Peginterferon Lambda-1a for treatment of outpatients with uncomplicated COVID-19: a randomized placebo-controlled trial

AbstractType III interferons have been touted as promising therapeutics in outpatients with coronavirus disease 2019 (COVID-19). We conducted a randomized, single-blind, placebo-controlled trial (NCT04331899) in 120 outpatients with mild to moderate COVID-19 to determine whether a single, 180 mcg subcutaneous dose of Peginterferon Lambda-1a (Lambda) within 72 hours of diagnosis could shorten the duration of viral shedding (primary endpoint) or symptoms (secondary endpoint). In both the 60 patients receiving Lambda and 60 receiving placebo, the median time to cessation of viral shedding was 7 days (hazard ratio [HR] = 0.81; 95% confidence interval [CI] 0.56 to 1.19). Symptoms resolved in 8 and 9 days in Lambda and placebo, respectively, and symptom duration did not differ significantly between groups (HR 0.94; 95% CI 0.64 to 1.39). Both Lambda and placebo were well-tolerated, though liver transaminase elevations were more common in the Lambda vs. placebo arm (15/60 vs 5/60; p = 0.027). In this study, a single dose of subcutaneous Peginterferon Lambda-1a neither shortened the duration of SARS-CoV-2 viral shedding nor improved symptoms in outpatients with uncomplicated COVID-19.

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Peginterferon Lambda-1a for treatment of outpatients with uncomplicated COVID-19: a randomized placebo-controlled trial

10.21203/rs.3.rs-110659/v1 ◽

2020 ◽

Author(s):

Prasanna Jagannathan ◽

Jason Andrews ◽

Hector Bonilla ◽

Haley Hedlin ◽

Karen Jacobson ◽

...

Keyword(s):

Single Dose ◽

Confidence Interval ◽

Median Time ◽

Primary Endpoint ◽

Controlled Trial ◽

Hazard Ratio ◽

Secondary Endpoint ◽

Liver Transaminase ◽

Viral Shedding ◽

Subcutaneous Dose

Abstract Type III interferons have been touted as promising therapeutics in outpatients with coronavirus disease 2019 (COVID-19). We conducted a randomized placebo-controlled trial in 120 patients with mild to moderate COVID-19 to determine whether a single, 180 mcg subcutaneous dose of Peginterferon Lambda-1a (Lambda) could shorten the duration of viral shedding (primary endpoint) or symptoms (secondary endpoint, NCT04331899). In both the 60 patients receiving Lambda and 60 receiving placebo, the median time to cessation of viral shedding was 7 days (hazard ratio [HR] = 0.81; 95% confidence interval [CI] 0.56 to 1.19). Symptoms resolved in 8 and 9 days in Lambda and placebo, respectively (HR 0.94; 95% CI 0.64 to 1.39). At enrollment; 41% of subjects were SARS-CoV-2 IgG seropositive; compared to placebo, lambda tended to delay shedding cessation in seronegatives (aHR 0.66, 95% CI 0.39-1.10) and to hasten shedding cessation in seropositives (aHR 1.58, 95% CI 0.88-2.86; p for interaction = 0.03). Liver transaminase elevations were more common in the Lambda vs. placebo arm (15/60 vs 5/60; p = 0.027). In this study, a single dose of subcutaneous Peginterferon Lambda-1a neither shortened the duration of SARS-CoV-2 viral shedding nor improved symptoms in outpatients with uncomplicated COVID-19.

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Peginterferon Lambda-1a for treatment of outpatients with uncomplicated COVID-19: a randomized placebo-controlled trial

10.1101/2020.11.18.20234161 ◽

2020 ◽

Cited By ~ 1

Author(s):

Prasanna Jagannathan ◽

Jason R. Andrews ◽

Hector Bonilla ◽

Haley Hedlin ◽

Karen B. Jacobson ◽

...

Keyword(s):

Single Dose ◽

Confidence Interval ◽

Median Time ◽

Primary Endpoint ◽

Controlled Trial ◽

Hazard Ratio ◽

Secondary Endpoint ◽

Liver Transaminase ◽

Viral Shedding ◽

Subcutaneous Dose

AbstractType III interferons have been touted as promising therapeutics in outpatients with coronavirus disease 2019 (COVID-19). We conducted a randomized placebo-controlled trial in 120 patients with mild to moderate COVID-19 to determine whether a single, 180 mcg subcutaneous dose of Peginterferon Lambda-1a (Lambda) could shorten the duration of viral shedding (primary endpoint) or symptoms (secondary endpoint, NCT04331899). In both the 60 patients receiving Lambda and the 60 receiving placebo, the median time to cessation of viral shedding was 7 days (hazard ratio [HR] = 0.81; 95% confidence interval [CI] 0.56 to 1.19). Symptoms resolved in 8 and 9 days in Lambda and placebo, respectively (HR 0.94; 95% CI 0.64 to 1.39). At enrollment; 41% of subjects were SARS-CoV-2 IgG seropositive; compared to placebo, lambda tended to delay shedding cessation in seronegatives (aHR 0.66, 95% CI 0.39-1.10) and to hasten shedding cessation in seropositives (aHR 1.58, 95% CI 0.88-2.86; p for interaction = 0.03). Liver transaminase elevations were more common in the Lambda vs. placebo arm (15/60 vs 5/60; p = 0.027). In this study, a single dose of subcutaneous Peginterferon Lambda-1a neither shortened the duration of SARS-CoV-2 viral shedding nor improved symptoms in outpatients with uncomplicated COVID-19.

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A single dose of erythropoietin reduces perioperative transfusions in cardiac surgery: results of a prospective single-blind randomized controlled trial

Transfusion ◽

10.1111/trf.13027 ◽

2015 ◽

Vol 55 (7) ◽

pp. 1644-1654 ◽

Cited By ~ 48

Author(s):

Luca Weltert ◽

Beatrice Rondinelli ◽

Ricardo Bello ◽

Mauro Falco ◽

Alessandro Bellisario ◽

...

Keyword(s):

Randomized Controlled Trial ◽

Cardiac Surgery ◽

Single Dose ◽

Controlled Trial ◽

Randomized Controlled ◽

Single Blind

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Efficacy and cost-effectiveness of therapist-guided internet-delivered behaviour therapy for children and adolescents with Tourette syndrome: study protocol for a single-blind randomised controlled trial

10.31234/osf.io/rgycd ◽

2021 ◽

Author(s):

Per Andrén ◽

Lorena Fernández de la Cruz ◽

Kayoko Isomura ◽

Fabian Lenhard ◽

Charlotte L Hall ◽

...

Keyword(s):

Health Economic ◽

Primary Endpoint ◽

Controlled Trial ◽

Health Economic Evaluation ◽

Primary Objective ◽

Behaviour Therapy ◽

Tic Severity ◽

Randomised Controlled ◽

Single Blind

Background: Treatment guidelines recommend behaviour therapy (BT) for patients with Tourette syndrome (TS) and chronic tic disorder (CTD). However, BT is rarely accessible due to limited availability of trained therapists and long travel distances to specialist clinics. Internet-delivered BT has the potential of overcoming these barriers through remote delivery of treatment with minimal therapist support. In the current protocol, we outline the design and methods of a randomised controlled trial (RCT) evaluating an internet-delivered BT programme referred to as BIP TIC. The trial’s primary objective is to determine the clinical efficacy of BIP TIC for reducing tic severity in young people with TS/CTD, compared with an active control intervention. Secondary objectives are to investigate the 12-month durability of the treatment effects and to perform a health economic evaluation of the intervention.Methods: In this single-blind superiority RCT, 220 participants (9-17 years) with TS/CTD throughout Sweden will be randomised to 10-12 weeks of either therapist-supported internet-delivered BT based on exposure with response prevention (BIP TIC) or therapist-supported internet-delivered education. Data will be collected at baseline, 3 and 5 weeks into the treatment, at post-treatment, and 3, 6, and 12 months post-treatment. The primary endpoint is the 3-month follow-up. The primary outcome is tic severity as measured by the Yale Global Tic Severity Scale – Total tic severity score. Treatment response is operationalised as scores of “Very much improved” or “Much improved” on the Clinical Global Impression – Improvement scale, administered at the primary endpoint. Outcome assessors will be blind to treatment condition at all assessment points. A health economic evaluation of BIP TIC will be performed, both in the short term (primary endpoint) and the long term (12-month follow-up). There are no planned interim analyses. Discussion: Participant recruitment started on 26 April 2019 and finished on 9 April 2021. The final participant will reach the primary endpoint in September 2021 and the 12-month follow-up in June 2022. Data analysis for the primary objective will commence after the last participant reaches the primary endpoint.

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Intravenous Penciclovir for Treatment of Herpes Simplex Infections in Immunocompromised Patients: Results of a Multicenter, Acyclovir-Controlled Trial

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.43.5.1192 ◽

1999 ◽

Vol 43 (5) ◽

pp. 1192-1197 ◽

Cited By ~ 23

Author(s):

Hillard M. Lazarus ◽

Robert Belanger ◽

Anna Candoni ◽

Mickaël Aoun ◽

Regina Jurewicz ◽

...

Keyword(s):

Herpes Simplex ◽

Median Time ◽

Day Treatment ◽

Controlled Trial ◽

Complete Healing ◽

Double Blind ◽

Viral Shedding ◽

Hematologic Disorder ◽

Significant Difference ◽

Hsv Infections

ABSTRACT The efficacy and safety of penciclovir (PCV) for the treatment of herpes simplex virus (HSV) infections in immunocompromised (IC) patients were studied in a double-blind, acyclovir (ACV)-controlled, multicenter study. A total of 342 patients with mucocutaneous HSV infections received 5 mg of PCV per kg every 12 or 8 h (q12h or q8h) or 5 mg of ACV per kg q8h, beginning within 72 h of lesion onset and continuing for up to 7 days. The mean age of the patients was 49 years; 94% were white and 52% were female. The main reasons for their IC states were hematologic disorder (63%) and transplant plus hematologic disorder (16%). Clinical and virological assessments were performed daily during the 7-day treatment and then every other day until lesion healing. The primary efficacy parameter addressed new lesion formation. Secondary end points focused on viral shedding, healing, and pain. Approximately 20% of patients in each treatment group developed new lesions during therapy; thus, equivalence with ACV (defined prospectively) was demonstrated for both q12h and q8h PCV regimens. For all three treatment groups, the median time to the cessation of viral shedding was 4 days and the median time to complete healing was 8 days; there were no statistically significant differences in the rates of complete healing or the cessation of viral shedding when the results for PCV q12h and q8h were compared with those for ACV q8h. In addition, there was no statistically significant difference between PCV q12h or q8h, compared with ACV q8h, for the resolution of pain. PCV was well tolerated, with an adverse event profile comparable to that of ACV. In conclusion, PCV q12h is a well-tolerated and effective therapy for mucocutaneous HSV infection in IC patients and offers a reduced frequency of dosing compared with ACV q8h.

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A placebo-controlled double blind trial of hydroxychloroquine in mild-to-moderate COVID-19

10.1101/2020.10.19.20214940 ◽

2020 ◽

Cited By ~ 2

Author(s):

Vincent Dubée ◽

Pierre-Marie Roy ◽

Bruno Vielle ◽

Elsa Parot-Schinkel ◽

Odile Blanchet ◽

...

Keyword(s):

Primary Endpoint ◽

Controlled Trial ◽

Supplemental Oxygen ◽

Double Blind ◽

Intention To Treat ◽

Viral Shedding ◽

Virological Outcomes ◽

Secondary Endpoints ◽

To Receive ◽

Treat Population

AbstractBackgroundThe efficacy of hydroxychloroquine in coronavirus disease 2019 (COVID-19) remains controversial.MethodsWe conducted a multicentre randomized double-blind placebo-controlled trial evaluating hydroxychloroquine in COVID-19 patients with at least one of the following risk factors for worsening: age ≥75 years, age between 60 and 74 years, and presence of at least one comorbidity, or need for supplemental oxygen (≤3 L/min). Eligible patients were randomized in a 1:1 ratio to receive either 800mg hydroxychloroquine on Day 0 followed by 400mg per day for 8 days or a placebo. The primary endpoint was a composite of death or tracheal intubation within 14 days following randomization. Secondary endpoints included mortality and clinical evolution at Day 14 and 28, viral shedding at Day 5 and 10.ResultsThe trial was stopped after 250 patients were included due to a slowdown of the pandemic in France. The intention-to-treat population comprised 123 and 124 patients in the placebo and hydroxychloroquine groups, respectively. The median age was 77 years and 151 patients required oxygen therapy. The primary endpoint occurred in nine patients in the hydroxychloroquine group and eight patients in the placebo group (relative risk 1.12; 95% confidence interval 0.45– 2.80; P=0.82). No difference was observed between the two groups in any of the secondary endpoints.ConclusionIn this trial involving mainly older patients with mild-to-moderate COVID-19, patients treated with hydroxychloroquine did not experience better clinical or virological outcomes than those receiving the placebo.

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A Phase 2 randomized, double-blind, placebo-controlled trial of the monoclonal antibody MHAA4549A in patients with acute uncomplicated influenza A infection

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab630 ◽

2021 ◽

Author(s):

Jeremy J Lim ◽

Sadia Dar ◽

Dirk Venter ◽

Juan P Horcajada ◽

Priya Kulkarni ◽

...

Keyword(s):

Monoclonal Antibody ◽

Viral Load ◽

Median Time ◽

Influenza A ◽

Controlled Trial ◽

Human Monoclonal Antibody ◽

Phase 2 ◽

Double Blind ◽

Double Blind Placebo ◽

Viral Shedding

Abstract Background MHAA4549A, a human monoclonal antibody targeting the influenza A hemagglutinin stalk, neutralizes influenza A virus in animal and human volunteer challenge studies. We investigated MHAA4549A safety and tolerability, efficacy, and pharmacokinetics in outpatients with acute, uncomplicated influenza A infection. Methods This was a Phase 2, randomized, double-blind, placebo-controlled trial of single intravenous (IV) doses of 3600 mg or 8400 mg MHAA4549A, or IV placebo in adult outpatients testing positive for influenza A. Patients were enrolled across 35 sites in 6 countries. Randomization and dosing occurred ≤ 72 hours of symptom onset; study duration was 14 weeks. The primary endpoint was the nature and frequency of adverse events (AEs). Secondary endpoints included median time to alleviation of all influenza symptoms, effects on nasopharyngeal viral load and duration of viral shedding, and MHAA4549A serum pharmacokinetics. Results Of 125 randomized patients, 124 received study treatment, with 99 confirmed positive for influenza A by central testing. Frequency of AEs between MHAA4549A and placebo groups was similar; nausea was most common (8 patients; 6.5%). MHAA4549A serum exposure was confirmed in all MHAA4549A-treated patients and was dose proportional. No hospitalizations or deaths occurred. Between MHAA4549A and placebo groups, no statistically significant differences occurred in median time to alleviation of all symptoms, nasopharyngeal viral load, or duration of viral shedding. Conclusions While MHAA4549A was safe and well-tolerated with confirmed exposure, the antibody did not improve clinical outcomes in patients with acute uncomplicated influenza A infection.

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Dynamic Lycra® orthoses as an adjunct to arm rehabilitation after stroke: a single-blind, two-arm parallel group, randomized controlled feasibility trial

Clinical Rehabilitation ◽

10.1177/0269215519840403 ◽

2019 ◽

Vol 33 (8) ◽

pp. 1331-1343 ◽

Cited By ~ 3

Author(s):

Jacqui H Morris ◽

Alexandra John ◽

Lucy Wedderburn ◽

Petra Rauchhaus ◽

Peter T Donnan

Keyword(s):

Randomized Controlled Trial ◽

Action Research ◽

Confidence Interval ◽

Odds Ratio ◽

Adverse Reactions ◽

Controlled Trial ◽

Randomized Controlled ◽

Arm Rehabilitation ◽

Parallel Group ◽

Single Blind

Objective: The aim of this study was to explore the feasibility of conducting a randomized controlled trial of dynamic Lycra® orthoses as an adjunct to arm rehabilitation after stroke and to explore the magnitude and direction of change on arm outcomes. Design: This is a single-blind, two-arm parallel group, feasibility randomized controlled trial. Setting: In-patient rehabilitation. Subjects: The study participants were stroke survivors with arm hemiparesis two to four weeks after stroke receiving in-patient rehabilitation. Interventions: Participants were randomized 2:1 to wear Lycra® gauntlets for eight hours daily for eight weeks, plus usual rehabilitation ( n = 27), or to usual rehabilitation only ( n = 16). Main measures: Recruitment, retention, fidelity, adverse events and completeness of data collection were examined at 8 and 16 weeks; arm function (activity limitation; Action Research Arm Test, Motor Activity Log) and impairment (Nine-hole Peg Test, Motricity Index, Modified Tardieu Scale). Structured interviews explored acceptability. Results: Of the target of 51, 43 (84%) participants were recruited. Retention at 8 weeks was 32 (79%) and 24 (56%) at 16 weeks. In total, 11 (52%) intervention group participants and 6 (50%) control group participants (odds ratio = 1.3, 95% confidence interval = 0.2 to 7.8) had improved Action Research Arm Test level by 8 weeks; at 16 weeks, this was 8 (61%) intervention and 6 (75.0%) control participants (odds ratio = 1.1, 95% confidence interval = 0.1 to 13.1). Change on other measures favoured control participants. Acceptability was influenced by 26 adverse reactions. Conclusion: Recruitment and retention were low, and adverse reactions were problematic. There were no indications of clinically relevant effects, but the small sample means definitive conclusions cannot be made. A definitive trial is not warranted without orthoses adaptation.

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Antipyretic efficacy and tolerability of oral ibuprofen, oral dipyrone and intramuscular dipyrone in children: a randomized controlled trial

Sao Paulo Medical Journal ◽

10.1590/s1516-31802006000300005 ◽

2006 ◽

Vol 124 (3) ◽

pp. 135-140 ◽

Cited By ~ 6

Author(s):

Judith Prado ◽

Raúl Daza ◽

Oscar Chumbes ◽

Iván Loayza ◽

Luis Huicho

Keyword(s):

Single Dose ◽

Primary Outcome ◽

Controlled Trial ◽

Emergency Ward ◽

Over The Counter ◽

Randomized Controlled ◽

Associated Symptoms ◽

Oral Ibuprofen ◽

To Receive ◽

Single Blind

CONTEXT AND OBJECTIVE: Dipyrone is a widely used over-the-counter antipyretic in Latin America, and elsewhere among Latin immigrants. Despite limited evidence, physicians often prescribe oral ibuprofen or intramuscular dipyrone as the most effective antipyretics. Our aim was to compare the antipyretic efficacy and tolerability of a single dose of oral ibuprofen, oral dipyrone or intramuscular dipyrone in febrile children. DESIGN AND SETTING: Randomized, single-blind clinical trial, at San Bartolomé Mother-Child National Teaching Hospital, Lima, Peru. METHODS: Children from six months to six years old with fever (rectal temperature: 38.3 to 39.8° C) in the emergency ward between February and June 2003 were eligible. Seventy-five children were randomly assigned to receive a single dose of oral ibuprofen (10 mg/kg), oral dipyrone (15 mg/kg) or intramuscular dipyrone (15 mg/kg). The primary outcome was mean temperature reduction after 30, 45, 60, 90 and 120 minutes. Secondary outcomes were fever-associated symptoms and clinical adverse events. RESULTS: Fever decreased by about 0.5° C after 45 minutes and by about 1.0° C after 120 minutes in all three groups. Mean temperatures were similar for the three groups at all times. There was a significant decrease in fever-associated symptoms for all groups. Six patients (four receiving oral dipyrone and two receiving ibuprofen) were withdrawn because of vomiting within 20 minutes after first dose of study medication. One patient assigned to oral ibuprofen presented transient urticaria. CONCLUSIONS: Antipyretic efficacy and tolerability were similar for oral ibuprofen, oral dipyrone and intramuscular dipyrone. Oral antipyretics seem more appropriate for feverish children.

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Efficacy and cost-effectiveness of therapist-guided internet-delivered behaviour therapy for children and adolescents with Tourette syndrome: study protocol for a single-blind randomised controlled trial

Trials ◽

10.1186/s13063-021-05592-z ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Per Andrén ◽

Lorena Fernández de la Cruz ◽

Kayoko Isomura ◽

Fabian Lenhard ◽

Charlotte L. Hall ◽

...

Keyword(s):

Health Economic ◽

Primary Endpoint ◽

Controlled Trial ◽

Health Economic Evaluation ◽

Primary Objective ◽

Behaviour Therapy ◽

Tic Severity ◽

Randomised Controlled ◽

Single Blind

Abstract Background Treatment guidelines recommend behaviour therapy (BT) for patients with Tourette syndrome (TS) and chronic tic disorder (CTD). However, BT is rarely accessible due to limited availability of trained therapists and long travel distances to specialist clinics. Internet-delivered BT has the potential of overcoming these barriers through remote delivery of treatment with minimal therapist support. In the current protocol, we outline the design and methods of a randomised controlled trial (RCT) evaluating an internet-delivered BT programme referred to as BIP TIC. The trial’s primary objective is to determine the clinical efficacy of BIP TIC for reducing tic severity in young people with TS/CTD, compared with an active control intervention. Secondary objectives are to investigate the 12-month durability of the treatment effects and to perform a health economic evaluation of the intervention. Methods In this single-blind superiority RCT, 220 participants (9–17 years) with TS/CTD throughout Sweden will be randomised to 10–12 weeks of either therapist-supported internet-delivered BT based on exposure with response prevention (BIP TIC) or therapist-supported internet-delivered education. Data will be collected at baseline, 3 and 5 weeks into the treatment, at post-treatment, and 3, 6, and 12 months post-treatment. The primary endpoint is the 3-month follow-up. The primary outcome is tic severity as measured by the Yale Global Tic Severity Scale – Total Tic Severity Score. Treatment response is operationalised as scores of “Very much improved” or “Much improved” on the Clinical Global Impression – Improvement scale, administered at the primary endpoint. Outcome assessors will be blind to treatment condition at all assessment points. A health economic evaluation of BIP TIC will be performed, both in the short term (primary endpoint) and the long term (12-month follow-up). There are no planned interim analyses. Discussion Participant recruitment started on 26 April 2019 and finished on 9 April 2021. The total number of included participants was 221. The final participant is expected to reach the primary endpoint in September 2021 and the 12-month follow-up in June 2022. Data analysis for the primary objective will commence after the last participant reaches the primary endpoint. Trial registration ClinicalTrials.gov NCT03916055. Registered on 16 April 2019.

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