PLoS clinical trials最新文献

{"title":"Phase III trial of albumin in malaria still lacks scientific justification.","authors":"Charles J Woodrow, Timothy Planche","doi":"10.1371/journal.pctr.0020001","DOIUrl":"https://doi.org/10.1371/journal.pctr.0020001","url":null,"abstract":"We wrote to PLoS Clinical Trials [1] following the publication of the article by Akech et al. [2] in order to highlight specific problems in the design and analysis of the study presented, point out errors in the presentation of the data, and seek clarification over certain details. As a consequence of this letter an erratum [3] to the editorial commentary has been issued confirming that no difference was found in death rate or any other outcome measure between the two arms of this study. \u0000 \u0000The authors' follow-up letter [4] reiterates claims concerning the benefit of albumin over other fluids, including Gelofusine. Unfortunately, this letter missed an opportunity to clarify a number of issues and perpetuates a number of inaccuracies. For example, the notion of albumin's superiority over Gelofusine (groundless given the lack of statistical evidence for this; see erratum) persists in the statement beginning: “The combined findings that death, severe allergic reaction, and acute neurological events were more common in the Gelofusine group…” Similarly, the erroneous total patient number included in the meta-analysis (238) is still used in preference to the correct number (239). \u0000 \u0000Phase III studies must be based on specific and relevant phase II studies. These preferably assess intervention versus standard treatment (“maintenance-only” fluids in most African hospitals) and optimise dosing strategy while rigorously and proactively noting adverse events (e.g., pulmonary oedema by chest radiography [5]). However, none of the studies on albumin performed in Kilifi have incorporated these elements into their design and reported adverse events in a standardised fashion [5]. Even the amounts of fluid actually received by patients in the most recent study are not provided [2]. Comparison of case fatality rates with historical controls cannot provide the required safety data to underpin a phase III study. Additionally, given the lack of a clear hypothesis (the authors discuss albumin acting in both volume expanding and neuroprotective capacities), the group of patients who might benefit from albumin remains uncertain. \u0000 \u0000Failure to address any of the specific points in our letter impairs the ability of readers to review primary data for themselves. Repeating arguments for phase III studies on albumin in severe malaria does not make them more compelling.","PeriodicalId":87416,"journal":{"name":"PLoS clinical trials","volume":"2 2","pages":"e1"},"PeriodicalIF":0.0,"publicationDate":"2007-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1371/journal.pctr.0020001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26612592","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":"Phase III trials required to resolve clinical equipoise over optimal fluid management in children with severe malaria.","authors":"Kathryn Maitland, Samuel Akech, Samson Gwer, Richard Idro, Greg Fegan, Alice C Eziefula, Michael Levin, Charles R J C Newton","doi":"10.1371/journal.pctr.0020002","DOIUrl":"https://doi.org/10.1371/journal.pctr.0020002","url":null,"abstract":"","PeriodicalId":87416,"journal":{"name":"PLoS clinical trials","volume":"2 2","pages":"e2"},"PeriodicalIF":0.0,"publicationDate":"2007-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1371/journal.pctr.0020002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26612591","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":"Stimulatory effect of morning bright light on reproductive hormones and ovulation: results of a controlled crossover trial.","authors":"Konstantin V Danilenko,&nbsp;Elena A Samoilova","doi":"10.1371/journal.pctr.0020007","DOIUrl":"https://doi.org/10.1371/journal.pctr.0020007","url":null,"abstract":"<p><strong>Objectives: </strong>Studies have shown a shortening of the menstrual cycle following light exposure in women with abnormally long menstrual cycles or with winter depression, suggesting that artificial light can influence reproductive hormones and ovulation. The study was designed to investigate this possibility.</p><p><strong>Design: </strong>Placebo-controlled, crossover, counterbalanced order.</p><p><strong>Setting: </strong>Medical centres and participants' homes in Novosibirsk (55 degrees N), Russia.</p><p><strong>Participants: </strong>Twenty-two women, aged 19-37 years, with baseline menstrual cycle length 28.1-37.8 d and no clinically evident endocrine abnormalities completed the study. The study lasted for two menstrual cycles separated by at least one off-protocol cycle.</p><p><strong>Interventions: </strong>During one experimental cycle, bright light was administered at home for 1 wk with a light box emitting white light at 4,300 lux at 41 cm for 45 min shortly after awakening. During the other experimental cycle, dim light was <100 lux at 41 cm with a one-tube fluorescent source.</p><p><strong>Outcome measures: </strong>Blood samples and ultrasound scans were obtained in the afternoon before and after the week of light exposure, on day approximately 7 and 14 after menstruation onset. Further ultrasound scans after day 14 documented ovulation. Serum was assayed for thyroid-stimulating hormone (TSH), prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol (E2).</p><p><strong>Results: </strong>Concentrations of PRL, LH, and FSH were significantly increased with bright versus dim light exposure, as was follicle size (ANOVA, intervention x day, p = 0.0043, 0.014, 0.049, and 0.042, respectively). The number of ovulatory cycles increased after exposure to bright compared to dim light (12 versus 6 cycles, Wilcoxon tied p = 0.034).</p><p><strong>Conclusions: </strong>Morning exposure to bright light in the follicular phase of the menstrual cycle stimulates the secretion of hypophyseal reproductive hormones, promotes ovary follicle growth, and increases ovulation rates in women with slightly lengthened menstrual cycles. This might be a promising method to overcome infertility.</p>","PeriodicalId":87416,"journal":{"name":"PLoS clinical trials","volume":"2 2","pages":"e7"},"PeriodicalIF":0.0,"publicationDate":"2007-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1371/journal.pctr.0020007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26600131","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":"Inadequate evidence to support phase III studies of albumin in severe malaria.","authors":"Charles J Woodrow,&nbsp;Timothy Planche","doi":"10.1371/journal.pctr.0020004","DOIUrl":"https://doi.org/10.1371/journal.pctr.0020004","url":null,"abstract":"There is a consensus among paediatricians that outcome of children presenting with life-threatening infections, irrespective of the infecting pathogen, can be improved by timely recognition and prompt intervention to correct disordered physiology using simple approaches to resuscitation [1–3]. These approaches include the provision of oxygen and the correction of fluid, electrolyte, and glucose deficits [4,5]. Indeed, studies have shown that most of the recent gains in survival of children with severe infections have come through the application of this approach by non-specialists during the initial hours of management [6,7]. Correction of hypotension and volume depletion through fluid administration is a fundamental component of resuscitation in most critically ill children [8,9], but its role in severe malaria remains uncertain and thus represents one of the most important theoretical gaps in our understanding of supportive treatments in this condition. \u0000 \u0000Many children with severe malaria have signs of cardiovascular compromise or compensated shock on presentation to hospital and a smaller proportion are hypotensive [10]. One of the major unresolved aspects of management is whether volume expansion should be undertaken in children displaying signs of compensated shock, as is recommended in other paediatric disorders. Intravascular volume depletion (hypovolaemic shock) results in impaired cardiovascular function and inadequate tissue and organ perfusion, and would usually be corrected rapidly. Simple dehydration, predominantly affecting the intracellular compartment, can be safely corrected gradually. The choice of the optimum fluid for resuscitation is also unclear. Colloidal solutions, although more costly, are less likely to precipitate cerebral and pulmonary oedema due to their oncotic properties. \u0000 \u0000Recognising the importance of adequate fluid management to the outcome of the critically ill child, the group at Kilifi has conducted a staged series of studies over the last 15 years to address each of these questions. In a collaboration that included specialists in paediatric intensive care, neurology, and clinical trials, the group demonstrated the importance, prognostic implications [11], and clinical correlates of metabolic acidosis in children with severe malaria [12] and provided clear evidence of intravascular hypovolaemia by using standard methods for studying critical illness [13]. We have undertaken two randomised trials to assess the safety of and response to volume expansion, and to determine whether colloid replacement offers any advantage over crystalloid replacement [13,14]. We hypothesised that administration of colloids such as human albumin solution with volume expansion would help to retain fluid in the intravascular compartment and may also improve endothelial function. In each of these trials we observed that albumin administration was associated with a lower mortality than saline. Although this data suggested the need for","PeriodicalId":87416,"journal":{"name":"PLoS clinical trials","volume":"2 2","pages":"e4"},"PeriodicalIF":0.0,"publicationDate":"2007-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1371/journal.pctr.0020004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26600130","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":"Correction: Evolution and Translation of Research Findings: From Bench to Where?","authors":"J. Ioannidis","doi":"10.1371/journal.pctr.0020003","DOIUrl":"https://doi.org/10.1371/journal.pctr.0020003","url":null,"abstract":"In PLoS Clinical Trials, vol 1, issue 7: doi:10.1371/journal.pctr.0010036 \u0000 \u0000In Box 2, Reference [52] should be corrected to [22]. References [18-21] in the text should be corrected to [18-22]. The six successive references from [22] to [27] in the text should be corrected to [23] to [28]. Finally, the current reference [28] in the text should be corrected to [14].","PeriodicalId":87416,"journal":{"name":"PLoS clinical trials","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2007-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66664551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunotherapy with canarypox vaccine and interleukin-2 for HIV-1 infection: termination of a randomized trial.","authors":"Kendall A Smith, Sofija Andjelic, Zoran Popmihajlov, Liza Kelly-Rossini, Aquanette Sass, Martin Lesser, Steven Benkert, Cory Waters, Joyce Ruitenberg, Paul Bellman","doi":"10.1371/journal.pctr.0020005","DOIUrl":"10.1371/journal.pctr.0020005","url":null,"abstract":"<p><strong>Objectives: </strong>To determine whether immunotherapy of chronic HIV-1 infection can prevent or attenuate viremia upon antiviral discontinuation.</p><p><strong>Design: </strong>This was a Phase II randomized, partially double blinded, 2x2 factorial study of three steps of 12 wk/step. Step I involved four groups: (1) vaccine placebo, (2) vaccine (ALVAC, vCP1452), (3) placebo + interleukin 2 (IL-2), and (4) vaccine + IL-2. Step II involved a 12-wk diagnostic treatment interruption (DTI). Step III involved an extension of the DTI for an additional 12 wk.</p><p><strong>Setting: </strong>The Weill-Cornell General Clinical Research Center.</p><p><strong>Participants: </strong>Chronically infected HIV-1 positive adults with undetectable HIV-1 levels and > 400 CD4+ T cells/microl.</p><p><strong>Interventions: </strong>An HIV canarypox vaccine (vCP1452) and vaccine placebo, administered every 4 wk for four doses, and low-dose IL-2 administered daily for 12-24 wk.</p><p><strong>Outcome measures: </strong>Primary endpoints: (1) Proportion of participants with undetectable plasma HIV RNA during trial Step II, (2) mean log10 HIV RNA copies/ml ([HIV]) from weeks 21-25, and (3) proportion of individuals eligible for trial Step III.</p><p><strong>Results: </strong>44 participants were randomized, but 16 withdrew or were withdrawn before completing Step II. As all participants underwent viral relapse in Step II, the study was terminated after 28 participants completed Step II. Among the four groups, there was no difference in mean [HIV] or the proportion of individuals with < log10 4.48 HIV; no difference between the mean [HIV] of the two groups that received ALVAC (n = 17) versus placebo (n = 11); and no significant difference between the mean [HIV] of the two groups that received IL-2 (n = 11) versus placebo (n = 17).</p><p><strong>Conclusions: </strong>Neither ALVAC (vCP1452) nor low-dose daily IL-2 nor their combination prevented the relapse of viremia upon discontinuation of antiviral therapy.</p>","PeriodicalId":87416,"journal":{"name":"PLoS clinical trials","volume":"2 1","pages":"e5"},"PeriodicalIF":0.0,"publicationDate":"2007-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1783674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26574009","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":"Randomized dose-ranging controlled trial of AQ-13, a candidate antimalarial, and chloroquine in healthy volunteers.","authors":"Fawaz Mzayek, Haiyan Deng, Frances J Mather, Elizabeth C Wasilevich, Huayin Liu, Christiane M Hadi, David H Chansolme, Holly A Murphy, Bekir H Melek, Alan N Tenaglia, David M Mushatt, Albert W Dreisbach, Juan J L Lertora, Donald J Krogstad","doi":"10.1371/journal.pctr.0020006","DOIUrl":"10.1371/journal.pctr.0020006","url":null,"abstract":"<p><strong>Objectives: </strong>To determine: (1) the pharmacokinetics and safety of an investigational aminoquinoline active against multidrug-resistant malaria parasites (AQ-13), including its effects on the QT interval, and (2) whether it has pharmacokinetic and safety profiles similar to chloroquine (CQ) in humans.</p><p><strong>Design: </strong>Phase I double-blind, randomized controlled trials to compare AQ-13 and CQ in healthy volunteers. Randomizations were performed at each step after completion of the previous dose.</p><p><strong>Setting: </strong>Tulane-Louisiana State University-Charity Hospital General Clinical Research Center in New Orleans.</p><p><strong>Participants: </strong>126 healthy adults 21-45 years of age.</p><p><strong>Interventions: </strong>10, 100, 300, 600, and 1,500 mg oral doses of CQ base in comparison with equivalent doses of AQ-13.</p><p><strong>Outcome measures: </strong>Clinical and laboratory adverse events (AEs), pharmacokinetic parameters, and QT prolongation.</p><p><strong>Results: </strong>No hematologic, hepatic, renal, or other organ toxicity was observed with AQ-13 or CQ at any dose tested. Headache, lightheadedness/dizziness, and gastrointestinal (GI) tract-related symptoms were the most common AEs. Although symptoms were more frequent with AQ-13, the numbers of volunteers who experienced symptoms with AQ-13 and CQ were similar (for AQ-13 and CQ, respectively: headache, 17/63 and 10/63, p = 0.2; lightheadedness/dizziness, 11/63 and 8/63, p = 0.6; GI symptoms, 14/63 and 13/63; p = 0.9). Both AQ-13 and CQ exhibited linear pharmacokinetics. However, AQ-13 was cleared more rapidly than CQ (respectively, median oral clearance 14.0-14.7 l/h versus 9.5-11.3 l/h; p < or = 0.03). QTc prolongation was greater with CQ than AQ-13 (CQ: mean increase of 28 ms; 95% confidence interval [CI], 18 to 38 ms, versus AQ-13: mean increase of 10 ms; 95% CI, 2 to 17 ms; p = 0.01). There were no arrhythmias or other cardiac AEs with either AQ-13 or CQ.</p><p><strong>Conclusions: </strong>These studies revealed minimal differences in toxicity between AQ-13 and CQ, and similar linear pharmacokinetics.</p>","PeriodicalId":87416,"journal":{"name":"PLoS clinical trials","volume":"2 1","pages":"e6"},"PeriodicalIF":0.0,"publicationDate":"2007-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1764434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26481942","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":"Phase 1 study of two merozoite surface protein 1 (MSP1(42)) vaccines for Plasmodium falciparum malaria.","authors":"Elissa Malkin,&nbsp;Carole A Long,&nbsp;Anthony W Stowers,&nbsp;Lanling Zou,&nbsp;Sanjay Singh,&nbsp;Nicholas J MacDonald,&nbsp;David L Narum,&nbsp;Aaron P Miles,&nbsp;Andrew C Orcutt,&nbsp;Olga Muratova,&nbsp;Samuel E Moretz,&nbsp;Hong Zhou,&nbsp;Ababacar Diouf,&nbsp;Michael Fay,&nbsp;Eveline Tierney,&nbsp;Philip Leese,&nbsp;Siddhartha Mahanty,&nbsp;Louis H Miller,&nbsp;Allan Saul,&nbsp;Laura B Martin","doi":"10.1371/journal.pctr.0020012","DOIUrl":"https://doi.org/10.1371/journal.pctr.0020012","url":null,"abstract":"<p><strong>Objectives: </strong>To assess the safety and immunogenicity of two vaccines, MSP1(42)-FVO/Alhydrogel and MSP1(42)-3D7/Alhydrogel, targeting blood-stage Plasmodium falciparum parasites.</p><p><strong>Design: </strong>A Phase 1 open-label, dose-escalating study.</p><p><strong>Setting: </strong>Quintiles Phase 1 Services, Lenexa, Kansas between July 2004 and November 2005.</p><p><strong>Participants: </strong>Sixty healthy malaria-naïve volunteers 18-48 y of age.</p><p><strong>Interventions: </strong>The C-terminal 42-kDa region of merozoite surface protein 1 (MSP1(42)) corresponding to the two allelic forms present in FVO and 3D7 P. falciparum lines were expressed in Escherichia coli, refolded, purified, and formulated on Alhydrogel (aluminum hydroxide). For each vaccine, volunteers in each of three dose cohorts (5, 20, and 80 microg) were vaccinated at 0, 28, and 180 d. Volunteers were followed for 1 y.</p><p><strong>Outcome measures: </strong>The safety of MSP1(42)-FVO/Alhydrogel and MSP1(42)-3D7/Alhydrogel was assessed. The antibody response to each vaccine was measured by reactivity to homologous and heterologous MSP1(42), MSP1(19), and MSP1(33) recombinant proteins and recognition of FVO and 3D7 parasites.</p><p><strong>Results: </strong>Anti-MSP1(42) antibodies were detected by ELISA in 20/27 (74%) and 22/27 (81%) volunteers receiving three vaccinations of MSP1(42)-FVO/Alhydrogel or MSP1(42)-3D7/Alhydrogel, respectively. Regardless of the vaccine, the antibodies were cross-reactive to both MSP1(42)-FVO and MSP1(42)-3D7 proteins. The majority of the antibody response targeted the C-terminal 19-kDa domain of MSP1(42), although low-level antibodies to the N-terminal 33-kDa domain of MSP1(42) were also detected. Immunofluorescence microscopy of sera from the volunteers demonstrated reactivity with both FVO and 3D7 P. falciparum schizonts and free merozoites. Minimal in vitro growth inhibition of FVO or 3D7 parasites by purified IgG from the sera of the vaccinees was observed.</p><p><strong>Conclusions: </strong>The MSP1(42)/Alhydrogel vaccines were safe and well tolerated but not sufficiently immunogenic to generate a biologic effect in vitro. Addition of immunostimulants to the Alhydrogel formulation to elicit higher vaccine-induced responses in humans may be required for an effective vaccine.</p>","PeriodicalId":87416,"journal":{"name":"PLoS clinical trials","volume":"2 4","pages":"e12"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1371/journal.pctr.0020012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26649646","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":"Rifampicin/Cotrimoxazole/Isoniazid versus mefloquine or quinine + sulfadoxine- pyrimethamine for malaria: a randomized trial.","authors":"Blaise Genton,&nbsp;Ivo Mueller,&nbsp;Inoni Betuela,&nbsp;Gerard Casey,&nbsp;Meza Ginny,&nbsp;Michael P Alpers,&nbsp;John C Reeder","doi":"10.1371/journal.pctr.0010038","DOIUrl":"https://doi.org/10.1371/journal.pctr.0010038","url":null,"abstract":"<p><strong>Objectives: </strong>Previous studies of a fixed combination including cotrimoxazole, rifampicin, and isoniazid (Cotrifazid) showed efficacy against resistant strains of Plasmodium falciparum in animal models and in small-scale human studies. We conducted a multicentric noninferiority trial to assess the safety and efficacy of Cotrifazid against drug-resistant malaria in Papua New Guinea.</p><p><strong>Design: </strong>The trial design was open-label, block-randomised, comparative, and multicentric.</p><p><strong>Setting: </strong>The trial was conducted in four primary care health facilities, two in urban and two in rural areas of Madang and East Sepik Province, Papua New Guinea.</p><p><strong>Participants: </strong>Patients of all ages with recurrent uncomplicated malaria were included.</p><p><strong>Interventions: </strong>Patients were randomly assigned to receive Cotrifazid, mefloquine, or the standard treatment of quinine with sulfadoxine-pyrimethamine (SP).</p><p><strong>Outcome measures: </strong>Incidence of clinical and laboratory adverse events and rate of clinical and/or parasitological failure at day 14 were recorded.</p><p><strong>Results: </strong>The safety analysis population included 123 patients assigned to Cotrifazid, 123 to mefloquine, and 123 to quinine + SP. The Cotrifazid group experienced lower overall incidence of adverse events than the other groups. Among the efficacy analysis population (72 Cotrifazid, 71 mefloquine, and 75 quinine + SP), clinical failure rate (symptoms and parasite load) on day 14 was equivalent for the three groups (0% for Cotrifazid and mefloquine; 1% for quinine + SP), but parasitological failure rate (P. falciparum asexual blood-stage) was higher for Cotrifazid than for mefloquine or quinine + SP (9% [PCR corrected 8%] versus 0% and 3%, respectively [p = 0.02]).</p><p><strong>Conclusion: </strong>Despite what appears to be short-term clinical equivalence, the notable parasitological failure at day 14 in both P. falciparum and P. vivax makes Cotrifazid in its current formulation and regimen a poor alternative combination therapy for malaria.</p>","PeriodicalId":87416,"journal":{"name":"PLoS clinical trials","volume":"1 8","pages":"e38"},"PeriodicalIF":0.0,"publicationDate":"2006-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1371/journal.pctr.0010038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26463982","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 suspension of treatments in ADAPT: concerns beyond the cardiovascular safety of celecoxib or naproxen.","authors":"John C S Breitner,&nbsp;Barbara K Martin,&nbsp;Curtis L Meinert","doi":"10.1371/journal.pctr.0010041","DOIUrl":"https://doi.org/10.1371/journal.pctr.0010041","url":null,"abstract":"","PeriodicalId":87416,"journal":{"name":"PLoS clinical trials","volume":"1 8","pages":"e41"},"PeriodicalIF":0.0,"publicationDate":"2006-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1371/journal.pctr.0010041","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26463983","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}