Impact of age on the efficacy and safety of extended-duration thromboprophylaxis in medical patients

2013 ◽  
Vol 110 (12) ◽  
pp. 1152-1163 ◽  
Author(s):  
Russell D. Hull ◽  
Sebastian M. Schellong ◽  
Victor F. Tapson ◽  
Manuel Monreal ◽  
Meyer-Michel Samama ◽  
...  
Keyword(s):  
Bleeding Risk ◽  
Absolute Difference ◽  
Medical Patients ◽  
Open Label ◽  
Double Blind ◽  
Vein Thrombosis ◽  
Extended Duration ◽  
Post Hoc ◽  
Reduced Mobility ◽  
The Impact

SummaryThe EXCLAIM study enrolled hospitalised acutely ill medical patients with age >40 years and recently-reduced mobility into a trial of extended-duration anticoagulant thromboprophylaxis. This post-hoc analysis evaluated the impact of age on patient outcomes. After completion of open-label therapy with enoxaparin 40 mg once-daily (10 ± 4 days), eligible patients underwent randomisation to receive double-blind therapy of enoxaparin (n=2,975) or placebo (n=2,988) for 28 ± 4 days. During follow-up, the venous thromboembolism (VTE) risk increased with age in both treatment groups. In patients with age >75 years, those who received extended-duration enoxaparin had lower incidence of VTE (2.5% vs 6.7%; absolute difference [AD] [95% confidence interval]: −4.2% [−6.5, −2.0]), proximal deep-vein thrombosis (2.5% vs 6.6%; AD −4.1 % [−6.2, −2.0]), and symptomatic VTE (0.3% vs 1.5%; AD −1.2% [−2.2, −0.3]), in comparison to those who received placebo. In patients with age ≤75 years, those who received enoxaparin had reduced VTE (2.4% vs 2.8%; AD −0.4% [−1.5, 0.7]) and symptomatic VTE (0.2% vs 0.7%; AD −0.6% [−1.0, −0.1]) in comparison to those who received placebo. In both age subgroups, patients who received enoxaparin had increased rates of major bleeding versus those who received placebo: age >75 years (0.6% vs 0.2%; AD +0.3% [−0.2, 0.9], respectively); age ≤75 years (0.7% vs 0.2%; AD +0.5% [0.1, 0.9]). Patients in both age subgroups that received enoxaparin had similar low bleeding rates (0.6% and 0.7%, respectively). VTE risk increased with age, though the bleeding risk did not. Patients with age >75 years had a more favourable benefit-to-harm profile than younger patients.

Extended-Duration Enoxaparin for Venous Thromboembolism Prophylaxis in Acutely Ill Medical Patients: An Evaluation of the EXCLAIM Study Based on a Recently Recommended Composite Efficacy Endpoint.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1870-1870 ◽  
Author(s):  
Sebastian M. Schellong ◽  
Russell D. Hull ◽  
Victor F. Tapson ◽  
Manuel Monreal ◽  
Meyer-Michel Samama ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Composite Endpoint ◽  
Medical Patients ◽  
Double Blind ◽  
Once Daily ◽  
All Cause Mortality ◽  
Standard Duration ◽  
Extended Duration ◽  
Level 1 ◽  
Reduced Mobility

Abstract Introduction The EXCLAIM study has shown that in acutely ill medical patients who have received a standard 10-day period of prophylaxis with enoxaparin, extended-duration prophylaxis with enoxaparin for 4 weeks reduces the relative risk of the primary composite endpoint of asymptomatic proximal deep-vein thrombosis (DVT), symptomatic DVT or pulmonary embolism (PE), and fatal PE by 44% compared with placebo (2.8% vs 4.9%; RR 0.56; 95% CI 0.39–0.80; p=0.0011). We assessed the consistency of these results using the composite efficacy endpoint recently proposed for venous thromboembolism (VTE) prophylaxis studies by the European Committee for Medicinal Products for Human Use (CHMP) which, in addition, takes all-cause mortality into account. Methods Patients enrolled in the EXCLAIM study had a recent reduced mobility (≤3 days) due to a medical illness, were aged 40 years or older, and had anticipated level 1 (total bed rest or sedentary without bathroom privileges) or level 2 (level 1 with bathroom privileges) reduced mobility with further risk factors. Eligible patients received enoxaparin 40mg SC once-daily for 10±4 days. Patients were then double-blind randomized and received either enoxaparin 40mg SC once-daily or placebo for a further 28±4 days. Asymptomatic DVT were diagnosed by bilateral compression ultrasound after completion of the randomized treatment period. Suspected cases of symptomatic DVT or PE were confirmed by objective tests. Fatal PE were confirmed by autopsy where possible. Data were analyzed using the CHMP-recommended composite efficacy endpoint of proximal DVT, adjudicated PE and all-cause mortality. Results Eligible patients enrolled at 370 sites in 20 countries received standard-duration prophylaxis with enoxaparin. Of these, 4114 patients were double-blind randomized and 4040 received extended-duration prophylaxis with enoxaparin (n=2013) and placebo (n=2027), respectively. Extended-duration enoxaparin reduced the relative risk of the CHMP composite endpoint by 26% compared with placebo (5.8% vs 7.9%; RR 0.74; 95% CI 0.58–0.95; p=0.018). Conclusion The significant reduction in the incidence of the primary efficacy endpoint associated with the use of extended-duration enoxaparin compared with placebo, following standard duration enoxaparin, was consistent when applying both the pre-defined EXCLAIM and the CHMP-recommended composite endpoints, the latter of which included all-cause mortality in addition to proximal DVT and adjudicated PE.

Abstract 2115: Results of CONTROL, a Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Study of the Effects of Tetrahydrobiopterin on Blood Pressure in Subjects with Poorly Controlled Hypertension

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Arshed Quyyumi ◽  
Susan Zieman ◽  
Emil Kakkis ◽  
John Hopkins ◽  
Martha Nicholson
Keyword(s):  
Blood Pressure ◽  
Antihypertensive Drugs ◽  
Statistical Significance ◽  
No Production ◽  
Parallel Study ◽  
Open Label ◽  
Double Blind ◽  
Lower Blood ◽  
Markers Of Oxidative Stress ◽  
Post Hoc

BACKGROUND: Tetrahydrobiopterin (6R-BH4) is a cofactor for nitric oxide (NO) synthesis. Reduced BH4 bioavailability uncouples NO synthase, decreases NO production, increases superoxide production, and may contribute to hypertension. 6R-BH4 administration has been shown to lower blood pressure (BP) and improve endothelial function in animal models and in two small, open-label clinical studies. A randomized, placebo-controlled, multicenter, parallel study was designed (‘CONTROL’) to evaluate the antihypertensive effects of 6R-BH4 in patients with treated, but poorly controlled, hypertension. METHODS: A total of 116 subjects with hypertension (SBP/DBP> 135/85) despite a stable regimen of at least two antihypertensive drugs were randomized 2:1 to oral 6R-BH4 (n=77) or placebo (n=39) and stratified by presence or absence of type 2 diabetes. Subjects received a daily dose of 10 mg/kg 6R-BH4 for 8 weeks. Endpoints were change from baseline in SBP and DBP over 8 weeks of treatment. Other measures of efficacy included change in insulin sensitivity, proteinuria, and biochemical markers of oxidative stress and NO production. RESULTS: 6R-BH4-treated subjects had a 4.4-mm Hg drop in SBP (baseline mean, 145 mm Hg) compared with a 6.4-mm Hg drop in placebo-treated subjects (baseline mean, 143 mm Hg; p=0.428). 6R-BH4-treated subjects had a 5.0-mm Hg drop in DBP (baseline mean, 90 mm Hg) compared with a 4.8-mm Hg drop in placebo-treated subjects (baseline mean, 93 mm Hg; p=0.907). No statistically significant differences in either endpoint were seen in subgroup analyses of subjects with or without diabetes, or in other measures of efficacy or safety. Post-hoc analyses in subjects with higher SBP at baseline (>150 mm Hg) showed a better SBP response to 6R-BH4 (−14.1 mm Hg) than to placebo (−5.9 mm Hg) however too few subjects with higher SBP were enrolled to reach statistical significance (6R-BH4, n=19; placebo, n=7: p=0.149). CONCLUSIONS: Oral 6R-BH4 at a dose of 10 mg/kg/day showed no anti-hypertensive effect in subjects already on a stable regimen of at least two antihypertensive drugs.

Analysis of the effect of crossover from placebo (PBO) to darolutamide (DARO) on overall survival (OS) benefit in the ARAMIS Trial.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 240-240
Author(s):  
Neal D. Shore ◽  
Karim Fizazi ◽  
Teuvo Tammela ◽  
Murilo Luz ◽  
Manuel Philco Salas ◽  
...  
Keyword(s):  
Treatment Effect ◽  
Safety Profile ◽  
Final Analysis ◽  
Phase Iii ◽  
Sensitivity Analyses ◽  
Primary Analysis ◽  
Open Label ◽  
Double Blind ◽  
Secondary Endpoints ◽  
The Impact

240 Background: DARO is a structurally distinct androgen receptor inhibitor approved for the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC) based on significantly prolonged metastasis-free survival compared with PBO (median 40.4 vs 18.4 months; hazard ratio [HR] 0.41; 95% confidence interval [CI] 0.34–0.50; P < 0.0001) and a favorable safety profile in the phase III ARAMIS trial. Following unblinding at the primary analysis, crossover from PBO to DARO was permitted for the subsequent open-label treatment phase. Sensitivity analyses were performed to assess the effect of PBO–DARO crossover on OS benefit. Methods: Patients (pts) with nmCRPC receiving androgen deprivation therapy were randomized 2:1 to DARO (n = 955) or PBO (n = 554). In addition to OS, secondary endpoints included times to pain progression, first cytotoxic chemotherapy, first symptomatic skeletal event, and safety. The OS analysis was planned to occur after approximately 240 deaths, and secondary endpoints were evaluated in a hierarchical order. Iterative parameter estimation (IPE) and rank-preserving structural failure time (RPSFT) analyses were performed as pre-planned sensitivity analyses to adjust for the treatment effect of PBO–DARO crossover. The IPE method used a parametric model for the survival times and iteratively determined the model parameter describing the magnitude of the treatment effect, whereas a grid search and non-parametric log-rank test were used for the RPSFT analysis. The IPE and RPSFT analyses both generated a Kaplan–Meier curve for the PBO arm that predicts what would have been observed in the absence of PBO–DARO crossover. Results: After unblinding, 170 pts (30.7% of those randomized to PBO) crossed over from PBO to DARO; median treatment duration from unblinding to the final data cut-off was 11 months. Final analysis of the combined double-blind and open label periods was conducted after 254 deaths (15.5% of DARO and 19.1% of PBO pts) and showed a statistically significant OS benefit for DARO vs PBO (HR 0.69; 95% CI 0.53–0.88; P = 0.003). Results from the IPE (HR 0.66; 95% CI 0.51–0.84; P < 0.001) and RPSFT (HR 0.68; 95% CI 0.51–0.90; P = 0.007) analyses were similar to those from the intention-to-treat population, showing that the impact of PBO–DARO crossover was small. Additional analyses accounting for the effect of PBO–DARO crossover will be presented. The safety profile of DARO continued to be favorable at the final analysis, and discontinuation rates at the end of the double-blind period remained unchanged from the primary analysis (8.9% with DARO and 8.7% with PBO). Conclusions: Early treatment with DARO in men with nmCRPC is associated with significant improvement in OS regardless of pts crossing over from PBO to DARO. The safety profile of DARO remained favorable at the final analysis. Clinical trial information: NCT02200614.

Effects of repetitive paired associative stimulation on brain plasticity and working memory in Alzheimer’s disease: a pilot randomized double-blind-controlled trial

2020 ◽  
pp. 1-13
Author(s):  
Sanjeev Kumar ◽  
Reza Zomorrodi ◽  
Zaid Ghazala ◽  
Michelle S. Goodman ◽  
Daniel M. Blumberger ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Working Memory ◽  
Brain Plasticity ◽  
Controlled Trial ◽  
Memory Performance ◽  
Double Blind ◽  
Paired Associative Stimulation ◽  
Post Hoc ◽  
The Impact

ABSTRACT Design: Pilot randomized double-blind-controlled trial of repetitive paired associative stimulation (rPAS), a paradigm that combines transcranial magnetic stimulation (TMS) of the dorsolateral prefrontal cortex (DLPFC) with peripheral median nerve stimulation. Objectives: To study the impact of rPAS on DLPFC plasticity and working memory performance in Alzheimer’s disease (AD). Methods: Thirty-two patients with AD (females = 16), mean (SD) age = 76.4 (6.3) years were randomized 1:1 to receive a 2-week (5 days/week) course of active or control rPAS. DLPFC plasticity was assessed using single session PAS combined with electroencephalography (EEG) at baseline and on days 1, 7, and 14 post-rPAS. Working memory and theta–gamma coupling were assessed at the same time points using the N-back task and EEG. Results: There were no significant differences between the active and control rPAS groups on DLPFC plasticity or working memory performance after the rPAS intervention. There were significant main effects of time on DLPFC plasticity, working memory, and theta–gamma coupling, only for the active rPAS group. Further, on post hoc within-group analyses done to generate hypotheses for future research, as compared to baseline, only the rPAS group improved on post-rPAS day 1 on all three indices. Finally, there was a positive correlation between working memory performance and theta–gamma coupling. Conclusions: This study did not show a beneficial effect of rPAS for DLPFC plasticity or working memory in AD. However, post hoc analyses showed promising results favoring rPAS and supporting further research on this topic. (Clinicaltrials.gov-NCT01847586)

scholarly journals Biomarker Research in ADHD: the Impact of Nutrition (BRAIN) - study protocol of an open-label trial to investigate the mechanisms underlying the effects of a few-foods diet on ADHD symptoms in children

BMJ Open ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. e029422 ◽  
Author(s):  
Tim Stobernack ◽  
Stefan P W de Vries ◽  
Rob Rodrigues Pereira ◽  
Lidy M Pelsser ◽  
Cajo J F ter Braak ◽  
...  
Keyword(s):  
Well Being ◽  
Adhd Symptoms ◽  
Long Term Effects ◽  
Open Label ◽  
Double Blind ◽  
Adhd Treatment ◽  
Open Label Trial ◽  
Biomarker Research ◽  
The Impact ◽  
Brain Study

IntroductionAttention deficit hyperactivity disorder (ADHD) is the most common childhood behavioural disorder, causing significant impediment to a child’s development. It is a complex disorder with numerous contributing (epi)genetic and environmental factors. Currently, treatment consists of behavioural and pharmacological therapy. However, ADHD medication is associated with several side effects, and concerns about long-term effects and efficacy exist. Therefore, there is considerable interest in the development of alternative treatment options. Double-blind research investigating the effects of a few-foods diet (FFD) has demonstrated a significant decrease in ADHD symptoms following an FFD. However, an FFD requires a considerable effort of both child and parents, limiting its applicability as a general ADHD treatment. To make FFD intervention less challenging or potentially obsolete, we need to understand how, and in which children, an FFD affects ADHD behaviour and, consequently, the child’s well-being. We hypothesise that an FFD affects brain function, and that the nutritional impact on ADHD is effectuated by a complex interplay between the microbiota, gut and brain, that is, the microbiota–gut–brain axis.Methods and analysisThe Biomarker Research in ADHD: the Impact of Nutrition (BRAIN) study is an open-label trial with researchers blinded to changes in ADHD symptoms during sample processing and initial data analyses.Ethics and disseminationThe Medical Research and Ethics Committee of Wageningen University has approved this study (NL63851.081.17, application 17/24). Results will be disseminated through peer-reviewed journal publications, conference presentations, (social) media and the BRAIN study website. A summary of the findings will be provided to the participants.Trial registration numberNCT03440346.Study datesCollection of primary outcome data started in March 2018 and will be ongoing until 100 children have participated in the study. Sample data analysis will start after all samples have been collected.

Extended-duration thromboprophylaxis in acutely ill medical patients with recent reduced mobility: Methodology for the EXCLAIM study

2006 ◽  
Vol 22 (1) ◽  
pp. 31-38 ◽  
Author(s):  
Russell D. Hull ◽  
Sebastian M. Schellong ◽  
Victor F. Tapson ◽  
Manuel Monreal ◽  
Meyer-Michel Samama ◽  
...  
Keyword(s):  
Medical Patients ◽  
Extended Duration ◽  
Reduced Mobility

Consistent Venous Thromboembolism Risk Reduction by Extended- Versus Standard-Duration Enoxaparin Prophylaxis in Subgroups of Acutely Ill Medical Patients in the EXCLAIM Study.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1863-1863 ◽  
Author(s):  
Victor F. Tapson ◽  
Russell D. Hull ◽  
Sebastian M. Schellong ◽  
Manuel Monreal ◽  
Meyer-Michel Samama ◽  
...  
Keyword(s):  
Major Bleeding ◽  
Odds Ratio ◽  
Primary Diagnosis ◽  
Medical Patients ◽  
Once Daily ◽  
Standard Duration ◽  
Extended Duration ◽  
Level 1 ◽  
Reduced Mobility ◽  
Patient Subgroups

Abstract Introduction In the EXCLAIM study, extended-duration enoxaparin prophylaxis reduced the relative risk of VTE in acutely ill medical patients by 44% compared with placebo, following standard-duration prophylaxis (2.8% vs 4.9%; RR 0.56; 95% CI 0.39–0.80; p=0.0011). We assessed the benefits of extended-duration enoxaparin prophylaxis in subgroups of acutely ill medical patients with the most prominent primary diagnoses enrolled in EXCLAIM. Methods Patients enrolled in EXCLAIM had: recent reduced mobility (≤3 days) due to a medical illness, age ≥40 years, and anticipated level 1 (total bed rest or sedentary without bathroom privileges) or level 2 (level 1 with bathroom privileges) reduced mobility with further risk factors. Eligible patients received enoxaparin 40mg SC once-daily for 10±4 days, and were then double-blind randomized and received enoxaparin 40mg SC once-daily (n=2013) or placebo (n=2027) for a further 28±4 days. Asymptomatic DVT were diagnosed by bilateral compression ultrasound after completion of the randomized treatment. Suspected cases of symptomatic DVT or PE were confirmed by objective tests. Fatal PE were confirmed by autopsy where possible. Univariate logistic regressions were conducted to estimate treatment effects in patient subgroups. The primary safety endpoint was major bleeding. Results Baseline characteristics were similar between treatments within each primary diagnosis subgroup, and the considered primary diagnoses accounted for >80% of the enrolled population. The reduced VTE incidence associated with extended-duration enoxaparin prophylaxis was consistent across subgroups of patients with different primary diagnoses (Table). The incidence of major bleeding was generally higher in patients receiving extended-duration prophylaxis (Table). Table: VTE and major bleeding in patient subgroups receiving extended-duration vs standard-duration prophylaxis/placebo Primary diagnosis Incidence of VTE (%)* Odds Ratio [95% CI]** Incidence of Major Bleeding (%)*** Odds Ratio [95% CI] Extended Enox Standard Enox/Placebo Extended Enox Standard Enox/Placebo *N=3347 evaluable patients; **Alpha adjustment for an interim analysis; ***N=4040 treated patients Heart failure, NYHA class III or IV 3.1 4.7 0.64 [0.29–1.39] 0.0 0.2 N/A Acute respiratory insufficiency 2.2 3.7 0.60 [0.27–1.34] 0.6 0.2 3.15 [0.33–30.4] Post ischemic stroke 2.1 8.3 0.24 [0.06–0.91] 0.6 0.0 N/A Acute infection without septic shock 3.6 5.3 0.66 [0.36–1.22] 0.8 0.2 5.16 [0.60–44.3] Conclusion Extended enoxaparin prophylaxis consistently reduced VTE risk in acutely ill medical patients with the most prominent primary diagnoses compared with placebo following standard-duration prophylaxis. Major bleeding was generally higher in the extended-duration enoxaparin arm, but rates of bleeding were low. These findings are consistent with the primary findings of the EXCLAIM study which demonstrated the clinical benefit of the extended-duration enoxaparin regimen.

Prevalence of Risk Factors for VTE In Hospitalized Medical and Surgical Patients. Data From the Comparison of Methods for Thromboembolic Risk Assessment with Clinical Perceptions and AwareneSS In Real Life Surgical and Medical Patients (COMPASS) Study

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3337-3337
Author(s):  
Grigoris T Gerotziafas ◽  
Miltos Chrysanthidis ◽  
Reda Isaad ◽  
Hela Baccouche ◽  
Chrysoula Papageorgiou ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Assessment ◽  
Gastrointestinal Disease ◽  
Real Life ◽  
Bleeding Risk ◽  
Hospitalized Patients ◽  
Assessment Model ◽  
Surgical Patients ◽  
Medical Patients ◽  
The Impact

Abstract Abstract 3337 Introduction: Risk assessment models (RAM) are helpful tools for the screening VTE risk in hospitalized patients. Most of the available RAMs have been constructed on a disease-based or surgery-based approach and include some of the most relevant risk factors for VTE. There is limited information on the impact and importance of individual and comorbidity related risk factors for VTE present during hospitalization on the global VTE risk. Incorporation of the most frequent VTE risk and bleeding risk factors related to comorbidities might improve the ability of RAM to detect real-life patients at risk VTE and to evaluate drawbacks for the application of thromboprophylaxis. Aim of the study: The primary aim of the COMPASS programme was to evaluate the prevalence of the all known VTE and bleeding risk factors reported in the literature in real-life surgical and medical hospitalized patients. Methods: A prospective multicenter cross-sectional observational study was conducted in 6 hospitals in Greece and 1 in France. All inpatients aged >40 years hospitalised for medical diseases and inpatients aged >18 years admitted due to a surgical procedure and hospitalisation for a period exceeding three days were included. Patients and their treating physicians were interviewed with standardised questionnaire including all VTE and bleeding risk factors described in literature (130 items) on the third day of hospitalisation. Patients not giving informed consent, or receiving anticoagulant treatment for any reason or hospitalised in order to undergo diagnostic investigation without any further therapeutic intervention were excluded. Results: A total of 806 patients were enrolled in the study (414 medical and 392 surgical). Most frequent causes of hospitalisation in medical patients were infection (42%), ischemic stroke (14%), cancer (13%), gastrointestinal disease (9%), pulmonary disease (4%), renal disease (3%) and rheumatologic disease (1,4%). Surgical patients were hospitalised for vascular disease (22%) cancer (19,4%) gastrointestinal disease (12,5%), infection (8%), orthopaedic surgery and trauma (14%) or minor surgery (7%). Analysis of the frequency of risk factors for VTE showed that active cancer, recent hospitalisation, venous insufficiency and total bed rest without bathroom privileges were frequent in both groups. Medical patients had significantly more frequently than surgical patients several important predisposing risk factors for VTE. Moreover, medical patient had more frequently than surgical ones bleeding risk factors. The data for the most frequent risk factors are summarised in Table 1. Conclusion: COMPASS is the first registry that provides key data on the prevalence of all known VTE and bleeding risk factors in real life medical and surgical patients hospitalised in two countries of European Union. The analysis of the data shows that in addition to risk stemin from the disease or surgical act both medical and surgical patients share common VTE risk factors. The careful analysis of the most frequent and relevant VTE risk factors will allow the derivation of a practical VTE and bleeding risk assessment model taken into account these factors. Disclosures: Chrysanthidis: Sanofi-Aventis: Employment.

Efficacy variables in patients with cancer versus patients without cancer treated with methylnaltrexone or placebo: An analysis of two placebo-controlled studies.

2018 ◽  
Vol 36 (34_suppl) ◽  
pp. 1-1
Author(s):  
Bruce Chamberlain ◽  
Michelle Rhiner ◽  
Neal E Slatkin ◽  
Nancy Stambler ◽  
Robert Joseph Israel
Keyword(s):  
Opioid Use ◽  
Advanced Illness ◽  
Open Label ◽  
Double Blind ◽  
Patients With Cancer ◽  
Pooled Data ◽  
Bowel Movements ◽  
Open Label Extension ◽  
Post Hoc ◽  
Clinical Trial Information

1 Background: A post-hoc analysis of pooled data from two randomized, double-blind studies and their open-label extensions evaluated whether baseline characteristics and efficacy endpoints differ between cancer and noncancer adults with advanced illness and opioid-induced constipation treated with methylnaltrexone (MNTX) or placebo. Methods: Patients received SC MNTX 0.15 mg/kg or placebo (study 302) and SC MNTX 8 mg (38≤62 kg), 12 mg (≥62 kg), or placebo (study 4,000) every other day for two weeks and received the same doses of MNTX as needed during the first 2 weeks of the open-label extensions. Double-blind populations were stratified by those with/without cancer. Efficacy endpoints included rescue-free bowel movements (RFBMs) within 4 hours after each dose for ≥2 of the first 4 doses; time to rescue-free laxation; rescue laxatives use; and ≥3 RFBMs/week and ≥1 RFBM/week in ≥3 of 4 weeks. Results: Median baseline opioid use (mg/day) was greater in cancer (187.9 placebo [n=114]; 180.0 MNTX [n=116]) versus noncancer patients (80.0 placebo [n=71]; 120.0 MNTX [n=62]). MNTX significantly ( P<0.0001) improved the proportion of cancer (56.9%) and noncancer (58.1%) patients with an RFBM within 4 hours after each dose for ≥ two of the first four doses versus placebo (5.3% cancer; 11.3% noncancer). Median time to laxation was significantly ( P≤0.0002) shorter in cancer (0.96 hours) and noncancer (1.25 hours) patients 24 hours after the first dose of MNTX versus placebo (22.53 and >24 hours, respectively). Rescue laxatives were used by 39.7% of cancer and 30.6% of noncancer MNTX patients versus 51.8% of cancer and 39.4% of noncancer placebo patients. Of 108 open-label extension double-blind MNTX patients, 79 (73.1%) achieved ≥3 RFBMs/week with ≥1 RFBM/week increase in ≥ three of four weeks versus 48 (46.6%) of 103 double-blind placebo patients (data from double-blind and first two weeks of open-label). Conclusions: MNTX treatment improved the laxation response, with a faster onset of laxation in patients with and without cancer, and reduced the need for rescue laxatives vs placebo. Improvements over placebo continued into the first two weeks of the open-label extensions for MNTX-treated patients. Clinical trial information: NCT00672477, NCT00402038.

Sign in / Sign up

Export Citation Format

Share Document