scholarly journals An open label study of the safety and efficacy of a single dose of weekly chloroquine and azithromycin administered for malaria prophylaxis in healthy adults challenged with 7G8 chloroquine-resistant Plasmodium falciparum in a controlled human malaria infection model

2020 ◽  
Author(s):  
Jeffrey Livezey ◽  
Patrick Twomey ◽  
Meshell Morrison ◽  
Susan Cicatelli ◽  
Elizabeth H Duncan ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
High Rate ◽  
Control Group ◽  
Infection Model ◽  
Post Challenge ◽  
Open Label ◽  
Open Label Study ◽  
Label Study ◽  
Malaria Chemoprophylaxis ◽  
To Receive

Abstract BackgroundMalaria remains the top infectious disease threat facing the U.S. military in many forward operating environments. Compliance with malaria chemoprophylaxis remains a critical component in preventing malaria in the deployed Service Member. Studies of previous military operations show that compliance is consistently higher with weekly versus daily dosing regimens. Current FDA approved weekly chemoprophylaxis options have contraindications that can limit prescribing. The combination of chloroquine (CQ) with azithromycin (AZ) has previously been shown to be an efficacious treatment option for malaria, has pharmacokinetics compatible with weekly dosing, and has shown synergy when combined in vitro. MethodsIn this open label study 18 healthy volunteers, aged 18-50 years (inclusive), were randomly assigned to receive either 300 mg CQ or 300 mg CQ and 2 gm azithromycin (CQAZ) of directly observed therapy, weekly for 3 weeks prior to undergoing mosquito bite challenge with chloroquine-resistant Plasmodium falciparum. Volunteers that remained asymptomatic and had no evidence of parasitaemia continued to receive weekly post-exposure chemoprophylaxis for 3 weeks following malaria challenge. The primary endpoint was the number of volunteers that remained asymptomatic and had no evidence of parasitaemia 28 days after the malaria challenge.ResultsAll 6 (100%) volunteers randomized to the CQ control group became symptomatic with parasitaemia during the 28-day post-challenge period. Only 1/12 (8.3%) of volunteers in the CQAZ group developed symptoms and parasitaemia during the 28-day post-challenge period. However, after chemoprophylaxis was discontinued an additional 6 volunteers developed parasitaemia between days 28-41 after challenge, with 4 of 6 experiencing symptoms. 80% of subjects in the CQAZ group experienced treatment related gastrointestinal adverse events (including 13 % that experienced severe nausea) compared to 38% in the CQ group. A comparison of the pharmacokinetics in the CQAZ group demonstrated higher azithromycin Cmax (p0.03) and AUC (p0.044) levels in those volunteers who never became parasitaemic compared to those who did. ConclusionGiven the high rate of side effects and poor efficacy when administered for 3 weeks before and after challenge, the combination of weekly chloroquine and azithromycin is a suboptimal regimen combination for weekly malaria chemoprophylaxis.Trial registration: ClinicalTrials.gov NCT03278808

scholarly journals An open label study of the safety and efficacy of a single dose of weekly chloroquine and azithromycin administered for malaria prophylaxis in healthy adults challenged with 7G8 chloroquine-resistant Plasmodium falciparum in a controlled human malaria infection model

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Jeffrey Livezey ◽  
Patrick Twomey ◽  
Meshell Morrison ◽  
Susan Cicatelli ◽  
Elizabeth H. Duncan ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
High Rate ◽  
Control Group ◽  
Infection Model ◽  
Post Challenge ◽  
Open Label ◽  
Open Label Study ◽  
Label Study ◽  
Malaria Chemoprophylaxis ◽  
To Receive

Abstract Background Malaria remains the top infectious disease threat facing the U.S. military in many forward operating environments. Compliance with malaria chemoprophylaxis remains a critical component in preventing malaria in the deployed Service Member. Studies of previous military operations show that compliance is consistently higher with weekly versus daily dosing regimens. Current FDA approved weekly chemoprophylaxis options have contraindications that can limit prescribing. The combination of chloroquine (CQ) with azithromycin (AZ) has previously been shown to be an efficacious treatment option for malaria, has pharmacokinetics compatible with weekly dosing, and has shown synergy when combined in vitro. Methods In this open label study, 18 healthy volunteers, aged 18–50 years (inclusive), were randomly assigned to receive either 300 mg CQ or 300 mg CQ and 2 gm azithromycin (CQAZ) of directly observed therapy, weekly for 3 weeks prior to undergoing mosquito bite challenge with chloroquine-resistant Plasmodium falciparum. Volunteers that remained asymptomatic and had no evidence of parasitaemia continued to receive weekly post-exposure chemoprophylaxis for 3 weeks following malaria challenge. The primary endpoint was the number of volunteers that remained asymptomatic and had no evidence of parasitaemia 28 days after the malaria challenge. Results All 6 (100%) volunteers randomized to the CQ control group became symptomatic with parasitaemia during the 28-day post-challenge period. Only 1/12 (8.3%) of volunteers in the CQAZ group developed symptoms and parasitaemia during the 28-day post-challenge period. However, after chemoprophylaxis was discontinued an additional 6 volunteers developed parasitaemia between days 28–41 after challenge, with 4 of 6 experiencing symptoms. 80% of subjects in the CQAZ group experienced treatment related gastrointestinal adverse events (including 13% that experienced severe nausea) compared to 38% in the CQ group. A comparison of the pharmacokinetics in the CQAZ group demonstrated higher azithromycin Cmax (p = 0.03) and AUC (p = 0.044) levels in those volunteers who never became parasitaemic compared to those who did. Conclusion Given the high rate of side effects and poor efficacy when administered for 3 weeks before and after challenge, the combination of weekly chloroquine and azithromycin is a suboptimal regimen combination for weekly malaria chemoprophylaxis. Trial registration ClinicalTrials.gov NCT03278808

scholarly journals An Open Label Study of the Safety and Efficacy of a Single Dose of Weekly Chloroquine and Azithromycin Administered for Malaria Prophylaxis in Healthy Adults Challenged with 7G8 Chloroquine-Resistant Plasmodium falciparum in a Controlled Human Malaria Infection (CHMI) Model

2020 ◽  
Author(s):  
Jeffrey Livezey ◽  
Patrick Twomey ◽  
Meshell Morrison ◽  
Susan Cicatelli ◽  
Elizabeth H Duncan ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
High Rate ◽  
Control Group ◽  
Directly Observed Therapy ◽  
Post Challenge ◽  
Open Label ◽  
Severe Nausea ◽  
Open Label Study ◽  
Label Study ◽  
To Receive

Abstract Background: Malaria remains the top infectious disease threat facing the U.S. military in many forward operating environments. Compliance with malaria chemoprophylaxis remains a critical component in preventing malaria in the deployed Service Member. Studies of previous military operations show that compliance is consistently higher with weekly versus daily dosing regimens. Current FDA approved weekly chemoprophylaxis options have contraindications that can limit prescribing. The combination of chloroquine (CQ) with azithromycin (AZ) has previously been shown to be an efficacious treatment option for malaria, has pharmacokinetics compatible with weekly dosing, and has shown synergy when combined in vitro. Methods: In this open label study 18 healthy volunteers, aged 18-50 years (inclusive), were randomly assigned to receive either 300 mg CQ or 300 mg CQ and 2 gm azithromycin (CQAZ) of directly observed therapy, weekly for 3 weeks prior to undergoing mosquito bite challenge with chloroquine-resistant Plasmodium falciparum. Volunteers that remained asymptomatic and had no evidence of parasitemia continued to receive weekly post-exposure chemoprophylaxis for 3 weeks following malaria challenge. The primary endpoint was the number of volunteers that remained asymptomatic and had no evidence of parasitemia 28 days after the malaria challenge.Results: All 6 (100%) volunteers randomized to the CQ control group became symptomatic with parasitemia during the 28 day post-challenge period. Only 1/12 (8.3%) of volunteers in the CQAZ group developed symptoms and parasitemia during the 28-day post-challenge period. However, after chemoprophylaxis was discontinued an additional 6 volunteers developed parasitemia between days 28-41 after challenge, with 4 of 6 experiencing symptoms. 80% of subjects in the CQAZ group experienced treatment related gastrointestinal adverse events (including 13 % that experienced severe nausea) compared to 38% in the CQ group. A comparison of the pharmacokinetics in the CQAZ group demonstrated higher azithromycin Cmax (p0.03) and AUC (p0.044) levels in those volunteers who never became parasitemic compared to those who did. Conclusion: Given the high rate of side effects and poor efficacy when administered for 3 weeks before and after challenge, the combination of weekly chloroquine and azithromycin is a suboptimal regimen combination for weekly malaria chemoprophylaxis.Trial registration: ClinicalTrials.gov NCT03278808

scholarly journals An Open Label Study of the Safety and Efficacy of a Single Dose of Weekly Chloroquine and Azithromycin Administered for Malaria Prophylaxis in Healthy Adults Challenged with 7G8 Chloroquine-Resistant Plasmodium falciparum in a Controlled Human Malaria Infection (CHMI) Model

2020 ◽  
Author(s):  
Jeffrey Livezey ◽  
Patrick Twomey ◽  
Meshell Morrison ◽  
Susan Cicatelli ◽  
Elizabeth H Duncan ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Infection ◽  
Post Challenge ◽  
Open Label ◽  
Open Label Study ◽  
Label Study ◽  
Human Malaria ◽  
Malaria Chemoprophylaxis ◽  
Controlled Human Malaria Infection ◽  
To Receive

Abstract Background: Malaria remains the top infectious disease threat facing the U.S. military in many forward operating environments. Compliance with malaria chemoprophylaxis remains a critical component in preventing malaria in the deployed Service Member. Studies of previous military operations show that compliance is consistently higher with weekly versus daily dosing regimens. Current FDA approved weekly chemoprophylaxis options have contraindications that can limit prescribing. The combination of chloroquine (CQ) with azithromycin (AZ) has previously been shown to be an efficacious treatment option for malaria, has pharmacokinetics compatible with weekly dosing, and has shown synergy when combined in vitro.Methods: In this open label study 18 healthy volunteers, aged 18-50 years (inclusive), were randomly assigned to receive either 300 mg CQ or 300 mg CQ and 2 gm azithromycin (CQAZ) of directly observed therapy, weekly for 3 weeks prior to undergoing mosquito bite challenge with chloroquine-resistant Plasmodium falciparum. Volunteers that remained asymptomatic and had no evidence of parasitemia continued to receive weekly post-exposure chemoprophylaxis for 3 weeks following malaria challenge. The primary endpoint was the number of volunteers that remained asymptomatic and had no evidence of parasitemia 28 days after the malaria challenge.Results: All 6 (100%) volunteers randomized to the CQ control group became symptomatic with parasitemia during the 28 day post-challenge period. Only 1/12 (8.3%) of volunteers in the CQAZ group developed symptoms and parasitemia during the 28-day post-challenge period. However, after chemoprophylaxis was discontinued an additional 6 volunteers developed parasitemia between days 28-41 after challenge, with 4 of 6 experiencing symptoms. 80% of subjects in the CQAZ group experienced treatment related gastrointestinal adverse events (including 13 % that experienced severe nausea) compared to 38% in the CQ group. A comparison of the pharmacokinetics in the CQAZ group demonstrated higher azithromycin Cmax (p0.03) and AUC (p0.044) levels in those volunteers who never became parasitemic compared to those who did.Conclusion: Given the high rate of side effects and poor efficacy when administered for 3 weeks before and after challenge, the combination of weekly chloroquine and azithromycin is a suboptimal regimen combination for weekly malaria chemoprophylaxis.Trial registration: ClinicalTrials.gov NCT03278808 Key words: malaria chemoprophylaxis, azithromycin, chloroquine, controlled human malaria infection

Sustained clinical benefits of glatiramer acetate in relapsing multiple sclerosis patients observed for 6 years

2000 ◽  
Vol 6 (4) ◽  
pp. 255-266 ◽  
Author(s):  
K P Johnson ◽  
B R Brooks ◽  
C C Ford ◽  
A Goodman ◽  
J Guarnaccia ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Glatiramer Acetate ◽  
Relapse Rate ◽  
Open Label ◽  
Double Blind ◽  
Open Label Study ◽  
Label Study ◽  
Open Label Phase ◽  
Multiple Sclerosis Patients ◽  
To Receive

In a randomized, placebo-controlled, double-blind study, glatiramer acetate (Copaxone®) reduced the relapse rate and slowed accumulation of disability for patients with relapsing-remitting multiple sclerosis. Of the original 251 patients randomized to receive glatiramer acetate or placebo, 208 chose to continue in an open-label study with all patients receiving active drug. The majority of the original double-blind cohort continues to receive glatiramer acetate by daily subcutaneous injection and are evaluated at 6-month intervals and during suspected relapse. The data reported here are from approximately 6 years of organized evaluation, including the double-blind phase of up to 35 months and the open-label phase of over 36 months. Daily subcutaneous injections of 20 mg glatiramer acetate were well tolerated. The mean annual relapse rate of the patients who received glatiramer acetate since randomization and continued into the open-label study was 0.42 (95% confidence interval (CI), CI=0.34-0.51). The rate per year has continued to drop and for the sixth year is 0.23. Of the group who have received glatiramer acetate without interruption for 5 or more years, 69.3% were neurologically unchanged or have improved from baseline by at least one step on the Expanded Disability Status Scale (EDSS). Patients who left the open-label phase were surveyed by questionnaire. The majority responded, providing information about their current status and reasons for dropping out. This study demonstrates the sustained efficacy of glatiramer acetate in reducing the relapse rate and in slowing the accumulation of disability in patients with relapsing forms of multiple sclerosis.

Rate of complete chemotherapy as planned with comprehensive geriatric assessment guided intervention among vulnerable elderly cancer patients: A randomized-open-label study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e24021-e24021
Author(s):  
Manupol Maikami ◽  
Napa Parinyanitikul ◽  
Nattaya Poovorawan
Keyword(s):  
Usual Care ◽  
Cancer Patients ◽  
Comprehensive Geriatric Assessment ◽  
Intervention Group ◽  
Control Group ◽  
Open Label ◽  
Elderly Cancer Patients ◽  
Open Label Study ◽  
Label Study ◽  
Significant Difference

e24021 Background: The Geriatric 8 (G8) is a simplified screening tool to select the appropriate elderly patients for chemotherapy. Vulnerable patients with impaired G8 score might need additional comprehensive geriatric assessment (CGA) with intervention for individual problem. However, the impact of CGA and therapeutic intervention on rate of complete chemotherapy among these patients is rarely addressed. This study aims to evaluate the benefit of CGA guided intervention. Methods: A single center, randomized, open-label study which included newly diagnosed elderly cancer patients (age ≥ 65) with impaired G8 score (≤ 14) who were designated for chemotherapy. After the enrollment, patients were randomized to 1:1 ratio to receive CGA guided intervention (intervention group) or usual care (control group). The primary end point was the rate of complete chemotherapy at 90-day. Associated factors for complete chemotherapy were evaluated. Results: Between June 2019 and December 2019, 52 patients were randomized (26 patients for intervention group and 26 patients for control group). Mean age was 72 years, 59.6% was female, 40.4% had breast cancer and 51.9% had early stage cancer. With G8 assessment, 55.8% had intermediate (score 11-14) and 44.2% had low (score < 11) impaired G8 score. All baseline characteristics were balanced. Using per protocol analysis, there was no significant difference in rate of complete chemotherapy between groups (61.9% vs 50%, OR 1.63; 95%Cl 0.51-5.23; p = 0.42). Considering subgroup analysis in the intermediate G8 score patients, the intervention group had a significant higher rate of complete chemotherapy than control group (81.8% vs 66.7%, OR 2.71; p = 0.02), but no significant difference in low G8 score group (40% vs 27.3%, OR 1.78; p = 0.58). In univariate analysis, age below 75 years, BMI > 20 kg/m2 and intermediate G8 score showed significant factors for improving rate of complete chemotherapy. Conclusions: This is the first study in south-east Asia using CGA and intervention to improve rate of completion in chemotherapy. Although the CGA and intervention had no significant difference but had tendency to be better in completion rate of chemotherapy than usual care. The intermediate-impaired G8 score subgroup is more likely to benefit from CGA guided intervention for complete chemotherapy as planned.

Effect of personalized wrist orthosis for wrist pain with three-dimensional scanning and printing technique: A preliminary, randomized, controlled, open-label study

2018 ◽  
Vol 42 (6) ◽  
pp. 636-643 ◽  
Author(s):  
Sang Jun Kim ◽  
Sung Jae Kim ◽  
Yong Ho Cha ◽  
Keun Ho Lee ◽  
Jeong-Yi Kwon
Keyword(s):  
Hand Function ◽  
Three Dimensional ◽  
Wrist Pain ◽  
Control Group ◽  
Open Label ◽  
Open Label Study ◽  
Label Study ◽  
High Satisfaction ◽  
Significant Difference ◽  
Experimental Group

Background: Three-dimensional printer technology can produce the personalized orthosis in various forms. Objective: To develop a personalized wrist orthosis using a three-dimensional scanner and three-dimensional printer for patients with wrist pain. Study design: A preliminary, prospective, randomized, open-label study. Methods: A total of 22 patients with wrist pain were randomly assigned to the control and experimental groups. The control group wore a cock-up orthosis and the experimental group wore a three-dimensional-printed wrist orthosis for 1 week. The Patient-Rated Wrist Evaluation, Jebsen Hand Function Test, and Orthotics and Prosthetics Users’ Survey were checked before and 1 week after the application. Results: The Patient-Rated Wrist Evaluation showed significant pain relief in both groups. Two items of the 28 Orthotics and Prosthetics Users’ Survey questions, “Put toothpaste on brush and brush teeth” and “Dial a touch tone phone,” showed high satisfaction scores, with statistically significant difference in the experimental group ( p = 0.036 and 0.004). Conclusion: The three-dimensional-printed wrist orthosis was superior to the cock-up orthosis for two items of the Orthotics and Prosthetics Users’ Survey. Wrist pain was reduced in the group wearing the three-dimensional-printed wrist orthosis as well as the group wearing the cock-up orthosis, so the three-dimensional-printed wrist orthosis could possibly play the same role as the cock-up orthosis. Clinical relevance A three-dimensional-printed wrist orthosis can be a substitute for a conventional ready-made wrist orthosis for patients with wrist pain with more satisfaction.

scholarly journals Igg Food Antibody Guided Elimination-Rotation Diet Was More Effective than FODMAP Diet and Control Diet in the Treatment of Women with Mixed IBS—Results from an Open Label Study

2021 ◽  
Vol 10 (19) ◽  
pp. 4317
Author(s):  
Lucyna Ostrowska ◽  
Diana Wasiluk ◽  
Camille F. J. Lieners ◽  
Mirosława Gałęcka ◽  
Anna Bartnicka ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Abdominal Pain ◽  
Control Diet ◽  
Dietary Treatment ◽  
Control Group ◽  
Open Label ◽  
Open Label Study ◽  
Label Study ◽  
Irritable Bowel ◽  
Fodmap Diet

Irritable bowel syndrome (IBS) is a chronic disease with recurrent abdominal pain, disturbed bowel emptying, and changes in stool consistency. We compared the effectiveness of three different dietary treatment plans (G1-FM-low FODMAP diet, G2-IP IgG based elimination-rotation-diet, and as control group, the G3-K control diet recommended by an attending gastroenterologist) in treating patients diagnosed with mixed irritable bowel syndrome. A total of seventy-three female patients diagnosed with a mixed form of irritable bowel syndrome (IBS-M) were enrolled in the study. The diet of each patient in Group 1 (G1-FM) and 2 (G2-IP) was determined individually during a meeting with a dietitian. Patients from Group 3 (G3-K) received nutrition advice from a gastroenterologist. Significant differences in the reduction of IBS symptoms were found between the groups. IBS symptoms as well as comorbid symptoms significantly improved or disappeared completely in the G2-IP group (idiopathic abdominal pain, p < 0.001; abdominal pain after a meal, p < 0.001; abdominal pain during defecation, p = 0.008), while in the G1-FM group, some of the IBS symptoms significantly improved (mucus in stool, p = 0.031; bloating, p < 0.001). In group G3-K no significant improvement was seen. Based on the results of this open-label study, it was concluded that various dietary interventions in the treatment of IBS-M patients do not uniformly affect the course and outcomes of disease management. Rotation diets based on IgG show significantly better results compared to other diets.

scholarly journals Phase II, Randomized, Open-Label Study of Pegfilgrastim-Supported VDC/IE Chemotherapy in Pediatric Sarcoma Patients

2010 ◽  
Vol 28 (8) ◽  
pp. 1329-1336 ◽  
Author(s):  
Sheri L. Spunt ◽  
Helen Irving ◽  
Jami Frost ◽  
Leonard Sender ◽  
Matthew Guo ◽  
...  
Keyword(s):  
Pediatric Patients ◽  
Age Groups ◽  
Efficacy And Safety ◽  
Older Children ◽  
Open Label ◽  
Myelosuppressive Chemotherapy ◽  
Open Label Study ◽  
Label Study ◽  
Pediatric Sarcoma ◽  
To Receive

Purpose This multicenter, randomized, open-label study evaluated the efficacy, safety, and pharmacokinetics of a single subcutaneous pegfilgrastim injection with daily subcutaneous filgrastim administration in pediatric patients receiving myelosuppressive chemotherapy for sarcoma. Patients and Methods Forty-four patients with previously untreated, biopsy-proven sarcoma stratified into three age groups (0-5, 6-11, and 12-21 years) were randomly assigned in a 6:1 randomization ratio to receive a single pegfilgrastim dose of 100 μg/kg (n = 38) or daily filgrastim doses of 5 μg/kg (n = 6) after chemotherapy (cycles 1 and 3: vincristine-doxorubicin-cyclophosphamide; cycles 2 and 4: ifosfamide-etoposide). The duration of grade 4 neutropenia, time to neutrophil recovery, incidence of febrile neutropenia, and adverse events were recorded. Results Pegfilgrastim and filgrastim were similar for all efficacy and safety end points, and their pharmacokinetic profiles were consistent with those in adults. Younger children experienced more protracted neutropenia and had higher median pegfilgrastim exposure than older children. Conclusion A single dose of pegfilgrastim at 100 μg/kg administered once per chemotherapy cycle is comparable to daily injections of filgrastim at 5 μg/kg for pediatric sarcoma patients receiving myelosuppressive chemotherapy.

scholarly journals Prospective Trial of a Novel Nomogram to Achieve Updated Vancomycin Trough Concentrations

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Amber R. Wesner ◽  
Marcia L. Brackbill ◽  
Larissa L. Coyle ◽  
Robert S. Kidd
Keyword(s):  
Prospective Trial ◽  
Active Group ◽  
Control Group ◽  
New Order ◽  
Open Label ◽  
Open Label Study ◽  
Label Study ◽  
Dosing Regimens ◽  
Vancomycin Trough ◽  
Trough Concentrations

Purpose. To determine if the use of a novel vancomycin nomogram predicts dosing regimens that achieve target trough concentrations equal to or more accurate than dosing regimens calculated using traditional pharmacokinetic calculations, evaluate the incidence of subtherapeutic and supratherapeutic troughs, and assess pharmacist's impressions of the nomogram.Methods. Prospective, open-label study in 473 patients who had a new order for vancomycin and were >18 years of age and ≤120 kg. Patients were randomized to the active group, dosed using the nomogram, or to the control group, dosed using traditional pharmacokinetic calculations already in place at our institution.Results. Patients dosed via nomogram were within the appropriate trough range in 44% of cases compared to 33% in the control group (P=0.014). Vancomycin troughs less than 10 mcg/mL were significantly decreased with the use of nomogram (P=0.032). Incidence of supratherapeutic troughs, greater than 20 mcg/mL, was not significantly different between groups (P=0.706), and pharmacists agreed that the nomogram was easy to use and saved their time.Conclusions. A novel vancomycin nomogram was prospectively validated and found to be more effective than traditional pharmacokinetic dosing. The nomogram is being implemented as the standard dosing protocol at our institution.

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