Calcium-Channel Antagonists for Prevention of Atherosclerosis

1993 ◽  
Vol 27 (1) ◽  
pp. 61-67 ◽  
Author(s):  
Shawn M. Borcherding ◽  
Suzanne G. Meeves ◽  
Neil E. Klutman ◽  
Patricia A. Howard
Keyword(s):  
Clinical Trials ◽  
Calcium Channel ◽  
Calcium Antagonists ◽  
Clinical Studies ◽  
Animal Studies ◽  
English Language ◽  
Data Extraction ◽  
Calcium Channel Antagonists ◽  
Trial Duration

OBJECTIVE: To critically evaluate the current literature regarding the role of calcium-channel antagonists in preventing atherosclerosis. DATA SOURCES: English language clinical studies, abstracts, conference proceedings, and review articles pertaining to calcium-channel antagonists and atherosclerosis. STUDY SELECTION: Relevant animal and human studies examining the role of calcium-channel antagonists in atherosclerosis prevention and treatment. DATA EXTRACTION: Potential mechanisms for the development of atherosclerosis and the use of calcium antagonists for preventing and treating coronary artery disease are discussed. Animal studies are summarized; next, significant data from human clinical studies are presented. DATA SYNTHESIS: Available studies are described and discussed. CONCLUSIONS: Results from animal and clinical trials in humans suggest that calcium antagonists may retard the development and progression of atherosclerosis. However, most clinical trials to date have been conducted in patients with proven atherosclerotic plaques. Further studies examining the role of calcium-channel antagonists in preventing and treating atherosclerosis are needed, but may be difficult to conduct because of the large numbers of patients required, long trial duration, and associated costs.

MenQuadfi (MenACWY-TT): A New Vaccine for Meningococcal Serogroups ACWY

2021 ◽  
pp. 106002802110398
Author(s):  
Jessica Huston ◽  
Kevin Galicia ◽  
Eric F. Egelund
Keyword(s):  
Phase Ii ◽  
Meningococcal Disease ◽  
Clinical Studies ◽  
Animal Studies ◽  
English Language ◽  
Data Extraction ◽  
Relevant Literature ◽  
The United States ◽  
Phase Iii ◽  
Efficacy And Safety

Objective This article reviews data encompassing the pharmacology, efficacy, and safety of MenACWY-TT (MenQuadfi), a conjugate vaccine to prevent meningococcal disease from serogroups A, C, W, Y. Data Sources A literature review was conducted in PubMed, MEDLINE, and ClinicalTrials.gov from inception up to July 2021, using the search terms MenQuadfi, meningococcal ACWY vaccine, MCV4, and menacwy. Articles from reference lists were included to identify potential relevant literature. Study Selection and Data Extraction Data were limited to randomized phase II and III clinical studies published in the English language, evaluating the efficacy and safety of MenACWY-TT. Animal studies and studies not utilizing MenACWY-TT were excluded. Data Synthesis One phase II and 4 phase III randomized clinical studies, enrolling approximately 7700 participants, aged 2 years to 97 years old found that MenACWY-TT was noninferior when compared to established MenACWY vaccines, as measured by surrogate immunogenicity end points. In studies evaluating primary dose vaccination, conducted in those aged 2 to 97 years of age, the difference in seroresponse rates, reported by the lower bound of the 95% CI, was (A) 1.1% to 14.8%, (C) 21% to 42.2%, (Y) 7.7% to 24.6%, and (W) 8.9% to 22.5%. Relevance to Patient Care and Clinical Practice Despite the low incidence of meningococcal disease in the United States, meningococcal disease causes significant morbidity and mortality if not prevented. Conclusion MenACWY-TT is noninferior to currently approved quadrivalent meningococcal vaccines and shows similar immunogenicity and safety as both an initial vaccine for prevention as well as a booster dose.

Levoleucovorin as Replacement for Leucovorin in Cancer Treatment

2012 ◽  
Vol 46 (10) ◽  
pp. 1349-1357 ◽  
Author(s):  
Victor Tuan Giam Chuang ◽  
Manabu Suno
Keyword(s):  
Clinical Trials ◽  
Cancer Treatment ◽  
Clinical Studies ◽  
English Language ◽  
Antitumor Agents ◽  
Data Extraction ◽  
Phase 1 ◽  
Phase 3 ◽  
Medline Search ◽  
Reasonable Alternative

Objective: To comprehensively review the literature regarding the efficacy, safety, and costs associated with the use of levoleucovorin in cancer treatment and to assess whether levoleucovorin would be a reasonable alternative to the use of racemic leucovorin. Data Sources: A MEDLINE search was conducted for English-language human studies published between January 1980 and April 2012 using the terms I-LV. levoleucovorin, d,I-LV, leucovorin, folinic acid, tolinate, 5-formyltetrahydrofolate, folic acid, folates, methotrexate, 5-fluorouracil, and clinical trials. Study Selection and Data Extraction: Articles pertinent to clinical trials (Phase 1, 2, 3) related to evaluating the efficacy, interchangeability, and safety of levoleucovorin were collected and their contents reviewed. Data Synthesis: From these pharmacokinetics and clinical studies, information on the use of levoleucovorin as a modulator of fluorouracil as well as when combined with other antitumor agents were scrutinized and extracted for comparison with leucovorin whenever possible. Two randomized Phase 3 clinical studies comparing the efficacy and adverse effect profiles of leucovorin and levoleucovorin demonstrated that levoleucovorin is as effective as leucovorin in terms of response, toxicity, and survival. Six randomized Phase 3 clinical studies demonstrated the safety and efficacy of levoleucovorin as a modulator of fluorouracil in combination with/without other antitumor agents in colorectal cancer patients. Levoleucovorin has been studied in other cancers. These clinical Phase 1/2/3 studies demonstrated efficacy and safety of levoleucovorin in combination chemotherapeutic regimens comprising fluorouracil and other antitumor agents. Conclusions: The results of the clinical studies suggest that levoleucovorin is efficacious and can be used safely in combination with fluorouracil and other antitumor agents. Levoleucovorin can be used interchangeably with leucovorin for modulating fluorouracil. The current shortage of the supply of leucovorin centered in North America renders levoleucovorin a reasonable alternative in terms of efficacy and toxicity profile, but from the perspective of cost, leucovorin remains the drug of choice.

The New Macrolide Antibiotics: Azithromycin, Clarithromycin, Dirithromycin, and Roxithromycin

1992 ◽  
Vol 26 (1) ◽  
pp. 46-55 ◽  
Author(s):  
Neeta Bahal ◽  
Milap C. Nahata
Keyword(s):  
Clinical Trials ◽  
English Language ◽  
Data Extraction ◽  
Macrolide Antibiotics ◽  
Data Synthesis ◽  
Antimicrobial Spectrum ◽  
Study Selection ◽  
Frequent Administration ◽  
Elimination Half

OBJECTIVE: To review the chemistry, antimicrobial spectrum, pharmacokinetics, clinical trials, adverse effects, and drug interactions of four new macrolide antibiotics: Azithromycin, clarithromycin, dirithromycin, and roxithromycin. DATA SOURCES: Information was obtained from comparative clinical trials, abstracts, conference proceedings, and review articles. Indexing terms included azithromycin, clarithromycin, dirithromycin, erythromycin, roxithromycin, and macrolide antibiotics. STUDY SELECTION: Emphasis was placed on comparative clinical trials involving the new macrolide antibiotics. DATA EXTRACTION: Data from human studies published in the English language were evaluated. Trials were assessed by sample size, macrolide dosage regimen, and therapeutic response. DATA SYNTHESIS: The erythromycins have gained widespread use in treating a variety of infections. Although they are effective, limitations include the need to administer four times a day and the intolerable adverse gastrointestinal effects. Four of the more extensively studied agents, azithromycin, clarithromycin, dirithromycin, and roxithromycin, are currently being studied in patients. Based on the studies to date, the newer macrolides may offer several advantages over erythromycin, including: (1) greater antimicrobial activity against certain organisms; (2) longer elimination half-life, thus allowing less frequent administration; and (3) lower incidence of adverse gastrointestinal effects. CONCLUSIONS: The new macrolide antibiotics appear to offer an improvement over erythromycin. Definitive conclusions about the role of these drugs should await completion of ongoing clinical studies.

Role of Acetyl-L-Carnitine in the Treatment of Diabetic Peripheral Neuropathy

2008 ◽  
Vol 42 (11) ◽  
pp. 1686-1691 ◽  
Author(s):  
Jeffery D Evans ◽  
Tibb F Jacobs ◽  
Emily W Evans
Keyword(s):  
Clinical Trials ◽  
Peripheral Neuropathy ◽  
Diabetic Peripheral Neuropathy ◽  
English Language ◽  
Data Extraction ◽  
Disease Process ◽  
Medline Search ◽  
Treatment And Prevention ◽  
Meta Analyses

Objective: To examine the role of acetyl-L-carnitine (ALC) in the treatment of diabetic peripheral neuropathy (DPN). Data Sources: A MEDLINE search (1966–April 2008) of the English-language literature was performed using the search terms carnitine, diabetes, nerve, and neuropathy. Studies identified were then cross-referenced for their citations. Study Selection and Data Extraction: The search was limited to clinical trials, meta-analyses, and reviews addressing the use of ALC for the treatment of DPN. Studies that included other disease states that could cause peripheral neuropathy were excluded. Two large clinical studies that used ALC for the treatment of DPN were identified. No case studies were identified. Data Synthesis: The results from 2 published clinical trials Involving 1679 subjects were included. Subjects who received at least 2 g daily of ALC showed decreases in pain scores. One study showed improvements in electrophysiologic factors such as nerve conduction velocities, while the other did not. Patients who had neuropathic pain reported reductions in pain using a visual analog scale. Nerve regeneration was documented in one trial. The supplement was well tolerated, A proprietary form of ALC was used in both studies. Conclusions: Data on treatment of DPN with ALC support its use. It should be recommended to patients early in the disease process to provide maximal benefit. Further studies should be conducted to determine the effectiveness of ALC in the treatment and prevention of the worsening symptoms of DPN.

Renal and Cardiac Implications of Sodium Glucose Cotransporter 2 (SGLT2) Inhibitors: The State of the Science

2018 ◽  
Vol 52 (12) ◽  
pp. 1238-1249 ◽  
Author(s):  
Joseph E. Cruz ◽  
Tania Ahuja ◽  
Mary Barna Bridgeman
Keyword(s):  
Clinical Trials ◽  
Renal Disease ◽  
English Language ◽  
Disease Risk ◽  
Data Extraction ◽  
Drug Approval ◽  
Sglt2 Inhibitors ◽  
Glucose Levels ◽  
Sodium Glucose Cotransporter

Objective: To review the role of the sodium-glucose cotransporter-2 (SGLT2) inhibitors in the management of type 2 diabetes (T2DM), including the effects on renal and cardiovascular (CV) outcomes. Data Sources: A literature search of MEDLINE databases (1964 through May 2018) was conducted utilizing key words sodium-glucose co-transporter-2 inhibitors, SGLT2 inhibitors, and diabetes; additional limits for drug names were added. Study Selection and Data Extraction: Available English-language data from reviews, abstracts, presentations, and clinical trials of use of SGLT2 therapy specifically detailing outcomes on CV and renal disease in humans were reviewed. Data Synthesis: This review will explore the role of the SGLT2 inhibitors on CV and renal outcomes in patients with T2DM. Relevance to Patient Care and Clinical Practice: A paradigm shift regarding the regulation of medications for the treatment of T2DM has resulted in the need for CV outcomes data as part of the drug approval process. Reduction of major CV events and progression of nephropathy in patients with T2DM represent major outcomes of clinical significance. Few medications have been able to establish a reduction in these end points; data for the use of SGLT2 inhibitors are favorable in this regard. Conclusion: The SGLT2 inhibitors represents a class of medications that reduce glucose levels via a novel and complementary mechanism. Emerging evidence suggests a plausible explanation for the observed reduction in adverse renal and CV outcomes in recent clinical trials. Questions remain whether these agents reduce renal disease risk greater than achievement of the same glycemic goals as other antidiabetics and whether CV and renal benefits are reproducible in high-risk patients with chronic kidney disease.

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.

Role of Ambrisentan in the Management of Pulmonary Hypertension

2008 ◽  
Vol 42 (11) ◽  
pp. 1653-1659 ◽  
Author(s):  
Sandra L Hrometz ◽  
Kelly M Shields
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
English Language ◽  
Data Extraction ◽  
Information Service ◽  
Study Selection ◽  
Pulmonary Arterial ◽  
Improve Exercise Capacity

Objective: To review the role of ambrisentan in the treatment of pulmonary arterial hypertension (PAH). Data Sources: Literature was accessed through MEDLINE (1950-June 2008), Iowa Drug Information Service (1966–March 2008), EMBASE (1966-June 2008), bibliographies of pertinent articles, and unpublished data provided by the manufacturer and the Food and Drug Administration (FDA). Search terms included ambrisentan, endothelin antagonist, pulmonary hypertension, and pulmonary arterial hypertension. Due to limited literature available, additional criteria to limit searches were not used. Study Selection and Data Extraction: Abstracts and original preclinical and clinical research reports available in the English language were Identified for review. All manufacturer-provided data were also evaluated. Literature related to ambrisentan, endothelin antagonists, pulmonary hypertension, and pulmonary arterial hypertension were included. Four clinical trials evaluated the efficacy of ambrisentan in adults with symptomatic PAH. Data Synthesis: Ambrisentan is the latest endothelin-receptor antagonist (ERA) to obtain FDA approval for the treatment of PAH. It joins the first FDA-approved ERA, bosentan. Like bosentan, ambrisentan is available orally (with once-daily dosing compared with bosentan's twice-daily dosing) and has been shown to improve exercise capacity and delay clinical worsening. As with bosentan, the most significant safety concerns with ambrisentan relate to potential liver injury and a contraindication in pregnancy. Although ambrisentan has higher affinity for the endothelin type A receptor than for the endothelin type B receptor, specific advantages of this selectivity, in terms of efficacy compared with bosentan, a nonselective agent, have not been demonstrated. Conclusions: Ambrisentan has been shown to be an effective ERA in patients with PAH. A significant advantage of ambrisentan is the lack of any clinically important drug interactions with warfarin and sildenafil, which are frequently used by patients being treated for PAH.

Lactulose in the Management of Constipation: A Current Review

1992 ◽  
Vol 26 (10) ◽  
pp. 1277-1282 ◽  
Author(s):  
Theresa V. Kot ◽  
Ngaire A. Pettit-Young
Keyword(s):  
Clinical Trials ◽  
Adverse Effects ◽  
Clinical Studies ◽  
Data Extraction ◽  
Point Of View ◽  
Data Synthesis ◽  
Study Selection ◽  
Beneficial Response ◽  
A Current

OBJECTIVE: To review the current published clinical studies evaluating the clinical efficacy and safety of lactulose compared with other laxatives or placebo. Adverse effects associated with lactulose are also reported. DATA SOURCES: Information was retrieved by searching the MEDLINE and EMBASE databases for clinical trials, abstracts, conference proceedings, and review articles dealing with lactulose. STUDY SELECTION: Emphasis was placed on clinical trials where lactulose was compared with other laxatives or placebo in patient populations where the diagnosis of constipation was reasonably established. DATA EXTRACTION: The methodology and results from clinical studies were evaluated. Assessment of the studies was made based on diagnosis of constipation, prior management of patients, follow-up of patients, dosage, and adverse effects. DATA SYNTHESIS: Clinical trials in geriatric patients, terminally ill patients, children, and normal and constipated subjects were reviewed. In most instances, lactulose was compared with a placebo, without incorporating the current education on dietary techniques for improving defecation. CONCLUSIONS: Generally, clinical trials have demonstrated a beneficial response compared with placebo, although sometimes that response has been only marginally better, from a clinical point of view.

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