scholarly journals Three day versus five day treatment with amoxicillin for non-severe pneumonia in young children: a multicentre randomised controlled trial

BMJ ◽  
2004 ◽  
Vol 328 (7443) ◽  
pp. 791 ◽  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Confidence Interval ◽  
Respiratory Rate ◽  
Day Treatment ◽  
Controlled Trial ◽  
Severe Pneumonia ◽  
Absolute Difference ◽  
Double Blind ◽  
Oral Amoxicillin ◽  
Syncytial Virus

AbstractObjective To assess the efficacy of three days versus five days of treatment with oral amoxicillin for curing non-severe pneumonia in children.Design Randomised, double blind, placebo controlled multicentre trial.Setting Outpatient departments of seven referral hospitals in India.Participants 2188 children aged 2-59 months, 1095 given three days of treatment and 1093 given five days.Intervention Oral amoxicillin 31-54 mg/kg/day in three divided doses.Main outcome measures Treatment failure: defined as development of chest indrawing, convulsions, drowsiness, or inability to drink at any time; respiratory rate above age specific cut points on day 3 or later; or oxygen saturation by pulse oximetry < 90% on day 3.Results The clinical cure rates with three days and five days of treatment were 89.5% and 89.9%, respectively (absolute difference 0.4 (95% confidence interval - 2.1 to 3.0)). Adherence to treatment regimen was 94% and 85% for three day and five day treatments, respectively. Loss to follow up was 5.4% by day 5. There were no deaths, 41 hospitalisations, and 36 minor adverse reactions. There were 225 (10.3%) clinical failures and 106 (5.3%) relapses, and rates were similar in both treatments. At enrolment, 513 (23.4%) children tested positive for respiratory syncytial virus, and Streptococcus pneumoniae and Haemophilus influenzae were isolated from the nasopharynx in 878 (40.4%) and 496 (22.8%) children, respectively. Clinical failure was associated with isolation of respiratory syncytial virus (adjusted odds ratio 1.95 (95% confidence interval 1.0 to 3.8)), excess respiratory rate of > 10 breaths/minute (2.89 (1.83 to 4.55)), and non-adherence with treatment at day 5 (11.57 (7.4 to 18.0)).Conclusions Treatment with oral amoxicillin for three days was as effective as for five days in children with non-severe pneumonia.

scholarly journals A Randomized, Placebo-Controlled, Respiratory Syncytial Virus Human Challenge Study of the Antiviral Efficacy, Safety, and Pharmacokinetics of RV521, an Inhibitor of the RSV-F Protein

2019 ◽  
Vol 64 (2) ◽  
Author(s):  
John DeVincenzo ◽  
Dereck Tait ◽  
John Efthimiou ◽  
Julie Mori ◽  
Young-In Kim ◽  
...  
Keyword(s):  
Viral Load ◽  
Respiratory Syncytial Virus ◽  
Adverse Events ◽  
Disease Severity ◽  
Controlled Trial ◽  
Primary Analysis ◽  
Double Blind ◽  
Challenge Virus ◽  
F Protein ◽  
Syncytial Virus

ABSTRACT Effective treatments for respiratory syncytial virus (RSV) infection are lacking. Here, we report a human proof-of-concept study for RV521, a small-molecule antiviral inhibitor of the RSV-F protein. In this randomized, double-blind, placebo-controlled trial, healthy adults were challenged with RSV-A Memphis-37b. After infection was confirmed (or 5 days after challenge virus inoculation), subjects received RV521 (350 mg or 200 mg) or placebo orally every 12 h for 5 days. The primary endpoint was area under the curve (AUC) for viral load, as assessed by reverse transcriptase quantitative PCR (RT-qPCR) of nasal wash samples. The primary efficacy analysis set included subjects successfully infected with RSV who received ≥1 dose of study drug. A total of 66 subjects were enrolled (n = 22 per group); 53 were included in the primary analysis set (RV521 350 mg: n = 16; 200 mg: n = 18; placebo: n = 19). The mean AUC of RT-qPCR-assessed RSV viral load (log10 PFU equivalents [PFUe]/ml · h) was significantly lower with RV521 350 mg (185.26; standard error [SE], 31.17; P = 0.002) and 200 mg (224.35; SE, 37.60; P = 0.007) versus placebo (501.39; SE, 86.57). Disease severity improved with RV521 350 mg and 200 mg versus placebo (P = 0.002 and P = 0.009, respectively, for AUC total symptom score [score × hours]). Daily nasal mucus weight was significantly reduced (P = 0.010 and P = 0.038 for RV521 350 mg and 200 mg, respectively, versus placebo). All treatment-emergent adverse events were grade 1 or 2. No subjects discontinued due to adverse events. There was no evidence of clinically significant viral resistance, and only three variants were detected. RV521 effectively reduced RSV viral load and disease severity in humans and was well tolerated. (This study has been registered at ClinicalTrials.gov under registration no. NCT03258502.)

scholarly journals Safety and Immunogenicity of the Respiratory Syncytial Virus Vaccine RSV/ΔNS2/Δ1313/I1314L in RSV-Seronegative Children

2019 ◽  
Vol 222 (1) ◽  
pp. 82-91 ◽  
Author(s):  
Ruth A Karron ◽  
Cindy Luongo ◽  
Jocelyn San Mateo ◽  
Kimberli Wanionek ◽  
Peter L Collins ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Rational Design ◽  
Controlled Trial ◽  
Geometric Mean ◽  
Neutralizing Antibody ◽  
Temperature Sensitive ◽  
Double Blind ◽  
Respiratory Tract Illness ◽  
Syncytial Virus ◽  
Respiratory Syncytial Virus Vaccine

Abstract Background Respiratory syncytial virus (RSV) is the leading global cause of severe pediatric acute respiratory tract illness, and a vaccine is needed. RSV/ΔNS2/Δ1313/I1314L contains 2 attenuating elements: (1) deletion of the interferon antagonist NS2 gene and (2) deletion of codon 1313 of the RSV polymerase gene and the stabilizing missense mutation I1314L. This live vaccine candidate was temperature-sensitive, genetically stable, replication restricted, and immunogenic in nonhuman primates. Methods A single intranasal dose of RSV/ΔNS2/Δ1313/I1314L was evaluated in a double-blind, placebo-controlled trial (vaccine-placebo ratio, 2:1) at 106 plaque-forming units (PFU) in 15 RSV-seropositive children and at 105 and 106 PFU in 21 and 30 RSV-seronegative children, respectively. Results In RSV-seronegative children, the 105 PFU dose was overattenuated, but the 106 PFU dose was well tolerated, infectious (RSV/ΔNS2/Δ1313/I1314L replication detected in 90% of vaccinees), and immunogenic (geometric mean serum RSV plaque-reduction neutralizing antibody titer, 1:64). After the RSV season, 9 of 20 vaccinees had increases in the RSV titer that were significantly greater than those in 8 of 10 placebo recipients (1:955 vs 1:69, respectively), indicating that the vaccine primed for anamnestic responses after natural RSV exposure. Conclusion Rational design yielded a genetically stable candidate RSV vaccine that is attenuated yet immunogenic in RSV-seronegative children, warranting further evaluation. Clinical Trials Registration NCT01893554.

Sign in / Sign up

Export Citation Format

Share Document