PLoS clinical trials最新文献

{"title":"The influence of injection rate on the hypnotic effect of propofol during anesthesia: a randomized trial.","authors":"Jasmin Blum,&nbsp;Eberhard Kochs,&nbsp;Nicole Forster,&nbsp;Gerhard Schneider","doi":"10.1371/journal.pctr.0010017","DOIUrl":"https://doi.org/10.1371/journal.pctr.0010017","url":null,"abstract":"<p><strong>Objective: </strong>Previous studies suggested that slow injection of propofol may increase the hypnotic effect during induction of anesthesia. The aim of the present study was therefore to investigate whether injection rate of propofol has an influence on its maximum effect.</p><p><strong>Design: </strong>Randomized, single-blind trial.</p><p><strong>Setting: </strong>This study has been carried out in the operating rooms of a university hospital. An anesthesiologist and a resident performed the study with the aid of changing nursing staff.</p><p><strong>Participants: </strong>We investigated 99 unpremedicated patients aged 18 to 60 years with American Society of Anesthesiologists (ASA) physical status 1-3.</p><p><strong>Interventions: </strong>Anesthesia was induced by intravenous injection of propofol (2 mg/kg). Propofol was manually injected in group 1 over a period of 5 s; in group 2 (120-s injection interval), and in group 3 (240-s injection interval), propofol was administered by an injection pump. After loss of consciousness, mask ventilation was performed with 100% oxygen. Bispectral index (BIS) was used to measure the hypnotic effect of propofol. After the decrease of BIS to the minimum value (i.e., maximum hypnotic effect) and the following increase of BIS to 60, the study period was finished and anesthesia was performed according to clinical criteria.</p><p><strong>Outcome measures: </strong>We analyzed whether injection speed has an influence on the maximum hypnotic effect of a given dose of propofol (2 mg/kg).</p><p><strong>Results: </strong>BIS(min) marks the maximum electroencephalogram (EEG) effect of the propofol bolus as measured by the BIS. The lowest mean BIS(min) was measured in group 1 (28.7 +/- 10.3). In group 2, BIS(min) was 33.0 (+/-13.9), and in group 3, BIS(min) was 36.4 (+/-11.0). There were no significant differences between group 2 and groups 1 or 3, but there were significant differences between groups 1 and 3. In group 1, BIS(min) was reached after 102.91 s (+/-44.20), in group 2 after 172.33 s (+/-29.76), and in group 3 after 274.21 s (+/-45.40). These differences were statistically significant for all comparisons. In summary, the lowest value for BIS(min) was achieved in the group with the fastest rate of propofol injection (group1, 5 s). The highest BIS(min) was obtained in the group with the slowest rate of injection (group 3, 240 s). The hemodynamic parameters were not significantly different among groups.</p><p><strong>Conclusions: </strong>The hypnotic peak effect of propofol is lower with extremely slow injection (240 s versus 5 s). For clinically usual injection rates (5 s and 120 s), there was no significant difference in propofol peak effect.</p>","PeriodicalId":87416,"journal":{"name":"PLoS clinical trials","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1371/journal.pctr.0010017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26173447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A randomised trial comparing genotypic and virtual phenotypic interpretation of HIV drug resistance: the CREST study.","authors":"Gillian Hales,&nbsp;Chris Birch,&nbsp;Suzanne Crowe,&nbsp;Cassy Workman,&nbsp;Jennifer F Hoy,&nbsp;Matthew G Law,&nbsp;Anthony D Kelleher,&nbsp;Douglas Lincoln,&nbsp;Sean Emery","doi":"10.1371/journal.pctr.0010018","DOIUrl":"https://doi.org/10.1371/journal.pctr.0010018","url":null,"abstract":"<p><strong>Objectives: </strong>The aim of this study was to compare the efficacy of different HIV drug resistance test reports (genotype and virtual phenotype) in patients who were changing their antiretroviral therapy (ART).</p><p><strong>Design: </strong>Randomised, open-label trial with 48-week followup.</p><p><strong>Setting: </strong>The study was conducted in a network of primary healthcare sites in Australia and New Zealand.</p><p><strong>Participants: </strong>Patients failing current ART with plasma HIV RNA > 2000 copies/mL who wished to change their current ART were eligible. Subjects were required to be > 18 years of age, previously treated with ART, have no intercurrent illnesses requiring active therapy, and to have provided written informed consent.</p><p><strong>Interventions: </strong>Eligible subjects were randomly assigned to receive a genotype (group A) or genotype plus virtual phenotype (group B) prior to selection of their new antiretroviral regimen.</p><p><strong>Outcome measures: </strong>Patient groups were compared for patterns of ART selection and surrogate outcomes (plasma viral load and CD4 counts) on an intention-to-treat basis over a 48-week period.</p><p><strong>Results: </strong>Three hundred and twenty seven patients completing >or= one month of followup were included in these analyses. Resistance tests were the primary means by which ART regimens were selected (group A: 64%, group B: 62%; p = 0.32). At 48 weeks, there were no significant differences between the groups for mean change from baseline plasma HIV RNA (group A: 0.68 log copies/mL, group B: 0.58 log copies/mL; p = 0.23) and mean change from baseline CD4+ cell count (group A: 37 cells/mm(3), group B: 50 cells/mm(3); p = 0.28).</p><p><strong>Conclusions: </strong>In the absence of clear demonstrated benefits arising from the use of the virtual phenotype interpretation, this study suggests resistance testing using genotyping linked to a reliable interpretive algorithm is adequate for the management of HIV infection.</p>","PeriodicalId":87416,"journal":{"name":"PLoS clinical trials","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1371/journal.pctr.0010018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26173446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chloroquine/sulphadoxine-pyrimethamine for gambian children with malaria: transmission to mosquitoes of multidrug-resistant Plasmodium falciparum.","authors":"Rachel L Hallett, Samuel Dunyo, Rosalynn Ord, Musa Jawara, Margaret Pinder, Anna Randall, Ali Alloueche, Gijs Walraven, Geoffrey A T Targett, Neal Alexander, Colin J Sutherland","doi":"10.1371/journal.pctr.0010015","DOIUrl":"10.1371/journal.pctr.0010015","url":null,"abstract":"<p><strong>Objectives: </strong>In the Gambia, chloroquine (CQ) plus sulphadoxine-pyrimethamine (SP) is the first-line antimalarial treatment. Plasmodium falciparum parasites carrying mutations associated with resistance to each of these drugs were present in 2001 but did not cause a significant loss of therapeutic efficacy among children receiving the combination CQ/SP. We measured their effect on parasite transmission to Anopheles gambiae mosquitoes.</p><p><strong>Design: </strong>We conducted a single-blind, randomised, controlled trial with follow-up over 28 d. Mosquito feeding experiments were carried out 7, 10, or 14 d after treatment.</p><p><strong>Setting: </strong>The study took place in the town of Farafenni and surrounding villages in the Gambia.</p><p><strong>Participants: </strong>Participants were 500 children aged 6 mo to 10 y with uncomplicated P. falciparum malaria.</p><p><strong>Interventions: </strong>Children were randomised to receive CQ, SP, or CQ/SP.</p><p><strong>Outcome measures: </strong>Outcomes related to transmission were determined, including posttreatment gametocyte prevalence and density. Infectiousness was assessed by membrane-feeding A. gambiae mosquitoes with blood from 70 gametocyte-positive patients. Mutations at seven loci in four genes associated with drug resistance were measured pre- and posttreatment and in the midguts of infected mosquitoes.</p><p><strong>Results: </strong>After SP treatment, the infectiousness of gametocytes was delayed, compared to the other two treatment groups, despite comparable gametocyte densities. Among bloodmeal gametocytes and the midguts of infected mosquitoes, the presence of the four-locus multidrug-resistant haplotype TYRG (consisting of mutations pfcrt-76T, pfmdr1-86Y, pfdhfr-59R, and pfdhps-437G) was associated with significantly higher oocyst burdens after treatment with the combination CQ/SP.</p><p><strong>Conclusions: </strong>Parasites with a multidrug-resistant genotype had a substantial transmission advantage after CQ/SP treatment but did not have a significant impact on in vivo efficacy of this drug combination. Protocols that include measuring transmission endpoints as well as therapeutic outcomes may be a useful strategy when monitoring the evolution of drug resistance in malaria parasites in vivo.</p>","PeriodicalId":87416,"journal":{"name":"PLoS clinical trials","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1513405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26168000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Randomised trial of chloroquine/sulphadoxine-pyrimethamine in Gambian children with malaria: impact against multidrug-resistant P. falciparum.","authors":"Samuel Dunyo, Rosalynn Ord, Rachel Hallett, Musa Jawara, Gijs Walraven, Eduardo Mesa, Rosalind Coleman, Maimuna Sowe, Neal Alexander, Geoffrey A T Targett, Margaret Pinder, Colin J Sutherland","doi":"10.1371/journal.pctr.0010014","DOIUrl":"10.1371/journal.pctr.0010014","url":null,"abstract":"<p><strong>Objectives: </strong>In the Gambia, the combination of chloroquine (CQ) and sulphadoxine-pyrimethamine (SP) has replaced CQ monotherapy for treatment of malaria caused by Plasmodium falciparum. We measured the efficacy of the combination CQ/SP, and the prevalence of parasites carrying alleles associated with resistance to CQ or SP.</p><p><strong>Design: </strong>We conducted a single-blind, randomised, controlled trial to compare the efficacy of CQ/SP to that of SP or CQ alone.</p><p><strong>Setting: </strong>The study took place in the town of Farafenni and surrounding villages in the Gambia.</p><p><strong>Participants: </strong>Participants were children aged 12 mo to 10 y presenting as outpatients with uncomplicated P. falciparum malaria.</p><p><strong>Interventions: </strong>500 children were randomised to receive CQ, SP, or CQ/SP as supervised treatment and actively followed over 28 d.</p><p><strong>Outcome measures: </strong>Primary outcome was parasitaemia at any time during follow-up. Secondary outcomes were PCR-confirmed recrudescent infections among treatment failures, and clinical failure requiring rescue medication by day 28. Pretreatment parasite isolates from 161 patients were tested for the presence of resistance-associated genetic markers.</p><p><strong>Results: </strong>The prevalence of parasitological failure by day 28 for the CQ group was 60.3%, compared to 17.6% for SP (odds ratio [OR], 0.106; 95% confidence interval [CI], 0.057-0.194; p < 0.001) and 13.9% for CQ/SP (OR versus CQ, 0.140; 95% CI, 0.078-0.250; p < 0.001). There was no difference between the SP and CQ/SP groups (OR, 1.324; 95% CI, 0.705-2.50). The projected prevalence of PCR-corrected treatment failure was 30.2, 6.06, and 3.94% in the CQ, SP, and CQ/SP groups, respectively. The pfdhfr-triple mutant and pfdhps-437G mutation were common, with prevalences of 67.4 and 51.2%, respectively. Pretreatment carriage of pfdhps-437G and of multidrug-resistant parasite genotypes was associated with treatment failure in the SP group, but not in the CQ or CQ/SP groups.</p><p><strong>Conclusions: </strong>The combination of CQ/SP was an efficacious treatment for uncomplicated malaria in Gambian children in this study, but the frequent occurrence of multidrug-resistant parasites suggests that this observed efficacy is not sustainable.</p>","PeriodicalId":87416,"journal":{"name":"PLoS clinical trials","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1513406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26167365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Operational challenges in large clinical trials: examples and lessons learned from the gambia pneumococcal vaccine trial.","authors":"Felicity T Cutts,&nbsp;Godwin Enwere,&nbsp;Syed M A Zaman,&nbsp;Fred G Yallop","doi":"10.1371/journal.pctr.0010016","DOIUrl":"https://doi.org/10.1371/journal.pctr.0010016","url":null,"abstract":"The requirements for Good Clinical Practice (GCP) in clinical trials are well documented [1], and ethical issues are hotly debated [2]. Operational aspects of trials, however, have received far less attention [3], perhaps due to restrictions on journal space for detailing methods. In low resource settings, however, large trials often face many logistical and organizational obstacles, and thus the practical difficulties in running a trial to GCP standards should not be ignored. Here, we describe the main operational challenges to a randomized, double-blind, placebo-controlled trial of the safety and efficacy of pneumococcal conjugate vaccine among over 17,000 infants in the Gambia. The trial began in August 2000, and after the magnitude of the challenges were recognized, a new senior principal investigator (FTC) and project manager (FGY) were recruited, taking up post in June 2001. We summarize here the major lessons learnt in trial implementation in a resource-poor setting.","PeriodicalId":87416,"journal":{"name":"PLoS clinical trials","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1371/journal.pctr.0010016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26167999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of folic acid and betaine supplementation on flow-mediated dilation: a randomized, controlled study in healthy volunteers.","authors":"Margreet R Olthof, Michiel L Bots, Martijn B Katan, Petra Verhoef","doi":"10.1371/journal.pctr.0010010","DOIUrl":"10.1371/journal.pctr.0010010","url":null,"abstract":"<p><strong>Objectives: </strong>We investigated whether lowering of fasting homocysteine concentrations, either with folic acid or with betaine supplementation, differentially affects vascular function, a surrogate marker for risk of cardiovascular disease, in healthy volunteers. As yet, it remains uncertain whether a high concentration of homocysteine itself or whether a low folate status--its main determinant--is involved in the pathogenesis of cardiovascular disease. To shed light on this issue, we performed this study.</p><p><strong>Design: </strong>This was a randomized, placebo-controlled, double-blind, crossover study.</p><p><strong>Setting: </strong>The study was performed at Wageningen University in Wageningen, the Netherlands.</p><p><strong>Participants: </strong>Participants were 39 apparently healthy men and women, aged 50-70 y.</p><p><strong>Interventions: </strong>Participants ingested 0.8 mg/d of folic acid, 6 g/d of betaine, and placebo for 6 wk each, with 6-wk washout in between.</p><p><strong>Outcome measures: </strong>At the end of each supplementation period, plasma homocysteine concentrations and flow-mediated dilation (FMD) of the brachial artery were measured in duplicate.</p><p><strong>Results: </strong>Folic acid supplementation lowered fasting homocysteine by 20% (-2.0 micromol/l, 95% confidence interval [CI]: -2.3; -1.6), and betaine supplementation lowered fasting plasma homocysteine by 12% (-1.2 micromol/l; -1.6; -0.8) relative to placebo. Mean (+/- SD) FMD after placebo supplementation was 2.8 (+/- 1.8) FMD%. Supplementation with betaine or folic acid did not affect FMD relative to placebo; differences relative to placebo were -0.4 FMD% (95%CI, -1.2; 0.4) and -0.1 FMD% (-0.9; 0.7), respectively.</p><p><strong>Conclusions: </strong>Folic acid and betaine supplementation both did not improve vascular function in healthy volunteers, despite evident homocysteine lowering. This is in agreement with other studies in healthy participants, the majority of which also fail to find improved vascular function upon folic acid treatment. However, homocysteine or folate might of course affect cardiovascular disease risk through other mechanisms.</p>","PeriodicalId":87416,"journal":{"name":"PLoS clinical trials","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1488898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26168946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic polymorphisms and weight loss in obesity: a randomised trial of hypo-energetic high- versus low-fat diets.","authors":"Thorkild I A Sørensen,&nbsp;Philippe Boutin,&nbsp;Moira A Taylor,&nbsp;Lesli H Larsen,&nbsp;Camilla Verdich,&nbsp;Liselotte Petersen,&nbsp;Claus Holst,&nbsp;Søren M Echwald,&nbsp;Christian Dina,&nbsp;Søren Toubro,&nbsp;Martin Petersen,&nbsp;Jan Polak,&nbsp;Karine Clément,&nbsp;J Alfredo Martínez,&nbsp;Dominique Langin,&nbsp;Jean-Michel Oppert,&nbsp;Vladimir Stich,&nbsp;Ian Macdonald,&nbsp;Peter Arner,&nbsp;Wim H M Saris,&nbsp;Oluf Pedersen,&nbsp;Arne Astrup,&nbsp;Philippe Froguel","doi":"10.1371/journal.pctr.0010012","DOIUrl":"https://doi.org/10.1371/journal.pctr.0010012","url":null,"abstract":"<p><strong>Objectives: </strong>To study if genes with common single nucleotide polymorphisms (SNPs) associated with obesity-related phenotypes influence weight loss (WL) in obese individuals treated by a hypo-energetic low-fat or high-fat diet.</p><p><strong>Design: </strong>Randomised, parallel, two-arm, open-label multi-centre trial.</p><p><strong>Setting: </strong>Eight clinical centres in seven European countries.</p><p><strong>Participants: </strong>771 obese adult individuals.</p><p><strong>Interventions: </strong>10-wk dietary intervention to hypo-energetic (-600 kcal/d) diets with a targeted fat energy of 20%-25% or 40%-45%, completed in 648 participants.</p><p><strong>Outcome measures: </strong>WL during the 10 wk in relation to genotypes of 42 SNPs in 26 candidate genes, probably associated with hypothalamic regulation of appetite, efficiency of energy expenditure, regulation of adipocyte differentiation and function, lipid and glucose metabolism, or production of adipocytokines, determined in 642 participants.</p><p><strong>Results: </strong>Compared with the noncarriers of each of the SNPs, and after adjusting for gender, age, baseline weight and centre, heterozygotes showed WL differences that ranged from -0.6 to 0.8 kg, and homozygotes, from -0.7 to 3.1 kg. Genotype-dependent additional WL on low-fat diet ranged from 1.9 to -1.6 kg in heterozygotes, and from 3.8 kg to -2.1 kg in homozygotes relative to the noncarriers. Considering the multiple testing conducted, none of the associations was statistically significant.</p><p><strong>Conclusions: </strong>Polymorphisms in a panel of obesity-related candidate genes play a minor role, if any, in modulating weight changes induced by a moderate hypo-energetic low-fat or high-fat diet.</p>","PeriodicalId":87416,"journal":{"name":"PLoS clinical trials","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1371/journal.pctr.0010012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26168949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Secondary outcomes of a pilot randomized trial of azithromycin treatment for asthma.","authors":"David L Hahn, Mary Beth Plane, Olaimatu S Mahdi, Gerald I Byrne","doi":"10.1371/journal.pctr.0010011","DOIUrl":"10.1371/journal.pctr.0010011","url":null,"abstract":"<p><strong>Objectives: </strong>The respiratory pathogen Chlamydia pneumoniae (C. pneumoniae) produces acute and chronic lung infections and is associated with asthma. Evidence for effectiveness of antichlamydial antibiotics in asthma is limited. The primary objective of this pilot study was to investigate the feasibility of performing an asthma clinical trial in practice settings where most asthma is encountered and managed. The secondary objectives were to investigate (1) whether azithromycin treatment would affect any asthma outcomes and (2) whether C. pneumoniae serology would be related to outcomes. This report presents the secondary results.</p><p><strong>Design: </strong>Randomized, placebo-controlled, blinded (participants, physicians, study personnel, data analysts), allocation-concealed parallel group clinical trial.</p><p><strong>Setting: </strong>Community-based health-care settings located in four states and one Canadian province.</p><p><strong>Participants: </strong>Adults with stable, persistent asthma.</p><p><strong>Interventions: </strong>Azithromycin (six weekly doses) or identical matching placebo, plus usual community care.</p><p><strong>Outcome measures: </strong>Juniper Asthma Quality of Life Questionnaire (Juniper AQLQ), symptom, and medication changes from baseline (pretreatment) to 3 mo posttreatment (follow-up); C. pneumoniae IgG and IgA antibodies at baseline and follow-up.</p><p><strong>Results: </strong>Juniper AQLQ improved by 0.25 (95% confidence interval; -0.3, 0.8) units, overall asthma symptoms improved by 0.68 (0.1, 1.3) units, and rescue inhaler use decreased by 0.59 (-0.5, 1.6) daily administrations in azithromycin-treated compared to placebo-treated participants. Baseline IgA antibodies were positively associated with worsening overall asthma symptoms at follow-up (p = 0.04), but IgG was not (p = 0.63). Overall asthma symptom improvement attributable to azithromycin was 28% in high IgA participants versus 12% in low IgA participants (p for interaction = 0.27).</p><p><strong>Conclusions: </strong>Azithromycin did not improve Juniper AQLQ but appeared to improve overall asthma symptoms. Larger community-based trials of antichlamydial antibiotics for asthma are warranted.</p>","PeriodicalId":87416,"journal":{"name":"PLoS clinical trials","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1488900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26168947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The clinical trials directive: how is it affecting Europe's noncommercial research?","authors":"Markus Hartmann,&nbsp;Florence Hartmann-Vareilles","doi":"10.1371/journal.pctr.0010013","DOIUrl":"https://doi.org/10.1371/journal.pctr.0010013","url":null,"abstract":"In this article, we examine and discuss the current situation for noncommercial clinical trials in Europe—two years after a new legal framework entered into force. The Clinical Trials Directive, issued in 2001 [1], sought to regulate clinical research in a uniform way across Europe. The basic aims underpinning its development were to cut red tape, speed up research and development, enhance the quality of investigational drugs, harmonise procedures, increase the transparency of the clinical research process, and last, but not least, enforce patient protection. The Directive required that trialists and sponsors ensure ethical review and authorisation by competent national authorities before enrolling participants, drug manufacture in line with Good Manufacturing Practice guidelines, and rigorous observance of the Good Clinical Practice (GCP) principles during the conduct of the trial. Furthermore, the Directive required that any changes related to the execution of the clinical study, and its final results, be reported to the supervising authorities. To transpose the Directive into national law, each European Union (EU) member state has had to change its established legal framework for clinical drug research to meet the requirements of the Directive. \u0000 \u0000Since that time, the Directive has fundamentally changed the face of clinical research in Europe. While the pharmaceutical industry has become accustomed to intervening early in political decisionmaking and legislative processes, public and academic research institutions have taken more time to develop a common action plan in response to the Directive [2,3]. Perhaps due to the legal complexity of the subject, responses to the Directive's impact on noncommercial research have been limited to surveys [4,5]. Attempts to convey the current situation in the EU are restricted by language and information barriers and by insufficient resources for conducting a Europe-wide analysis.","PeriodicalId":87416,"journal":{"name":"PLoS clinical trials","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1371/journal.pctr.0010013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26168948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A randomised trial of subcutaneous intermittent interleukin-2 without antiretroviral therapy in HIV-infected patients: the UK-Vanguard Study.","authors":"Mike Youle,&nbsp;Sean Emery,&nbsp;Martin Fisher,&nbsp;Mark Nelson,&nbsp;Lisa Fosdick,&nbsp;George Janossy,&nbsp;Clive Loveday,&nbsp;Ann Sullivan,&nbsp;Christian Herzmann,&nbsp;Handan Wand,&nbsp;Richard T Davey,&nbsp;Margaret A Johnson,&nbsp;Jorge A Tavel,&nbsp;H Clifford Lane","doi":"10.1371/journal.pctr.0010003","DOIUrl":"https://doi.org/10.1371/journal.pctr.0010003","url":null,"abstract":"<p><strong>Objective: </strong>The objective of the trial was to evaluate in a pilot setting the safety and efficacy of interleukin-2 (IL-2) therapy when used without concomitant antiretroviral therapy as a treatment for HIV infection.</p><p><strong>Design and setting: </strong>This was a multicentre randomised three-arm trial conducted between September 1998 and March 2001 at three clinical centres in the United Kingdom.</p><p><strong>Participants: </strong>Participants were 36 antiretroviral treatment naïve HIV-1-infected patients with baseline CD4 T lymphocyte counts of at least 350 cells/mm(3).</p><p><strong>Interventions: </strong>Participants were randomly assigned to receive IL-2 at 15 million international units (MIU) per day (12 participants) or 9 MIU/day (12 participants) or no treatment (12 participants). IL-2 was administered by twice-daily subcutaneous injections for five consecutive days every 8 wk.</p><p><strong>Outcome measures: </strong>Primary outcome was the change from baseline CD4 T lymphocyte count at 24 wk. Safety and plasma HIV RNA levels were also monitored every 4 wk through 24 wk. The two IL-2 dose groups were combined for the primary analysis.</p><p><strong>Results: </strong>Area under curve (AUC) for change in the mean CD4 T lymphocyte count through 24 wk was 129 cells/mm(3) for those assigned IL-2 (both dose groups combined) and 13 cells/mm(3) for control participants (95% CI for difference, 51.3-181.2 cells/mm(3); p = 0.0009). Compared to the control group, significant increases in CD4 cell count were observed for both IL-2 dose groups: 104.2/mm(3) (p = 0.008) and 128.4 cells/mm(3) (p = 0.002) for the 4.5 and 7.5 MIU dose groups, respectively. There were no significant differences between the IL-2 (0.13 log(10) copies/ml) and control (0.09 log(10) copies/ml) groups for AUC of change in plasma HIV RNA over the 24-wk period of follow-up (95% CI for difference, -0.17 to 0.26; p = 0.70). Grade 4 and dose-limiting side effects were in keeping with those previously reported for IL-2 therapy.</p><p><strong>Conclusions: </strong>In participants with HIV infection and baseline CD4 T lymphocyte counts of at least 350 cells/mm(3), intermittent subcutaneous IL-2 without concomitant antiretroviral therapy was well tolerated and produced significant increases in CD4 T lymphocyte counts and did not adversely affect plasma HIV RNA levels.</p>","PeriodicalId":87416,"journal":{"name":"PLoS clinical trials","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1371/journal.pctr.0010003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26167371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}