scholarly journals Adopting an Orphan Drug: Rufinamide for Lennox–Gastaut Syndrome

2009 ◽  
Vol 9 (3) ◽  
pp. 72-74 ◽  
Author(s):  
Susan T. Herman
Keyword(s):  
Seizure Frequency ◽  
Therapy Group ◽  
Controlled Trial ◽  
Treatment Options ◽  
Baseline Period ◽  
Epilepsy Syndrome ◽  
Pediatric Epilepsy ◽  
Percentage Reduction ◽  
Double Blind ◽  
Median Percentage

Rufinamide for Generalized Seizures Associated with Lennox–Gastaut Syndrome. Glauser T, Kluger G, Sachdeo R, Krauss G, Perdomo C, Arroyo S. Neurology 2008;70(21):1950–1958. BACKGROUND: Lennox–Gastaut syndrome is a catastrophic pediatric epilepsy syndrome characterized by multiple types of treatment-resistant seizures and high rates of seizure-related injury. Current available treatments are inadequate, leaving patients with few treatment options and opportunities. METHODS: We conducted a double-blind, randomized, placebo-controlled trial of the antiepileptic drug rufinamide in patients with Lennox–Gastaut syndrome. Eligible patients between 4 and 30 years of age had multiple types of seizures (including tonic–atonic and atypical absence seizures) with a minimum of 90 seizures in the month before baseline and a recent history of a slow spike-and-wave pattern on EEG. RESULTS: After a 28-day baseline period, 139 eligible patients were randomized; 138 patients received either rufinamide (n = 74) or placebo (n = 64) in addition to their other antiepileptic drugs. The median percentage reduction in total seizure frequency was greater in the rufinamide therapy group than in the placebo group (32.7% vs 11.7%, p = 0.0015). There was a difference ( p < 0.0001) in tonic–atonic (“drop attack”) seizure frequency with rufinamide (42.5% median percentage reduction) vs placebo (1.4% increase). The rufinamide group had a greater improvement in seizure severity ( p = 0.0041) and a higher 50% responder rate compared with placebo for total seizures ( p = 0.0045) and tonic–atonic seizures ( p = 0.002). The common adverse events (reported by 10% of patients receiving rufinamide) were somnolence (24.3% with rufinamide vs 12.5% with placebo) and vomiting (21.6% vs 6.3%). CONCLUSIONS: Rufinamide was an effective and well-tolerated treatment for seizures associated with Lennox–Gastaut syndrome.

scholarly journals Pregabalin: The Next New Thing

2005 ◽  
Vol 5 (6) ◽  
pp. 217-219 ◽  
Author(s):  
Edward Faught
Keyword(s):  
Seizure Frequency ◽  
Adjunctive Therapy ◽  
Clinical Laboratory ◽  
Controlled Trial ◽  
Similar Efficacy ◽  
Partial Epilepsy ◽  
Laboratory Evaluation ◽  
Double Blind ◽  
Median Percentage ◽  
Baseline Phase

Safety and Efficacy of Two Pregabalin Regimens for Add-on Treatment of Partial Epilepsy Beydoun A, Uthman BM, Kugler AR, Greiner MJ, Knapp LE, Garofalo EA; Pregabalin 1008-009 Study Group Neurology 2005;64:475–480 Objective To evaluate the efficacy, tolerability, and safety of two pregabalin regimens administered as adjunctive therapy to that of placebo in patients with medically refractory partial epilepsy. Methods A multicenter, double-blind, randomized, parallel-group, placebo-controlled trial was performed. After a prospective 8-week baseline phase, patients were randomized to 12 weeks of double-blind treatment with placebo or pregabalin, 600 mg/day, administered twice daily (BID) or 3 times daily (TID). Primary efficacy was measured as change in seizure frequency from baseline of either pregabalin regimen compared with placebo. Secondary efficacy comparisons included the proportion of patients experiencing ≥50% reduction in seizure frequency (responder rate) and median percentage change from baseline in seizure frequency. Safety/tolerability assessments included adverse events (AEs), physical and neurologic examinations, and clinical laboratory evaluation. Efficacy and safety analyses were performed on the intent-to-treat (ITT) population. Results Pregabalin treatment resulted in seizure frequency reductions: 53% for pregabalin TID ( P ≤ 0.0001) and 44% for pregabalin BID ( P ≤ 0.0001) compared with a 1% increase for placebo. Responder rates were 49% for pregabalin TID and 43% for pregabalin BID compared with 9% for placebo ( P ≤ 0.001). Both pregabalin regimens were similar in efficacy and tolerability. The most common AEs were dizziness, somnolence, and ataxia. Conclusions Pregabalin administered at 600 mg/day is safe, generally well tolerated, and efficacious as adjunctive therapy for the treatment of patients with partial seizures, with or without secondary generalizations. This dose can be administered on a twice-daily or 3-times-daily schedule with similar efficacy and tolerability results.

scholarly journals Efficacy and tolerability of baclofen in a U.S. community population with alcohol use disorder: a dose-response, randomized, controlled trial

2021 ◽  
Author(s):  
James C. Garbutt ◽  
Alexei B. Kampov-Polevoy ◽  
Cort Pedersen ◽  
Melissa Stansbury ◽  
Robyn Jordan ◽  
...  
Keyword(s):  
Alcohol Use ◽  
Alcohol Use Disorder ◽  
Controlled Trial ◽  
Treatment Options ◽  
Double Blind ◽  
Randomized Controlled ◽  
Main Effect ◽  
Dsm Iv ◽  
Drop Outs ◽  
Positive Effect

AbstractIdentification of new medications for alcohol use disorder (AUD) is important for improving treatment options. Baclofen, a GABAB agonist, has been identified as a potential pharmacotherapy for AUD. In a 16-week double-blind, randomized, placebo-controlled trial, we investigated 30 and 90 mg/day of baclofen compared to placebo and examined effects of dose, sex, and level of pretreatment drinking. One hundred and twenty participants with DSM-IV alcohol dependence (age 46.1 (sd = 10.1) years, 51.7% male) were randomized after exclusion for unstable medical/psychiatric illness and/or dependence on drugs other than nicotine. Seventy-three participants completed the trial. A main effect of baclofen was found [%HDD (F(2,112) = 4.16, p = 0.018, d = 0.51 95%CI (0.06–0.95), 13.6 fewer HDD) and %ABST (F(2,112) = 3.68, p = 0.028, d = 0.49 95%CI (0.04–0.93), 12.9 more abstinent days)] and was driven by the 90 mg/day dose. A sex × dose interaction effect was present for both %HDD (F(2,110) = 5.48, p = 0.005) and %ABST (F(2,110) = 3.19, p = 0.045). Men showed a marginally positive effect for 90 mg/day compared to PBO (%HDD t(110) = 1.88, p = 0.063, d = 0.36 95%CI (−0.09–0.80), 15.8 fewer HDD days; %ABST t(110) = 1.68 (p = 0.096, d = 0.32 95%CI (−0.12–0.76), 15.7 more ABST)) with no effect for 30 mg/day. Women showed a positive effect for 30 mg/day (%HDD, t(110) = 3.19, p = 0.002, d = 0.61 95%CI (0.16–1.05), 26.3 fewer HDD days; %ABST t(110) = 2.73, p = 0.007, d = 0.52 95%CI (0.07–0.96), 25.4 more ABST days) with marginal effects for 90 mg/day on %ABST (p = 0.06) with drop-outs/dose reduction from sedative side-effects of 59% in women at 90 mg/day compared to 5% for men. These findings support the hypothesis that baclofen has efficacy in AUD and suggest that dose and sex be further explored as potential moderators of baclofen response and tolerability.

Behavioral interventions as a treatment for epilepsy

Neurology ◽  
2018 ◽  
Vol 90 (11) ◽  
pp. e963-e970 ◽  
Author(s):  
Sheryl R. Haut ◽  
Richard B. Lipton ◽  
Susannah Cornes ◽  
Alok K. Dwivedi ◽  
Rachel Wasson ◽  
...  
Keyword(s):  
Seizure Frequency ◽  
Stress Reduction ◽  
Behavioral Interventions ◽  
Focal Epilepsy ◽  
Muscle Relaxation ◽  
Baseline Period ◽  
Progressive Muscle Relaxation ◽  
Focused Attention ◽  
Electronic Diary ◽  
Double Blind

ObjectiveTo evaluate the effect of a stress-reduction intervention in participants with medication-resistant epilepsy.MethodsAdults with medication-resistant focal epilepsy (n = 66) were recruited from 3 centers and randomized to 1 of 2 interventions: (1) progressive muscle relaxation (PMR) with diaphragmatic breathing, or (2) control focused-attention activity with extremity movements. Following an 8-week baseline period, participants began 12 weeks of double-blind treatment. Daily self-reported mood and stress ratings plus seizure counts were completed by participants using an electronic diary, and no medication adjustments were permitted. The primary outcome was percent reduction in seizure frequency per 28 days comparing baseline and treatment; secondary outcomes included stress reduction and stress–seizure interaction.ResultsIn the 66 participants in the intention-to-treat analysis, seizure frequency was reduced from baseline in both treatment groups (PMR: 29%, p < 0.05; focused attention: 25%, p < 0.05). PMR and focused attention did not differ in seizure reduction (p = 0.38), although PMR was associated with stress reduction relative to focused attention (p < 0.05). Daily stress was not a predictor of seizures.ConclusionsBoth PMR and the focused-attention groups showed reduced seizure frequency compared to baseline in participants with medication-resistant focal seizures, although the 2 treatments did not differ. PMR was more effective than focused attention in reducing self-reported stress.ClinicalTrials.gov identifierNCT01444183.

The Effect of Oral Niacinamide on Plasma Phosphorus Levels in Peritoneal Dialysis Patients

2009 ◽  
Vol 29 (5) ◽  
pp. 562-567 ◽  
Author(s):  
Daniel O. Young ◽  
Steven C. Cheng ◽  
James A. Delmez ◽  
Daniel W. Coyne
Keyword(s):  
Peritoneal Dialysis ◽  
Adverse Effects ◽  
Controlled Trial ◽  
Treatment Options ◽  
Study Drug ◽  
Phosphate Binders ◽  
Open Label ◽  
Double Blind ◽  
Phosphorus Levels ◽  
Plasma Phosphorus

Background Hyperphosphatemia remains a significant problem for patients requiring dialysis and is associated with increased mortality. Current treatment options include dietary restriction, dialysis, and phosphate binders. Treatment using the latter is frequently limited by cost, tolerability, and calcium loading. One open-label trial found niacinamide to be effective at decreasing serum phosphorus values in hemodialysis patients. Niacinamide may effectively reduce phosphorus levels in peritoneal dialysis (PD) patients already receiving standard phosphorus-lowering therapies. Methods An 8 week, randomized, double blind, placebo-controlled trial to evaluate the effectiveness of niacinamide to reduce plasma phosphorus levels in PD patients. Patients had to demonstrate a baseline phosphorus value > 4.9 mg/dL. Patients were randomized to niacinamide or placebo and prescribed 250 mg twice daily, with titration to 750 mg twice daily, as long as safety parameters were not violated. Phosphate binders, active vitamin D, and cinacalcet were kept constant during the study. The primary end point was change in plasma phosphorus. Secondary end points included changes in lipid parameters. Results 15 patients started on the study drug (8 niacinamide, 7 placebo) and 7 in each arm had at least one on-study phosphorus measurement. The niacinamide treatment group experienced an average 0.7 ± 0.9 mg/dL decrease in plasma phosphorus and the placebo-treated group experienced an average 0.4 ± 0.8 mg/dL increase. The treatment effect difference (1.1 mg/dL) was significant ( p = 0.037). No significant changes in high- or low-density lipoproteins or triglycerides were demonstrated. Two of the 8 patients randomized to the niacinamide treatment arm had to withdraw from the study due to drug-related adverse effects. Adverse effects may limit the use of niacinamide in PD patients. Conclusion Niacinamide, when added to standard phosphorus-lowering therapies, resulted in a modest yet statistically significant reduction in plasma phosphorus levels at 8 weeks. [ClinicalTrials.gov number NCT00508885 (ClinicalTrials.gov)]

scholarly journals 2226. Impact of Prior and Concomitant Antibacterial Therapy on Outcomes in the ASPECT-NP Randomized, Controlled Trial of Ceftolozane/Tazobactam (C/T) vs. Meropenem (MEM) in Patients with Ventilated Nosocomial Pneumonia (NP)

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S760-S760
Author(s):  
Richard G Wunderink ◽  
Christopher Bruno ◽  
Ignacio Martin-Loeches ◽  
Marin Kollef ◽  
Jean-Francois Timsit ◽  
...  
Keyword(s):  
Antibacterial Therapy ◽  
Controlled Trial ◽  
Treatment Options ◽  
Study Drug ◽  
Drug Susceptibility ◽  
Double Blind ◽  
Gram Negative ◽  
Randomized Controlled ◽  
Secondary Endpoints ◽  
The Impact

Abstract Background NP is a frequent healthcare-acquired infection associated with high mortality; rising resistance rates among causative Gram-negative pathogens require new treatment options. In the randomized, controlled, double-blind, phase 3 ASPECT-NP trial, C/T (at double the initially approved dose) was noninferior to MEM for ventilated NP in both primary and key secondary endpoints. Here we evaluate the impact of prior and concomitant Gram-negative antibacterial therapy on outcomes in that trial. Methods Mechanically ventilated patients with ventilator-associated or hospital-acquired pneumonia were randomized 1:1 to 3 g C/T or 1 g MEM, both by 1-h IV infusion every 8 hours for 8–14 days. Patients could receive ≤24 hours of active antibacterial therapy within ≤72 hours prior to first dose; longer durations were permitted in case of prior treatment failure (i.e., signs and/or symptoms of the current episode of ventilated NP persisted/worsened despite ≥48 hours of treatment). At sites with MEM-resistant Pseudomonas aeruginosa rates ≥15%, patients could optionally receive up to 72 h of adjunctive empiric aminoglycoside (amikacin was recommended) until study drug susceptibility was confirmed. Primary and key secondary endpoints, respectively, were 28-d all-cause mortality and clinical response at test of cure (TOC; 7–14 days after the end of therapy) in the intent to treat (ITT) population (all randomized patients). Results In the C/T arm, 285/362 (79%) ITT patients received prior systemic Gram-negative therapy and 103/362 (28%) received adjunctive aminoglycoside, compared with 288/364 (79%) and 112/364 (31%) patients, respectively, in the MEM arm. In the microbiologic ITT population, causative pathogens in patients failing prior therapy at the time of enrollment (C/T 15%, MEM 11%) were mainly Klebsiella spp (33%), P. aeruginosa (17%), Escherichia coli (14%), and Acinetobacter baumannii (8%). Mortality and cure rates were comparable between C/T and MEM regardless of receipt of prior systemic or adjunctive Gram-negative therapy (table). Conclusion Prior and adjunctive Gram-negative antibacterial therapy did not affect the relative efficacy of C/T (at the 3-g dose) vs. MEM in these high-risk patients with Gram-negative ventilated NP. Disclosures All authors: No reported disclosures.

scholarly journals Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: a phase 3 randomized placebo-controlled trial

Blood ◽  
2020 ◽  
Vol 135 (24) ◽  
pp. 2137-2145 ◽  
Author(s):  
Andrew H. Wei ◽  
Pau Montesinos ◽  
Vladimir Ivanov ◽  
Courtney D. DiNardo ◽  
Jan Novak ◽  
...  
Keyword(s):  
Remission Rate ◽  
Controlled Trial ◽  
Treatment Options ◽  
Intensive Chemotherapy ◽  
Newly Diagnosed ◽  
Primary Analysis ◽  
Phase 3 ◽  
Double Blind ◽  
Meaningful Improvement ◽  
Risk Of Death

Abstract Effective treatment options are limited for patients with acute myeloid leukemia (AML) who cannot tolerate intensive chemotherapy. Adults age ≥18 years with newly diagnosed AML ineligible for intensive chemotherapy were enrolled in this international phase 3 randomized double-blind placebo-controlled trial. Patients (N = 211) were randomized 2:1 to venetoclax (n = 143) or placebo (n = 68) in 28-day cycles, plus low-dose cytarabine (LDAC) on days 1 to 10. Primary end point was overall survival (OS); secondary end points included response rate, transfusion independence, and event-free survival. Median age was 76 years (range, 36-93 years), 38% had secondary AML, and 20% had received prior hypomethylating agent treatment. Planned primary analysis showed a 25% reduction in risk of death with venetoclax plus LDAC vs LDAC alone (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.52-1.07; P = .11), although not statistically significant; median OS was 7.2 vs 4.1 months, respectively. Unplanned analysis with additional 6-month follow-up demonstrated median OS of 8.4 months for the venetoclax arm (HR, 0.70; 95% CI, 0.50-0.98; P = .04). Complete remission (CR) plus CR with incomplete blood count recovery rates were 48% and 13% for venetoclax plus LDAC and LDAC alone, respectively. Key grade ≥3 adverse events (venetoclax vs LDAC alone) were febrile neutropenia (32% vs 29%), neutropenia (47% vs 16%), and thrombocytopenia (45% vs 37%). Venetoclax plus LDAC demonstrates clinically meaningful improvement in remission rate and OS vs LDAC alone, with a manageable safety profile. Results confirm venetoclax plus LDAC as an important frontline treatment for AML patients unfit for intensive chemotherapy. This trial was registered at www.clinicaltrials.gov as #NCT03069352.

Patient evaluation of a physician conveying a more optimistic versus a less optimistic message: A randomized controlled trial.

2014 ◽  
Vol 32 (31_suppl) ◽  
pp. 88-88
Author(s):  
Kimberson Tanco ◽  
Wadih Rhondali ◽  
Pedro Emilio Perez-Cruz ◽  
Silvia Tanzi ◽  
Gary B. Chisholm ◽  
...  
Keyword(s):  
Medical Profession ◽  
Controlled Trial ◽  
Treatment Options ◽  
Univariate Analysis ◽  
Order Effect ◽  
Background Information ◽  
P Value ◽  
Prognostic Information ◽  
Double Blind ◽  
Randomized Controlled

88 Background: Information regarding treatment options and prognosis is essential for patient decision making near end of life. However, physicians are frequently reluctant to deliver bad news due to multiple factors, including fear of being perceived as less compassionate. This randomized controlled double blind trial aimed to examine the patient’s perception of physician compassion after being exposed to a more optimistic vs. a less optimistic message. Methods: 100 patients were randomized to observe 2 standardized videos, depicting a physician discussing treatment and prognostic information (more optimistic message and less optimistic message) with a patient with advanced cancer. Both physicians displayed identical number of empathetic statements (5) and posture. Three sets of surveys were completed including the Physician Compassion Questionnaire (0=best, 50=worst). Actors and patients were blinded to the purpose of the study. Investigators were blinded to the video observed by the patient. Results: Patients reported significantly better compassion scores after watching the more optimistic video as compared to the less optimistic video [median (Q1-Q3): 15 (5-23) vs. 23 (10-31), p=0.0002]. Results were equally significant after parallel analysis of first video only and after cross-over analysis. There was also an order effect with compassion scores (p=0.0002) favoring the second video. Univariate analysis showed that degree of trust in the medical profession, ESAS fatigue, ESAS anxiety and ESAS depression had significant association with compassion perception independent of message observed. After applying Bonferonni correction, only degree of trust in the medical profession reached the corrected p value of p=0.0014 (p=0.0002). Conclusions: A more optimistic message resulted in a physician being perceived as more compassionate by the patient. The physician seen in second order is also perceived to be more compassionate. More research is needed to better understand patient perception of compassion in communication with physicians.

scholarly journals The effect of low-dose potassium supplementation on blood pressure in apparently healthy volunteers

2003 ◽  
Vol 90 (1) ◽  
pp. 53-60 ◽  
Author(s):  
Donald J. Naismith ◽  
Alessandro Braschi
Keyword(s):  
Blood Pressure ◽  
Fruits And Vegetables ◽  
Low Dose ◽  
Urine Analysis ◽  
Controlled Trial ◽  
Substantial Reduction ◽  
Extended Period ◽  
Baseline Period ◽  
Double Blind ◽  
Change In Mean

Epidemiological and clinical trials suggest an inverse relationship between dietary K intake and blood pressure (BP). Most trials however have been of short duration, the dose of K was high, and the results have been conflicting. The aim of the present study was to evaluate the effect on BP of a low-dose supplementation (24 mmol/d) for an extended period. A double-blind placebo-controlled trial was conducted on fifty-nine volunteers, randomly assigned to receive 24 mmol slow-release KC1/d (n 30) or a placebo (n 29). Measures of BP, anthropometric characteristics and urine analysis for electrolytes were recorded during a 1-week baseline period. Supplementation was for 6 weeks during which BP and changes in weight were assessed and a second 24h urine collection made. The primary outcome was the change in mean arterial pressure (MAP); systolic BP(SBP) and diastolic BP(DBP) were secondary outcomes. After 6 weeks of supplementation MAP was reduced by 7·01 (95% CI −9·12, −4·89; P<0·001) mmHg, SBP was reduced by 7·60 (95% CI −10·46, −4·73; P<0·001) mmHg and DBP was reduced by 6·46 (95% CI −8·74, −4·19; P<0·001) mmHg. The reduction in MAP was positively associated with baseline urinary Na:K (P<0·034). A low daily dietary supplement of K, equivalent to the content of five portions of fresh fruits and vegetables, induced a substantial reduction in MAP, similar in effect to single-drug therapy for hypertension.

scholarly journals 808-Nm Near-Infrared Laser Photobiomodulation versus Switched-Off Laser Placebo in Major Aphthae Management: A Randomized Double-Blind Controlled Trial

2021 ◽  
Vol 11 (11) ◽  
pp. 4717
Author(s):  
Claudio Pasquale ◽  
Esteban Colombo ◽  
Stefano Benedicenti ◽  
Antonio Signore ◽  
Andrea Amaroli
Keyword(s):  
Placebo Group ◽  
Near Infrared ◽  
Therapy Group ◽  
Controlled Trial ◽  
Predictor Variable ◽  
Complete Healing ◽  
Treatment Modalities ◽  
Double Blind ◽  
Natural Period ◽  
End Point

Background: the aphtha is one of the most common oral mucosal ulcerations and presents as a painful punched-out sore. Systemic and topical medications are used to reduce inflammation and pain and to support the natural period of remission. Alternative treatment modalities have been requested to relieve pain and improve its healing. In this regard, photobiomodulation, which is a manipulation of cells’ metabolism through an energy transfer by light sources of non-ablative or thermal intensity, could support aphtha management. The predictor variable of our research was the photobiomodulation through higher energy and power irradiated through a handpiece with a flat-top beam profile. The primary end point was the complete healing of the aphtha, defined as the time from the irradiation to the complete recovery. The secondary end point was pain relief, evaluated daily through the visual analogue scale (VAS), from the irradiation to 24 and 48 h after. Methods: a randomized, double-blind, controlled trial was conducted according to the CONSORT guideline. Irradiation was performed through an 808-nm diode laser with flat-top handpiece, and 1 W, 1 W/cm2, 60 J, 60 J/cm2 for 60 s on a spot-size area of 1 cm2. Time of complete healing and pain evaluation by VAS scale were evaluated. Results: between 1 January, 2020 and 1 March, 2021, 126 patients were screened for the study at the Department of Surgical and Diagnostic Sciences, University of Genoa, Italy. Sixty patients were randomly assigned (30 in the photobiomodulation group and 30 in the placebo group). Patients of the photobiomodulation group experienced complete healing in an average time of 8.13 days ± 1.69 (min 5–max 10 days), while for the placebo group the average time extended to 30.76 ± 4.63 days (min 25–max 42 days). Patients of the photobiomodulation therapy group experienced a statistically significant reduction in pain and discomfort 24 and 48 h after treatment (p < 0.05); the reduction was statistically higher (p < 0.05) 48 h after treatment compared to 24 h after. Conclusions: photobiomodulation at the parameters and modality of irradiation proposed accelerates the healing recovery and reduces pain compared to the patients treated with the placebo.

The Oral Neurokinin-1 Antagonist Aprepitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting: A Multinational, Randomized, Double-Blind, Placebo-Controlled Trial in Patients Receiving High-Dose Cisplatin—The Aprepitant Protocol 052 Study Group

2003 ◽  
Vol 21 (22) ◽  
pp. 4112-4119 ◽  
Author(s):  
Paul J. Hesketh ◽  
Steven M. Grunberg ◽  
Richard J. Gralla ◽  
David G. Warr ◽  
Fausto Roila ◽  
...  
Keyword(s):  
Standard Therapy ◽  
Therapy Group ◽  
Rescue Therapy ◽  
Controlled Trial ◽  
Complete Response ◽  
Nausea And Vomiting ◽  
Phase Iii ◽  
High Dose ◽  
Double Blind ◽  
Double Blind Placebo

Purpose: In early clinical trials with patients receiving highly emetogenic chemotherapy, the neurokinin antagonist aprepitant significantly enhanced the efficacy of a standard antiemetic regimen consisting of a type-three 5-hydroxytryptamine antagonist and a corticosteroid. This multicenter, randomized, double-blind, placebo-controlled phase III study was performed to establish definitively the superiority of the aprepitant regimen versus standard therapy in the prevention of chemotherapy-induced nausea and vomiting (CINV). Patients and Methods: Patients receiving cisplatin ≥ 70 mg/m2 for the first time were given either standard therapy (ondansetron and dexamethasone on day 1; dexamethasone on days 2 to 4) or an aprepitant regimen (aprepitant plus ondansetron and dexamethasone on day 1; aprepitant and dexamethasone on days 2 to 3; dexamethasone on day 4). Patients recorded nausea and vomiting episodes in a diary. The primary end point was complete response (no emesis and no rescue therapy) on days 1 to 5 postcisplatin, analyzed by a modified intent-to-treat approach. Treatment comparisons were made using logistic regression models. Tolerability was assessed by reported adverse events and physical and laboratory assessments. Results: The percentage of patients with complete response on days 1 to 5 was significantly higher in the aprepitant group (72.7% [n = 260] v 52.3% in the standard therapy group [n = 260]), as were the percentages on day 1, and especially on days 2 to 5 (P < .001 for all three comparisons). Conclusion: Compared with standard dual therapy, addition of aprepitant was generally well tolerated and provided consistently superior protection against CINV in patients receiving highly emetogenic cisplatin-based chemotherapy.

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