha Reductase Inhibitors ◽  
Lower Urinary

This is a critical review of the current literature data about sexual dysfunction as a potential side effect related to drugs commonly used for the treatment of Benign Prostatic Hyperplasia and Lower Urinary Tract Symptoms. In this narrative review, we analyzed data from the literature related to the development of sexual dysfunctions during the treatment of BPH or LUTS. Both α-blockers and 5-alpha reductase inhibitors (5-ARIs) can induce erectile dysfunction, ejaculatory disorders and a reduction in sexual desire. The sexual side effect profile of these drugs is different. Among the α-blockers, silodosin appears to have the highest incidence of ejaculatory disorders. Persistent sexual side effects after the discontinuation of finasteride have been recently reported; however, further studies are needed to clarify the true incidence and the significance of this finding. However, most of the published studies are affected by a weak methodology and other important limitations, with only a few RCTs available. Therefore, it is desirable that future studies will include validated tools to assess and diagnose the sexual dysfunction induced by these medications, especially for ejaculation and sexual desire disorders.

scholarly journals 4-Azasteroidal 5 alpha-reductase inhibitors without affinity for the androgen receptor.

1984 ◽  
Vol 259 (2) ◽  
pp. 734-739
Author(s):  
T Liang ◽  
C E Heiss ◽  
A H Cheung ◽  
G F Reynolds ◽  
G H Rasmusson
Keyword(s):  
Androgen Receptor ◽  
Reductase Inhibitors ◽  
5 Alpha Reductase Inhibitors

scholarly journals Efficacy and Safety of Oritavancin Relative to Vancomycin for Patients with Acute Bacterial Skin and Skin Structure Infections (ABSSSI) in the Outpatient Setting: Results From the SOLO Clinical Trials

2017 ◽  
Vol 4 (1) ◽  
Author(s):  
Thomas P. Lodise ◽  
Mark Redell ◽  
Shannon O. Armstrong ◽  
Katherine A. Sulham ◽  
G. Ralph Corey
Keyword(s):  
Clinical Trials ◽  
Composite Endpoint ◽  
Outpatient Setting ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Double Blind ◽  
Skin Structure ◽  
Efficacy Outcome ◽  
End Of Treatment ◽  
Secondary Endpoints

Abstract Background The objective of this analysis was to evaluate the efficacy and safety of oritavancin compared with vancomycin for patients with acute bacterial skin and skin structure infections (ABSSSIs) who received treatment in the outpatient setting in the Phase 3 SOLO clinical trials. Methods SOLO I and SOLO II were 2 identically designed comparative, multicenter, double-blind, randomized studies to evaluate the efficacy and safety of a single 1200-mg dose of intravenous (IV) oritavancin versus 7–10 days of twice-daily IV vancomycin for the treatment of ABSSSI. Protocols were amended to allow enrolled patients to complete their entire course of antimicrobial therapy in an outpatient setting. The primary efficacy outcome was a composite endpoint (cessation of spread or reduction in size of the baseline lesion, absence of fever, and no rescue antibiotic at early clinical evaluation [ECE]) (48 to 72 hours). Key secondary endpoints included investigator-assessed clinical cure 7 to 14 days after end of treatment (posttherapy evaluation [PTE]) and 20% or greater reduction in lesion area at ECE. Safety was assessed until day 60. Results Seven hundred ninety-two patients (oritavancin, 392; vancomycin, 400) received entire course of treatment in the outpatient setting. Efficacy response rates at ECE and PTE were similar (primary composite endpoint at ECE: 80.4% vs 77.5% for oritavancin and vancomycin, respectively) as was incidence of adverse events. Five patients (1.3%) who received oritavancin and 9 (2.3%) vancomycin patients were subsequently admitted to a hospital. Conclusions Oritavancin provides a single-dose alternative to multidose vancomycin for treatment of ABSSSI in the outpatient setting.

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