Gallium Nitrate

1992 ◽  
Vol 26 (3) ◽  
pp. 354-362 ◽  
Author(s):  
Thomas E. Hughes ◽  
Lea Ann Hansen
Keyword(s):  
Clinical Trials ◽  
English Language ◽  
Therapeutic Potential ◽  
Data Extraction ◽  
Phase Iii ◽  
Gallium Nitrate ◽  
Therapeutic Effects ◽  
Two Phase ◽  
Trial Quality ◽  
Comparative Trials

OBJECTIVE: To evaluate the therapeutic role of gallium nitrate in the treatment of hypercalcemia associated with malignancy and related disease states. DATA SOURCES: A literature search of English-language studies involving gallium nitrate for the period 1966–1991 using MEDLINE and the bibliographies of relevant articles. STUDY SELECTION: Because of the limited number of studies, all clinical trials were reviewed, with particular emphasis on Phase III comparative trials. Related investigative studies on the pharmacology, pharmacokinetics, and toxicity of gallium nitrate were also reviewed. DATA EXTRACTION: Two appraisers independently abstracted data from available clinical trials and evaluated trial quality. RESULTS OF DATA SYNTHESIS: Two Phase III comparative trials evaluating gallium nitrate in the treatment of hypercalcemia of malignancy have been completed. Gallium nitrate was shown to be superior to both calcitonin and etidronate disodium, based on the comparative percentage of patients achieving normocalcemia and the subsequent duration of normocalcemia. Both trials employed similar methodology. Positive therapeutic effects of gallium nitrate have also been demonstrated in small, noncomparative trials for hypercalcemia associated with parathyroid carcinoma, Paget's disease of bone, and osteolytic bone metastases. CONCLUSIONS: Gallium nitrate is effective in the treatment of hypercalcemia associated with malignancy and is appropriate for formulary addition. In certain clinical situations, it may be clearly advantageous over such agents as calcitonin, plicamycin, and etidronate. Further investigation is needed to define the limitations of nephrotoxicity and the therapeutic potential for other indications. Further comparative clinical trials of gallium nitrate versus bisphosphonates and plicamycin could also help define its relative clinical benefit.

Bezlotoxumab: Could This be the Answer for Clostridium difficile Recurrence?

2017 ◽  
Vol 51 (9) ◽  
pp. 804-810 ◽  
Author(s):  
Ryan W. Chapin ◽  
Tiffany Lee ◽  
Christopher McCoy ◽  
Carolyn D. Alonso ◽  
Monica V. Mahoney
Keyword(s):  
Monoclonal Antibody ◽  
Clostridium Difficile ◽  
English Language ◽  
Adverse Drug Events ◽  
Data Extraction ◽  
Standard Of Care ◽  
Phase Iii ◽  
Relative Reduction ◽  
Two Phase ◽  
Mesh Terms

Objective: To review the pharmacology, pharmacokinetics, efficacy, safety, and place in therapy of bezlotoxumab (BEZ), a novel monoclonal antibody against Clostridium difficile toxin B. Data Sources: A PubMed search was conducted for data between 1946 and April 2017 using MeSH terms bezlotoxumab, MK-6072, or MDX-1388 alone and the terms Clostridium difficile combined with monoclonal antibody or antitoxin. Study Selection and Data Extraction: The literature search was limited to English-language studies that described clinical efficacy, safety, and pharmacokinetics in humans and animals. Abstracts featuring prepublished data were also evaluated for inclusion. Data Synthesis: BEZ is indicated for adult patients receiving standard-of-care (SoC) antibiotics for C difficile infection (CDI) to prevent future recurrence. Two phase III trials—MODIFY I (n = 1452) and MODIFY II (n = 1203)—demonstrated a 40% relative reduction in recurrent CDI (rCDI) with BEZ compared with placebo (16.5% vs 26.6%, P < 0.0001). The most common adverse drug events associated with BEZ were mild to moderate infusion-related reactions (10.3%). Conclusions: In patients treated with SoC antibiotics, BEZ is effective in decreasing rCDI. BEZ has no apparent effect on treatment of an initial CDI episode. In light of increasing rates of CDI, BEZ is a promising option for preventing recurrent episodes. The greatest benefit has been demonstrated in high-risk patients, though the targeted patient population is yet to be defined.

scholarly journals Amifampridine for the Management of Lambert-Eaton Myasthenic Syndrome: A New Take on an Old Drug

2019 ◽  
Vol 54 (1) ◽  
pp. 56-63
Author(s):  
Connie H. Yoon ◽  
Jocelyn Owusu-Guha ◽  
Adam Smith ◽  
Pamela Buschur
Keyword(s):  
English Language ◽  
Human Subjects ◽  
Data Extraction ◽  
Phase Iii ◽  
Pharmacokinetic Studies ◽  
First Line ◽  
Two Phase ◽  
Phase Iii Trials ◽  
Improved Stability ◽  
Myasthenic Syndrome

Objective: The purpose of this article is to review the literature for both 3,4-diaminopyridine (3,4-DAP) and amifampridine for the treatment of Lambert-Eaton myasthenic syndrome (LEMS). Amifampridine (Firdapse) is the salt form of 3,4-DAP and was approved by the Food and Drug Administration for the treatment of LEMS. Data Sources: PubMed, TRIP database, and EMBASE searches were conducted without a back date (current to June 2019) utilizing the following search terms: amifampridine, 3,4-diaminopyridine, and Lambert-Eaton myasthenic syndrome. Completed trials were also reviewed at clinicaltrials.gov. Study Selection and Data Extraction: Criteria for article inclusion consisted of human subjects, age ≥18 years, phase II or III clinical trials, and English language for both drugs. Observational and pharmacokinetic studies for amifampridine were also included. Data Synthesis: Prior to the approval of amifampridine, 3,4-DAP was first-line for the management of LEMS symptoms. Two phase III trials have evaluated amifampridine to confirm efficacy, both showing superiority over placebo in the management of LEMS symptoms, with minimal adverse effects. A significant improvement in both quantitative myasthenia gravis scores and Subjective Global Impression scores was established at days 4 and 14. Relevance to Patient Care and Clinical Practice: With an improved stability profile and decreased dose variability, amifampridine will likely assume the role of first-line management of LEMS. Conclusions: Amifampridine has been shown to improve symptoms of LEMS and is generally well tolerated.

Ocrelizumab: A New B-cell Therapy for Relapsing Remitting and Primary Progressive Multiple Sclerosis

2017 ◽  
Vol 52 (5) ◽  
pp. 473-483 ◽  
Author(s):  
Amanda M. Stahnke ◽  
Kathryn M. Holt
Keyword(s):  
Multiple Sclerosis ◽  
B Cell ◽  
English Language ◽  
Data Extraction ◽  
Progressive Multiple Sclerosis ◽  
Phase Iii ◽  
Primary Progressive Multiple Sclerosis ◽  
Two Phase ◽  
Primary Progressive ◽  
Relapsing Remitting

Objective: To review the pharmacology, pharmacokinetics, efficacy, and safety of ocrelizumab, a new B-cell–targeted therapy for multiple sclerosis (MS). Data Sources: A comprehensive search of PubMed and OVID/MEDLINE was conducted using search terms ocrelizumab and multiple sclerosis using the date range of 1946 through October 2017. Study Selection and Data Extraction: All English-language, human-subject articles related to ocrelizumab and MS were evaluated. Data Synthesis: Ocrelizumab was approved in March 2017 for the treatment of relapsing or primary progressive MS (PPMS). A phase II trial established 600 mg intravenously every 6 months as the preferred dosing schedule. Two phase III trials evaluated the efficacy of ocrelizumab in patients with relapsing remitting MS, and individual and pooled analysis demonstrated a significant reduction in annualized relapse rate ( P < 0.001 pooled), disability progression at 12 weeks ( P < 0.001 pooled), and gadolinium-enhancing lesions on magnetic resonance imaging (MRI; P < 0.001). Patients with PPMS were evaluated in a third phase III trial, which showed a significant decrease in disease progression at 12 weeks ( P = 0.03) and volume of T2-weighted lesions on MRI ( P < 0.001). As with other monoclonal antibodies, adverse effects seen with ocrelizumab were primarily infusion-related reactions and infection. Conclusions: Ocrelizumab demonstrated efficacy in the treatment of relapsing and PPMS and is the first therapy approved for patients with PPMS.

scholarly journals Andexanet alfa for reversal of factor Xa inhibitor-associated anticoagulation

2019 ◽  
Vol 10 ◽  
pp. 204209861988813 ◽  
Author(s):  
Elise Carpenter ◽  
Divita Singh ◽  
Eric Dietrich ◽  
John Gums
Keyword(s):  
Clinical Trials ◽  
English Language ◽  
Factor Xa ◽  
Signs And Symptoms ◽  
Phase Iii ◽  
Close Monitoring ◽  
Two Phase ◽  
Fxa Inhibitor ◽  
Andexanet Alfa ◽  
Ischemic Events

Background: Review of clinical data on andexanet alfa for the reversal of factor Xa (FXa) inhibitor associated anticoagulation. Data sources: In the present review, we identified articles via PubMed using the combined keywords andexanet alfa, apixaban, enoxaparin, edoxaban, and rivaroxaban. Additional online searches via PubMed, Google Scholar, and Lexicomp were conducted for both prescribing and cost information. Portola Pharmaceuticals was contacted for information used for United States Food and Drug Administration approval of andexanet alfa. Study selection and data extraction: English-language clinical trials and reviews published between January 2008 and April 2019 were included for review. Bibliographies of selected articles were reviewed manually for relevant publications, focusing on reversal strategies for apixaban, enoxaparin, edoxaban, or rivaroxaban associated anticoagulation using andexanet alfa. Review articles were excluded. Data synthesis: The safety and tolerability of andexanet alfa were evaluated in one phase I, two phase II, and one phase III clinical trials. The use of andexanet alfa for reversing FXa inhibitor-associated anticoagulation were evaluated in the phase III ANNEXA-4 study. Conclusions: Studies evaluating laboratory parameters for coagulation show that andexanet alfa rapidly neutralizes the anticoagulant effects of apixaban, enoxaparin, edoxaban, and rivaroxaban. Clinical studies show that andexanet alfa improves markers related to coagulation, and reverses major bleeding in healthy volunteers and patients with life-threatening bleeding. Interruption of anticoagulation may result in thromboembolic and ischemic events. The use of andexanet alfa requires close monitoring for signs and symptoms of thromboembolic events, ischemic events, and cardiac arrest. Furthermore, anticoagulation should be resumed following the administration of andexanet alfa as soon as medically appropriate.

Trifarotene for the Treatment of Facial and Truncal Acne

2020 ◽  
Vol 55 (1) ◽  
pp. 111-116
Author(s):  
Katheryn A. Bell ◽  
Caitlin M. Brumfiel ◽  
Wasim Haidari ◽  
Laura Boger
Keyword(s):  
Clinical Trials ◽  
Global Assessment ◽  
English Language ◽  
Data Extraction ◽  
Acne Vulgaris ◽  
Treatment Success ◽  
Phase Iii ◽  
Fourth Generation ◽  
Success Rates ◽  
Topical Retinoid

Objective: This article reviews clinical trials to assess the efficacy, safety, and clinical application of trifarotene 0.005% cream (Aklief). Data Sources: A systematic review of the literature was performed using the terms trifarotene OR Aklief OR CD5789 in MEDLINE (PubMed) and EMBASE databases. Articles prior to May 2020 were considered for inclusion. Bibliographies and ClinicalTrials.gov were also searched to identify further studies. Study Selection and Data Extraction: Relevant English language and human studies related to pharmacology, clinical trials, and safety were considered. Data Synthesis: In the 52-week phase III trial, treatment success rates for facial acne (Investigator Global Assessment [IGA] rating of no or almost no acne) and truncal acne (Physician’s Global Assessment [PGA] rating of no or almost no acne) were 65.1% and 66.9%, respectively. Overall success rates (IGA and PGA success in the same patient) were 57.9%; 52.8% of patients had a Dermatology Quality of Life Index score of 0 or 1, compared with 22.6% at baseline. Trifarotene was well tolerated, with pruritus, irritation, and sunburn as the most common adverse effects. Relevance to Patient Care and Clinical Practice: Trifarotene is a newly Food and Drug Administration–labeled fourth-generation topical retinoid that shows particular promise in the treatment of facial and truncal acne vulgaris. It is an effective and safe addition to currently available retinoids. Conclusion: Trifarotene is effective and safe for treatment of facial and truncal acne. Future trials should compare its efficacy and tolerability with that of the older, clinically established retinoids. Despite efficacy, cost may be a prohibitive factor.

Acute Management of Cancer-Related Hypercalcemia

1996 ◽  
Vol 30 (5) ◽  
pp. 507-513 ◽  
Author(s):  
Marie A Chisholm ◽  
Anthony L Mulloy ◽  
A Thomas Taylor
Keyword(s):  
Clinical Trials ◽  
English Language ◽  
Data Extraction ◽  
Symptomatic Relief ◽  
Gallium Nitrate ◽  
Medline Search ◽  
Patients With Cancer ◽  
Study Selection ◽  
Life Threatening ◽  
Acute Hypercalcemia

OBJECTIVE: TO review the pathogenesis and pharmacologic treatment of acute hypercalcemia associated with malignancy. DATA SOURCES: A MEDLINE search (1966 to 1995) of the English-language literature pertaining to acute hypercalcemia was performed. Additional literature was obtained from reference lists of articles identified through the search. STUDY SELECTION AND DATA EXTRACTION: All articles discussing the etiology and medical management of cancer-related acute hypercalcemia were considered in the review. Clinical trials reporting efficacy and safety of antihypercalcemic agents were also included. Information selected in the review was based on the discretion of the authors. DATA SYNTHESIS: Hypercalcemia is a life-threatening disorder associated with malignancy. It occurs in approximately 10–20% of patients with cancer. A variety of medications have been used in the management of hypercalcemia including bisphosphonates, calcitonin, furosemide, gallium nitrate, glucocorticoids, NaCl 0.9%, and plicamycin. Each of these agents has been reviewed with consideration of pharmacologic mechanism of action, evaluation of clinical trials, recommended dosages, efficacy, safety, cost, and role in treating cancer-related acute hypercalcemia. CONCLUSIONS: Immediate management of cancer-related acute hypercalcemia to prevent death and provide symptomatic relief is warranted. Severity determined by symptoms, calcium concentrations, and the overall status of the patient are important considerations in selecting appropriate therapy. Although the specific role of individual agents may vary, hydration remains the cornerstone of therapy. NaCl 0.9%, calcitonin, and Pamidronate disodium have established roles as dominant first-line agents for the management of acute hypercalcemia associated with malignancy.

From mesenchymal stem cells and stromal cells - from bench to bedside

2019 ◽  
Vol 1 (1) ◽  
pp. 36-39
Author(s):  
Bernd Giebel ◽  
Verena Börger ◽  
Mario Gimona ◽  
Eva Rohde
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Stromal Cells ◽  
Therapeutic Agent ◽  
Therapeutic Potential ◽  
Therapeutic Effects ◽  
Cell Replacement ◽  
Beneficial Effects ◽  
Promising Tool

Human mesenchymal stem/stromal cells (MSCs) represent a promising tool in regenerative medicine. Until now, almost one thousand NIH-registered clinical trials investigated their immunomodulatory and pro-regenerative therapeutic potential in various diseases. Despite controversial reports regarding the efficacy of MSC-treatments, MSCs appear to exert their beneficial effects in a paracrine manner rather than by cell replacement. In this context, extracellular vesicles (EVs), such as exosomes and microvesicles, seem to induce the MSCs’ therapeutic effects. Here, we briefly illustrate the potential of MSC-EVs as therapeutic agent of the future.

Leukotriene-Receptor Antagonists and 5-Lipoxygenase Inhibitors in Asthma

1993 ◽  
Vol 27 (7-8) ◽  
pp. 898-903 ◽  
Author(s):  
Julie S. Larsen ◽  
Edward P. Acosta
Keyword(s):  
Clinical Trials ◽  
English Language ◽  
Data Extraction ◽  
Background Information ◽  
Receptor Antagonists ◽  
Lipoxygenase Inhibitors ◽  
Medline Search ◽  
Leukotriene Receptor Antagonists ◽  
Patient Tolerance ◽  
Leukotriene Receptor

OBJECTIVE: To familiarize readers with a potentially new class of compounds for treating asthma. Background information on leukotrienes is provided in addition to an indepth review of pertinent clinical trials. DATA SOURCES: Information was obtained from controlled clinical trials, abstracts, and review articles identified through a MEDLINE search of English-language articles. STUDY SELECTION: Emphasis was placed on early clinical trials that showed some benefit with these compounds as well as more recent studies using newer agents that produced more promising results. DATA EXTRACTION: Information regarding leukotriene biochemistry was extracted from basic science research and data from human studies were evaluated by the authors according to patient selection, study design, methodology, and therapeutic response. DATA SYNTHESIS: Leukotrienes have a pathophysiologic role in asthma. Two distinct but pharmacologically similar classes of leukotriene inhibitors are currently being clinically evaluated. These are leukotriene receptor antagonists and 5-lipoxygenase inhibitors. Early clinical trials with these agents yielded unfavorable results primarily because of lack of drug potency and selectivity, poor patient tolerance, and possibly the route of administration. Subsequent studies with more potent and selective agents have further implicated leukotrienes as biochemical mediators in asthma and, consequently, have shown promising clinical outcomes with respect to pulmonary function testing and patient tolerance. CONCLUSIONS: Advancements in the pathogenesis of asthma are beginning to define a role for the leukotrienes. Although more studies are needed to assess the efficacy of leukotriene inhibitors, recent clinical trials using leukotriene-receptor antagonists and 5-lipoxygenase inhibitors indicate a potential for the expansion of therapeutic regimens currently used in the treatment of asthma.

Ticlopidine and Antiplatelet Therapy

1993 ◽  
Vol 27 (9) ◽  
pp. 1090-1098 ◽  
Author(s):  
Patricia Flores-Runk ◽  
Ralph H. Raasch
Keyword(s):  
Clinical Trials ◽  
English Language ◽  
Data Extraction ◽  
Artery Bypass ◽  
Antiplatelet Agent ◽  
Antiplatelet Agents ◽  
Graft Patency ◽  
Diabetic Microangiopathy ◽  
Severe Reaction ◽  
English Language Journal

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical efficacy, and toxicity of ticlopidine. Comparisons with other antiplatelet agents are presented, with an emphasis on efficacy, and a recommendation is provided regarding ticlopidine's place in therapy. DATA SOURCES: A MEDLINE literature retrieval of English-language journal articles from 1987 to January 1993 and references identified from bibliographies of review articles and clinical trials. STUDY SELECTION: Randomized, blind, controlled studies of ticlopidine and other antiplatelet agents were preferentially selected. DATA EXTRACTION: Clinical trials were reviewed in terms of study design, efficacy results, and toxicity. DATA SYNTHESIS: Ticlopidine is a new antiplatelet agent with a distinct mechanism of action. In the largest trial of the drug for the prevention of stroke, it was found to be more effective than aspirin in reducing the risk of stroke or death. Clinical trials have also shown ticlopidine to decrease the rate of vascular death and myocardial infarction in patients with unstable angina, and to maintain venous graft patency after coronary artery bypass grafting. The use of ticlopidine in diabetic microangiopathy and peripheral vascular disease appears promising, but further studies are needed. Adverse reactions most commonly reported with ticlopidine are gastrointestinal complaints; the most severe reaction is transient neutropenia, which is seen in approximately 2.3 percent of patients and is severe in nearly 1 percent. CONCLUSIONS: Ticlopidine is a reasonable alternative for use in preventing stroke among patients unable to take aspirin or those who do not benefit from aspirin therapy. Its use as first-line therapy is limited by its high cost and the occurrence of hematologic adverse effects.

scholarly journals Safety and Effectiveness of Favipiravir for Novel Coronavirus (COVID-19): A Rapid Review of Available Evidence

2021 ◽  
Author(s):  
Mohammadreza Mobinizadeh ◽  
Morteza Arab-Zozani
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Therapeutic Potential ◽  
Data Extraction ◽  
Rapid Review ◽  
Eligibility Criteria ◽  
Clinical Trial Registration ◽  
Registration System ◽  
Novel Coronavirus ◽  
First Time

Context: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appeared for the first time in December 2019 in Wuhan, China. Due to the lack of unified and integrated evidence for Favipiravir, this study was conducted to rapidly review the existing evidence to help evidence-based decision-making on the therapeutic potential of this drug in the treatment of COVID-19 patients. Evidence Acquisition: This study is a rapid Health Technology Assessment (HTA). By searching pertinent databases, the research team collected relevant articles and tried to create a policy guide through a thematic approach. This rapid review was done in four steps: (1) Searching for evidence through databases; (2) screening the evidence considering eligibility criteria; (3) data extraction; and (4) analyzing the data through thematic analysis. Results: After applying the inclusion criteria, four studies were finally found, including three review studies and a clinical trial that was temporarily removed by its publisher from the journal’s website. After searching the sources mentioned in the articles, two ongoing clinical trials were found in China. Also, by searching the clinical trial website, www.clinicaltrials.gov, five clinical trials were found in the search. The result of the search in the clinical trial registration system in Iran showed a study that is in the process of patient recruitment. A limited number of other articles were found, mostly in the form of reflections from physicians or researchers and letters to editors who have predicted the drug’s performance on SARS-CoV-2, which needs further clinical study to be approved. Conclusions: With the available evidence, it is not possible to make a definite conclusion about the safety and efficacy of Favipiravir in the treatment of patients with COVID-19.

Sign in / Sign up

Export Citation Format

Share Document