scholarly journals A Prospective, Open-label, Randomized Trial of Doxycycline Versus Azithromycin for the Treatment of Uncomplicated Murine Typhus

2018 ◽  
Vol 68 (5) ◽  
pp. 738-747 ◽  
Author(s):  
Paul N Newton ◽  
Valy Keolouangkhot ◽  
Sue J Lee ◽  
Khamla Choumlivong ◽  
Siho Sisouphone ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Randomized Trial ◽  
Randomized Clinical Trials ◽  
Similar Efficacy ◽  
Clearance Time ◽  
Murine Typhus ◽  
Open Label ◽  
Clinical Trial Registration ◽  
Fever Clearance Time ◽  
Polymerase Chain

Abstract Background Murine typhus, or infection with Rickettsia typhi, is a global but neglected disease without randomized clinical trials to guide antibiotic therapy. Methods A prospective, open, randomized trial was conducted in nonpregnant, consenting inpatient adults with rapid diagnostic test evidence of uncomplicated murine typhus at 2 hospitals in Vientiane, Laos. Patients were randomized to 7 days (D7) or 3 days (D3) of oral doxycycline or 3 days of oral azithromycin (A3). Primary outcome measures were fever clearance time and frequencies of treatment failure and relapse. Results Between 2004 and 2009, the study enrolled 216 patients (72 per arm); 158 (73.2%) had serology/polymerase chain reaction (PCR)–confirmed murine typhus, and 52 (24.1%) were R. typhi PCR positive. The risk of treatment failure was greater for regimen A3 (22.5%; 16 of 71 patients) than for D3 (4.2%; 3 of 71) or D7 (1.4%; 1 of 71) (P < .001). Among R. typhi PCR–positive patients, the area under the time-temperature curve and the fever clearance time were significantly higher for A3 than for D3 (1.8- and 1.9-fold higher, respectively; P = .005) and D7 (1.5- and 1.6-fold higher; P = .02). No patients returned with PCR-confirmed R. typhi relapse. Conclusion In Lao adults, azithromycin is inferior to doxycycline as oral therapy for uncomplicated murine typhus. For doxycycline, 3- and 7-day regimens have similar efficacy. Azithromycin use in murine typhus should be reconsidered. Investigation of genomic and phenotypic markers of R. typhi azithromycin resistance is needed. Clinical Trial Registration ISRCTN47812566.

scholarly journals Administration of the vasopressin analog desmopressin for the management of bleeding in rectal cancer patients: results of a phase I/II trial

2020 ◽  
Vol 38 (5) ◽  
pp. 1580-1587
Author(s):  
Soledad Iseas ◽  
Enrique L. Roca ◽  
Juan M. O’Connor ◽  
Martin Eleta ◽  
Analia Sanchez-Luceros ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Cancer Patients ◽  
Randomized Clinical Trials ◽  
Complete Response ◽  
Maximum Tolerated Dose ◽  
Dose Finding ◽  
Metastatic Progression ◽  
Tumor Perfusion ◽  
Open Label ◽  
Clinical Trial Registration

Summary Purpose The vasopressin analog desmopressin (dDAVP) is known to increase plasma levels of hemostatic factors, and preclinical studies in colorectal cancer models have demonstrated that it hampers tumor vascularization and metastatic progression. We evaluated safety and preliminary efficacy of dDAVP in rectal cancer patients with bleeding, before receiving specific oncologic treatment with surgery, chemotherapy and/or radiotherapy. Methods Patients with rectal cancer having moderate or severe rectal bleeding were enrolled in an open-label, dose-finding trial. Intravenous infusions of dDAVP were administered during two consecutive days in doses from 0.25 to 2.0 µg/kg, using single or twice daily regimen. Bleeding was graded using a score based on the Chutkan scale and tumor perfusion was evaluated by dynamic contrast-enhanced magnetic resonance imaging. Results The trial accrued a total of 32 patients. Dose-limiting toxicity occurred in patients receiving 1 µg/kg or higher. The most prominent treatment-related severe adverse event was hyponatremia. Most patients receiving the maximum tolerated dose of 0.5 µg/kg showed at least a partial hemostatic response and 58% developed a complete response with absence of bleeding at day 4 and/or at the last follow-up at day 14. Tumor perfusion was decreased in two-thirds of patients after dDAVP treatment. Conclusions dDAVP appeared as a promising hemostatic agent in rectal cancer patients with bleeding. Randomized clinical trials to confirm its effectiveness are warranted. Clinical trial registrationwww.clinicaltrials.gov NCT01623206

scholarly journals Clinical Response and Outcome of Infection with Salmonella enterica Serotype Typhi with Decreased Susceptibility to Fluoroquinolones: a United States FoodNet Multicenter Retrospective Cohort Study

2008 ◽  
Vol 52 (4) ◽  
pp. 1278-1284 ◽  
Author(s):  
John A. Crump ◽  
Katrina Kretsinger ◽  
Kathryn Gay ◽  
R. Michael Hoekstra ◽  
Duc J. Vugia ◽  
...  
Keyword(s):  
Cohort Study ◽  
Treatment Failure ◽  
Nalidixic Acid ◽  
Retrospective Cohort Study ◽  
Salmonella Enterica ◽  
Retrospective Cohort ◽  
Clearance Time ◽  
Fever Clearance Time ◽  
Show Evidence ◽  
Experienced Treatment

ABSTRACT Patients with typhoid fever due to Salmonella enterica serotype Typhi strains for which fluoroquinolones MICs are elevated yet that are classified as susceptible by the current interpretive criteria of the Clinical and Laboratory Standards Institute may not respond adequately to fluoroquinolone therapy. Patients from seven U.S. states with invasive Salmonella serotype Typhi infection between 1999 and 2002 were enrolled in a multicenter retrospective cohort study. Patients infected with Salmonella serotype Typhi isolates with ciprofloxacin MICs of 0.12 to 1 μg/ml (decreased ciprofloxacin susceptibility but not resistant to ciprofloxacin [DCS]) were compared with patients infected with isolates with ciprofloxacin MICs <0.12 μg/ml for fever clearance time and treatment failure. Of 71 patients, 30 (43%) were female and 24 (34%) were infected with Salmonella serotype Typhi with DCS; the median age was 14 years (range, 1 to 51 years). Twenty-one (88%) of 24 isolates with DCS were resistant to nalidixic acid. The median antimicrobial-related fever clearance times in the DCS and non-DCS groups were 92 h (range, 21 to 373 h) and 72 h (range, 19 to 264 h) (P = 0.010), respectively, and the fluoroquinolone-related fever clearance times in the DCS and non-DCS groups were 90 h (range, 9 to 373 h) and 64 h (range, 34 to 204 h) (P = 0.153), respectively. Four (17%) of 24 patients in the DCS group and 2 (4%) of 46 patients in the non-DCS group (relative risk, 2.5; 95% confidence interval, 1.2 to 5.1) experienced treatment failure. Associations persisted after adjustment for potential confounders. We demonstrate that patients infected with Salmonella serotype Typhi isolates with DCS show evidence of a longer time to fever clearance and more frequent treatment failure. Nalidixic acid screening does not detect all isolates with DCS.

scholarly journals Trimethoprim-sulfamethoxazole Versus Azithromycin for the Treatment of Undifferentiated Febrile Illness in Nepal: A Double-blind, Randomized, Placebo-controlled Trial

2020 ◽  
Author(s):  
Abhishek Giri ◽  
Abhilasha Karkey ◽  
Sabina Dangol ◽  
Amit Arjyal ◽  
Sunil Pokharel ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Enteric Fever ◽  
Controlled Trial ◽  
Febrile Illness ◽  
Blood Cultures ◽  
Clearance Time ◽  
Double Blind ◽  
Fever Clearance Time ◽  
Secondary Endpoints ◽  
Fever Treatment

Abstract Background Azithromycin and trimethoprim-sulfamethoxazole (SXT) are widely used to treat undifferentiated febrile illness (UFI). We hypothesized that azithromycin is superior to SXT for UFI treatment, but the drugs are noninferior to each other for culture-confirmed enteric fever treatment. Methods We conducted a double-blind, randomized, placebo-controlled trial of azithromycin (20 mg/kg/day) or SXT (trimethoprim 10 mg/kg/day plus sulfamethoxazole 50 mg/kg/day) orally for 7 days for UFI treatment in Nepal. We enrolled patients &gt;2 years and &lt;65 years of age presenting to 2 Kathmandu hospitals with temperature ≥38.0°C for ≥4 days without localizing signs. The primary endpoint was fever clearance time (FCT); secondary endpoints were treatment failure and adverse events. Results From June 2016 to May 2019, we randomized 326 participants (163 in each arm); 87 (26.7%) had blood culture–confirmed enteric fever. In all participants, the median FCT was 2.7 days (95% confidence interval [CI], 2.6–3.3 days) in the SXT arm and 2.1 days (95% CI, 1.6–3.2 days) in the azithromycin arm (hazard ratio [HR], 1.25 [95% CI, .99–1.58]; P = .059). The HR of treatment failures by 28 days between azithromycin and SXT was 0.62 (95% CI, .37–1.05; P = .073). Planned subgroup analysis showed that azithromycin resulted in faster FCT in those with sterile blood cultures and fewer relapses in culture-confirmed enteric fever. Nausea, vomiting, constipation, and headache were more common in the SXT arm. Conclusions Despite similar FCT and treatment failure in the 2 arms, significantly fewer complications and relapses make azithromycin a better choice for empirical treatment of UFI in Nepal. Clinical Trials Registration NCT02773407.

scholarly journals Enteroadsorbent Polymethylsiloxane Polyhydrate vs. Probiotic Lactobacillus reuteri DSM 17938 in the Treatment of Rotaviral Gastroenteritis in Infants and Toddlers, a Randomized Controlled Trial

2020 ◽  
Vol 8 ◽  
Author(s):  
Leo Markovinović ◽  
Ivica Knezović ◽  
Tihana Kniewald ◽  
Lorna Stemberger Marić ◽  
Vladimir Trkulja ◽  
...  
Keyword(s):  
Lactobacillus Reuteri ◽  
Controlled Trial ◽  
Similar Efficacy ◽  
University Hospital ◽  
Bowel Habit ◽  
Open Label ◽  
Clinical Trial Registration ◽  
Recommended Treatment ◽  
Significant Difference ◽  
The University

Purpose: The aim of this study was to compare two adjunct therapies in the treatment of childhood rotavirus gastroenteritis (RVGE). We compared the recommended treatment, probiotic Lactobacillus reuteri DSM 17938 (BioGaia®), vs. a novel treatment, enterosorbent polymethylsiloxane polyhydrate (Enterosgel®).Methods: This was an open-label, randomized, clinical controlled trial at the University Hospital for Infectious Diseases (UHID) in Zagreb, Croatia. A total of 149 children aged 6–36 months with acute rotaviral gastroenteritis over a period of &lt;48 h, with no significant chronic comorbidity, were randomized to receive the standard therapy with L. reuteri DSM 17938 (hereafter L. reuteri) or polymethylsiloxane polyhydrate (hereafter PMSPH) therapy, during 5 days. The primary end point was time to recovery in days in both groups. The recovery was defined as absence of fever and vomiting and either the first firm stool, absence of stool for more than 24 h, or return of usual bowel habit.Results: A total of 75 children were randomized into the L. reuteri group and 74 were randomized into the PMSPH group; after excluding missing data, the data from 65 children in each group were analyzed. There was no significant difference in the treatment efficacy between the two regimens with an estimated median time of recovery of 6 days in both groups (p = 0.754). No significant side effects were observed in either group.Conclusion: Novel enterosorbent PMSPH had a similar efficacy to probiotic L. reuteri in the treatment of rotaviral gastroenteritis in preschool children.Clinical Trial Registration:ClinicalTrials.gov Identifier: NCT04116307 [October 3, 2019] (retrospectively registered). https://clinicaltrials.gov/show/NCT04116307.

scholarly journals Mefloquine versus Quinine plus Sulphalene-Pyrimethamine (Metakelfin) for Treatment of Uncomplicated Imported Falciparum Malaria Acquired in Africa

2005 ◽  
Vol 49 (2) ◽  
pp. 663-667 ◽  
Author(s):  
Alberto Matteelli ◽  
Nuccia Saleri ◽  
Zeno Bisoffi ◽  
Giampietro Gregis ◽  
Giovanni Gaiera ◽  
...  
Keyword(s):  
Hospital Stay ◽  
Length Of Hospital Stay ◽  
Parasite Clearance ◽  
Clearance Time ◽  
Cure Rate ◽  
African Countries ◽  
Open Label ◽  
Fever Clearance Time ◽  
To Receive

ABSTRACT We conducted a multicenter, randomized, open-label trial to compare mefloquine with a 3-day quinine plus sulphalene-pyrimethamine (SP) regimen for the treatment of imported uncomplicated malaria acquired in Africa. The end points of the study were efficacy, tolerability, and length of hospital stay. From July 1999 to February 2003, 187 patients were enrolled in five centers in Italy, of whom 93 were randomized to receive mefloquine (the M group) and 94 were randomized to receive quinine plus SP (the QSP group). Immigrants and visiting relatives and friends represented 90% of the cases and were mainly from western African countries. A slightly increased proportion of cases in the QSP group had abnormal alanine aminotransferase levels at the baseline. The early cure rate was similar in the two groups: 98.9% (confidence interval [CI] = 97 to 100%) in the M group and 96.8% (CI = 93 to 100%) in the QSP group. The extended follow-up was completed by 135 subjects (72.2%), and no case of recrudescence was detected. There were no differences in the parasite clearance time, but patients in the M group had shorter mean fever clearance time (35.9 h versus 44.4 h for the QSP group; P = 0.05) and a shorter mean hospital stay (3.9 days versus 4.6 days for the QSP group; P = 0.007). The overall proportions of reported side effects were similar in the two groups, but patients in the M group had a significantly higher rate of central nervous system disturbances (29.0% versus 9.6% for the QSP group; P < 0.001).

scholarly journals Efficacy of artemether-lumefantrine and artesunate-amodiaquine for treating uncomplicated falciparum malaria in children

2012 ◽  
Vol 52 (5) ◽  
pp. 260
Author(s):  
Tri Faranita ◽  
Ayodhia Pitaloka Pasaribu ◽  
Muhammad Ali ◽  
Munar Lubis ◽  
Syahril Pasaribu
Keyword(s):  
Treatment Failure ◽  
Falciparum Malaria ◽  
Controlled Trial ◽  
Parasite Clearance ◽  
Uncomplicated Falciparum Malaria ◽  
Clearance Time ◽  
Parasite Clearance Time ◽  
Fever Clearance Time ◽  
Late Treatment ◽  
Cure Rates

Background Artesunate-amodiaquine (ASAQ) has been usedas a firsdine treatment for uncomplicated faldparum malariain Indonesia since 2004. Its efficacy depends on amodiaquineresistance of the infecting parasites. Artemether-lumefantrine(AL) has been shown to be highly efficacious in treatinguncomplicated faldparum malaria in several countries. However,there have been few studies on these anti-malarial medicationsin Indonesia.Objective To compare the efficacy of AL to ASAQ for treatinguncomplicated faldparum malaria in children.Methods An open, randomized, controlled trial wasconducted in school-aged children in the Mandailing NatalRegency, North Sumatera Province, Indonesia, from Octoberto December 2010. A total of 280 pediatric, uncomplicatedfalciparum malaria patients were randomly assigned to receiveeither AL or ASAQ for 3 days. Participants were followed-up ondays 1,2,3,7, 14, 28 and 42 following the first medication dose.The outcomes noted were adequate clinical and parasitologicalresponse (ACPR), parasite reduction, parasite clearance time,fever clearance time and adverse events. Analysis was basedon intention-to-treat.Results In this study, ACPRs on day 42 were 86.4% and 90.7%for the ASAQ and AL groups, respectively (p=0.260). On days 7and 14, the AL group had higher cure rates than that of the ASAQgroup (P<0.05). Early treatment failure, late treatment failure andparasitological failure for both groups were similar. We also foundfaster parasite clearance time and higher parasite reduction in theAL group than in the ASAQ group. However, fever clearancetime was shorter in the ASAQ group. The incidence of adverseevents such as nausea, vomiting, malaise, and pruritus were similarbetween the two groups (P=0.441).Conclusion AL had higher efficacy than ASAQ for the treatment of uncomplicated falciparum malaria in children.[Paediatr rndones. 2012;52:260-6].

Long- versus short-term androgen deprivation therapy with high-dose radiotherapy for biochemical failure after radical prostatectomy: a randomized controlled trial

2020 ◽  
Vol 16 (27) ◽  
pp. 2035-2044
Author(s):  
Charlien Berghen ◽  
Steven Joniau ◽  
Annouschka Laenen ◽  
Gaetan Devos ◽  
Kato Rans ◽  
...  
Keyword(s):  
Radical Prostatectomy ◽  
Androgen Deprivation Therapy ◽  
Controlled Trial ◽  
Locally Advanced ◽  
Lymph Node Involvement ◽  
Androgen Deprivation ◽  
High Dose ◽  
Open Label ◽  
Clinical Trial Registration ◽  
Substantial Risk

Radical prostatectomy is a well-established treatment option in the management of localized and locally advanced prostate cancer. An extended lymphadenectomy is performed in case of substantial risk for lymph node involvement. When biochemical recurrence (BCR) occurs, salvage radiotherapy (SRT) is performed. The benefit in terms of BCR-free survival (FS) and metastasis-FS by adding 6 months of androgen deprivation therapy (ADT) compared with SRT only has already been established. Retrospective evidence suggests that a longer schedule of ADT may be more beneficial compared with 6 months. This multicenter open-label randomized trial will include patients who need SRT after experiencing BCR post-radical prostatectomy with lymphadenectomy and pN0-status. Patients will be randomized for ADT duration (6 vs 24 months). Primary end point is distant metastasis-FS. Clinical Trial Registration: NCT04242017 ( ClinicalTrials.gov )

scholarly journals Adherence to Ketogenic and Mediterranean Study Diets in a Crossover Trial: The Keto–Med Randomized Trial

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 967
Author(s):  
Matthew J. Landry ◽  
Anthony Crimarco ◽  
Dalia Perelman ◽  
Lindsay R. Durand ◽  
Christina Petlura ◽  
...  
Keyword(s):  
Randomized Trial ◽  
Randomized Clinical Trials ◽  
Secondary Analysis ◽  
Critical Factor ◽  
Detailed Examination ◽  
Diet Patterns ◽  
Time Points ◽  
Study Results ◽  
Wide Range ◽  
Diet Pattern

Adherence is a critical factor to consider when interpreting study results from randomized clinical trials (RCTs) comparing one diet to another, but it is frequently not reported by researchers. The purpose of this secondary analysis of the Keto–Med randomized trial was to provide a detailed examination and comparison of the adherence to the two study diets (Well Formulated Ketogenic Diet (WFKD) and Mediterranean Plus (Med-Plus)) under the two conditions: all food being provided (delivered) and all food being obtained by individual participants (self-provided). Diet was assessed at six time points including baseline (x1), week 4 of each phase when participants were receiving food deliveries (x2), week 12 of each phase when participants were preparing and providing food on their own (x2), and 12 weeks after participants completed both diet phases and were free to choose their own diet pattern (x1). The adherence scores for WFKD and Med-Plus were developed specifically for this study. Average adherence to the two diet patterns was very similar during both on-study time points of the intervention. Throughout the study, a wide range of adherence was observed among participants—for both diet types and during both the delivery phase and self-provided phase. Insight from this assessment of adherence may aid other researchers when answering the important question of how to improve behavioral adherence during dietary trials. This study is registered at clinicaltrials.gov NCT03810378.

scholarly journals Phase I first-in-human study of HLX07, a novel and improved recombinant anti-EGFR humanized monoclonal antibody, in patients with advanced solid cancers

2021 ◽  
Author(s):  
Ming-Mo Hou ◽  
Ching-Liang Ho ◽  
Hsuan-Yu Lin ◽  
Yunting Zhu ◽  
Xiaodi Zhang
Keyword(s):  
Phase I ◽  
Standard Therapy ◽  
Human Study ◽  
Growth Factor Receptor ◽  
Systemic Exposure ◽  
Open Label ◽  
Dose Escalation Study ◽  
Clinical Trial Registration ◽  
Humanized Monoclonal Antibody ◽  
Open Label Phase

SummaryPurpose This study aimed to evaluate the safety and pharmacokinetic (PK) profiles of HLX07, a novel, recombinant, humanized anti-epidermal growth factor receptor (EGFR) antibody, in patients with advanced solid cancers who had failed standard therapy or for whom no standard therapy was available. Methods In this prospective, open-label, Phase I dose escalation study, patients aged ≥18 years (≥20 years for patients in Taiwan) with histologically-confirmed metastatic or recurrent epithelial carcinoma that had no K-RAS or B-RAF mutations were enrolled in a ‘3 + 3’ escalation design. HLX07 was administered weekly by 2-h intravenous infusion at doses ranging from 50 to 800 mg. The primary endpoint was summary listing of participants reporting treatment-emergent adverse events (TEAEs). Secondary endpoints included PK analysis, serum anti-HLX07 antibody assessments and efficacy. Results In total, 19 patients were enrolled between 1 October 2016 and 16 July 2019 to receive HLX07 at doses of 50 (n = 3), 100 (n = 3), 200 (n = 3), 400 (n = 3), 600 (n = 3) and 800 (n = 4) mg per week. All patients experienced at least one TEAE, most commonly fatigue (68.4%), nausea (47.4%), paronychia (31.6%) and vomiting (31.6%). Serious TEAEs were reported in 11 patients but only one serious TEAE (dyspnea in 600 mg cohort) was regarded as possibly related to study treatment. No dose limiting toxicity (DLT) was reported. Systemic exposure to HLX07 increased proportionally with dose. Anti-HLX07 antibodies were not detected in any patients. Conclusion HLX07 was well tolerated (at dose levels up to 800 mg/week) and promising in patients with advanced solid cancers.Clinical Trial Registration: The study was registered at ClinicalTrials.gov: NCT02648490 (Jan 7, 2016).

Sign in / Sign up

Export Citation Format

Share Document