Melphalan-Prednisone-Thalidomide (MP-T) Demonstrates a Significant Survival Advantage in Elderly Patients ≥75 Years with Multiple Myeloma Compared with Melphalan-Prednisone (MP) in a Randomized, Double-Blind, Placebo-Controlled Trial, IFM 01/01.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 75-75 ◽  
Author(s):  
Cyrille Hulin ◽  
Thierry Facon ◽  
Philippe Rodon ◽  
Brigitte Pegourie ◽  
Lotfi Benboubker ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Partial Response ◽  
Elderly Patients ◽  
Controlled Trial ◽  
Response To Treatment ◽  
Rank Test ◽  
Newly Diagnosed ◽  
Very Elderly ◽  
Double Blind ◽  
Vte Prophylaxis

Abstract Background: The MP-T combination has become the standard treatment for newly diagnosed MM patients (pts) aged 65 to 75 years (Facon et al; Lancet 2007 [Epub ahead of print]). However, no specific therapeutic recommendation exists for pts ≥75 years regarding the benefit of adding thalidomide to MP. Patients older than 75 years have frequently been excluded from large clinical trials, although they represent more than 20% of MM pts. Methods: The IFM 01-01 trial was initiated in 4/2002. Pts ≥75 years with untreated MM were randomized to receive MP-placebo (M [0.2mg/kg/d] + P [2 mg/kg/d day1–4]) x 12 courses every 6-weeks + placebo) or MP-T (MP + daily thalidomide [100mg/d]). No anti-VTE prophylaxis was given. The primary end-point was overall survival (OS). Secondary end points were progression-free survival (PFS), response to treatment, and toxicity. Trial enrollment was prospectively planned for 258 patients. Two interim analyses were performed after inclusion of 150 and 200 patients. The IFM board decided to stop enrollment after the second interim analysis. Results: In all, 232 pts were randomized and 3 failed to meet inclusion criteria. In all, 229 pts were analyzed (113 MP-T; 116 MP-placebo) with a median age of 78.5 years (36% ≥80years). No differences between the 2 groups for baseline characteristics were observed except for gender (p=0.03). Data were analysed on an intent-to-treat basis. The median follow-up time was 24 months. The median OS time (se) was 45.3 (1.6) months with MP-T vs 27.7 (2.1) months with MP-placebo, the benefit was significant (p=0.03 log-rank test). The median PFS time (se) was 24.1 (2) months with MP-T vs 19 (1.4) months with MP-placebo (p=0.001). Rates of at least partial response, very good partial response and complete response were 62%, 22% and 7% with MP-T vs 31%, 7% and 1% with MP-placebo, respectively (p<0.001). In the MP-T arm, 42% of pts stopped treatment due to toxicity vs 11% in the MP-placebo arm. The major reasons in the MP-T arm were peripheral neuropathy (12/48), neutropenia (7/48), and DVT (7/48). Some toxicities (Grade 2–4) were significantly increased with MP-T: peripheral neuropathy (20% vs 5%), neutropenia (23% vs 9%) depression (7% vs 2%). There were no significative differences in DVT rates for MP-T (6%) vs MP-placebo (4%) or somnolence (6% vs 3%, respectively). After relapse in the MP-placebo arm, 77% of patients received Thalidomide. Survival time after progression was similar in the 2 groups, 9.8 months after MP-placebo and 9.3 months after MP-T. Conclusion: These results confirm the superiority of MP-T over MP for prolonging OS in elderly patients with newly diagnosed MM. The toxicity was acceptable in this very elderly population ≥ 75 years. A new era of progress is opened for these very elderly patients.

Comparison of melphalan-prednisone-thalidomide (MP-T) to melphalan-prednisone (MP) in patients 75 years of age or older with untreated multiple myeloma (MM). Preliminary results of the randomized, double-blind, placebo controlled IFM 01–01 trial

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8001-8001 ◽  
Author(s):  
C. Hulin ◽  
J. Virion ◽  
X. Leleu ◽  
P. Rodon ◽  
B. Pegourie ◽  
...  
Keyword(s):  
Partial Response ◽  
Progression Free Survival ◽  
Data Safety Monitoring Board ◽  
Response To Treatment ◽  
Rank Test ◽  
Double Blind ◽  
Vte Prophylaxis ◽  
Preliminary Results ◽  
Intent To Treat ◽  
Therapeutic Recommendation

8001 Background: The MP-T combination has been shown to be the standard treatment in newly diagnosed MM patients (pts) aged 65 to 75 years (Facon et al; JCO 2006; 24, A1). However, no specific therapeutic recommendation exists for pts older than 75 years regarding the benefit of adding Thalidomide to MP. Methods: The IFM 01–01 trial was initiated in 04/2002. Patients > 75 years with untreated MM were randomized to receive MP (Melphalan 0.2mg/kg/d + Prednisone 2 mg/kg/d day1–4, 12 courses at 6-weeks intervals) + placebo (MP-placebo) vs MP + daily Thalidomide 100mg/d (MP-T). No anti-VTE prophylaxis was given. The primary end-point was overall survival (OS). Secondary end points were progression-free survival (PFS), response to treatment and toxicity. A first interim analysis was performed after the inclusion of 150 patients and a data safety monitoring board recommended a second analysis after the accrual of 200 patients. We here present the preliminary results of this analysis. Results: At the reference date of November 1, 2006, 232 pts were randomised. In all, 200 pts were analysed (100 per group), with 33.5% of pts >80 years (median age, 78.4 years). There were no differences between the 2 groups regarding baseline characteristics. Data were analysed on an intent-to-treat basis. After the completion of therapy the rates of partial response and very good partial response were 31% and 8% respectively with MP-placebo vs 61% and 22% respectively with MP-T. The median PFS time was 19 months (95%-CI 14.6–21.5) with MP-placebo vs 24.1 months (95%-CI 19.4–29.7) with MP-T (p=0.004 log-rank test). In the MP-T arm, 43/100 pts stopped treatment due to toxicity (10 due to neuropathy) versus 11/100 in the MP-placebo arm. Toxicity (Grade 2–4) included peripheral neuropathy (18%), somnolence (7%) and DVT (7%) with MP-T, vs 6%, 6% and 1% respectively, with MP-placebo. Final results including OS data will be presented at the meeting. Conclusion: MPT is an effective combination with acceptable toxicity in patients with MM = 75 years of age, with a significant improvement in PFS. No significant financial relationships to disclose.

Double-blind controlled trial of azathioprine in children with newly diagnosed type I diabetes

Diabetes ◽  
1989 ◽  
Vol 38 (6) ◽  
pp. 779-783 ◽  
Author(s):  
J. J. Cook ◽  
I. Hudson ◽  
L. C. Harrison ◽  
B. Dean ◽  
P. G. Colman ◽  
...  
Keyword(s):  
Type I Diabetes ◽  
Controlled Trial ◽  
Type I ◽  
Newly Diagnosed ◽  
Double Blind

scholarly journals Methotrimeprazine versus haloperidol in palliative care patients with cancer-related nausea: a randomised, double-blind controlled trial

BMJ Open ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. e029942 ◽  
Author(s):  
Janet Rea Hardy ◽  
Helen Skerman ◽  
Jennifer Philip ◽  
Phillip Good ◽  
David C Currow ◽  
...  
Keyword(s):  
Palliative Care ◽  
Outcome Measures ◽  
Controlled Trial ◽  
Response Rates ◽  
Complete Response ◽  
Response To Treatment ◽  
Secondary Outcome ◽  
Double Blind ◽  
Intention To Treat ◽  
Point Reduction

ObjectivesMethotrimeprazine is commonly used for the management of nausea but never tested formally against other drugs used in this setting. The aim was to demonstrate superior antiemetic efficacy.DesignDouble-blind, randomised, controlled trial of methotrimeprazine versus haloperidol.Setting11 palliative care sites in Australia.ParticipantsParticipants were >18 years, had cancer, an average nausea score of ≥3/10 and able to tolerate oral medications. Ineligible patients had acute nausea related to treatment, nausea for which a specific antiemetic was indicated, were about to undergo a procedure or had received either of the study drugs or a change in glucocorticoid dose within the previous 48 hours.InterventionsBased on previous studies, haloperidol was used as the control. Participants were randomised to encapsulated methotrimeprazine 6·25 mg or haloperidol 1·5 mg one time or two times per day and assessed every 24 hours for 72 hours.Main outcome measuresA ≥two-point reduction in nausea score at 72 hours from baseline. Secondary outcome measures were as follows: complete response at 72 hours (end nausea score less than 3), response at 24 and 48 hours, vomiting episodes, use of rescue antiemetics, harms and global impression of change.ResultsResponse to treatment at 72 hours was 75% (44/59) in the haloperidol (H) arm and 63% (36/57) in the methotrimeprazine (M) arm with no difference between groups (intention-to-treat analysis). Complete response rates were 56% (H) and 51% (M). In theper protocolanalysis, there was no difference in response rates: (85% (44/52) (H) and 74% (36/49) (M). Completeper protocolresponse rates were 64% (H) and 59% (M). Toxicity worse than baseline was minimal with a trend towards greater sedation in the methotrimeprazine arm.ConclusionThis study did not demonstrate any difference in response rate between methotrimeprazine and haloperidol in the control of nausea.Trial registration numberACTRN 12615000177550.

Using Activities of Daily Living Assessments to Measure the Effectiveness of Vitamin D Supplements in Elderly Long-Stay Patients

1987 ◽  
Vol 50 (2) ◽  
pp. 60-62 ◽  
Author(s):  
D Corless ◽  
M Ellis ◽  
E Dawson ◽  
F Fraser ◽  
S Evans ◽  
...  
Keyword(s):  
Vitamin D ◽  
Elderly Patients ◽  
Activities Of Daily Living ◽  
Daily Living ◽  
Controlled Trial ◽  
Double Blind ◽  
Hydroxyvitamin D ◽  
Low Concentrations ◽  
25 Hydroxyvitamin D ◽  
Vitamin D Supplements

Selected activities of daily living were used to measure improvement in independence of long-stay elderly patients known to have low concentrations of plasma 25-hydroxyvitamin D. This was a double-blind random controlled trial lasting between 8 and 40 weeks. No significant changes were found in either group.

scholarly journals Age is not the only risk factor in COVID-19: the role of comorbidities and of long staying in residential care homes

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
M. D’ascanio ◽  
M. Innammorato ◽  
L. Pasquariello ◽  
D. Pizzirusso ◽  
G. Guerrieri ◽  
...  
Keyword(s):  
Mortality Rate ◽  
Elderly Patients ◽  
Clinical Outcomes ◽  
Residential Care ◽  
Pneumonia Severity Index ◽  
Care Homes ◽  
Categorical Variables ◽  
Rank Test ◽  
Very Elderly ◽  
Arterial Blood

Abstract Background The actual SARS-CoV-2 outbreak caused a highly transmissible disease with a tremendous impact on elderly people. So far, few studies focused on very elderly patients (over 80 years old). In this study we examined the clinical presentation and the outcome of the disease in this group of patients, admitted to our Hospital in Rome. Methods This is a single-center, retrospective study performed in the Sant’Andrea University Hospital of Rome. We included patients older than 65 years of age with a diagnosis of COVID-19, from March 2020 to May 2020, divided in two groups according to their age (Elderly: 65–80 years old; Very Elderly > 80 years old). Data extracted from the each patient record included age, sex, comorbidities, symptoms at onset, the Pneumonia Severity Index (PSI), the ratio of the partial pressure of oxygen in arterial blood (PaO2) to the inspired oxygen fraction (FiO2) (P/F) on admission, laboratory tests, radiological findings on computer tomography (CT), length of hospital stay (LOS), mortality rate and the viral shedding. The differences between the two groups were analyzed by the Fisher’s exact test or the Wilcoxon signed-rank test for categorical variables and the Mann-Whitney U test for continuous variables. To assess significance among multiple groups of factors, we used the Bonferroni correction. The survival time was estimated by Kaplan-Meier method and Log Rank Test. Univariate and Multivariate logistic regression were performed to estimate associations between age, comorbidities, provenance from long-stay residential care homes (LSRCH) s and clinical outcomes. Results We found that Very Elderly patients had an increased mortality rate, also due to the frequent occurrence of multiple comorbidities. Moreover, we found that patients coming from LSRCHs appeared to be highly susceptible and vulnerable to develop severe manifestations of the disease. Conclusion We demonstrate that there were considerable differences between Elderly and Very Elderly patients in terms of inflammatory activity, severity of disease, adverse clinical outcomes. To establish a correct risk stratification, comorbidities and information about provenience from LSRCHs should be considered.

Using Mixture of Normal Distributions to Detect Treatment Effects when the Frequentist Method Fails

2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Anthony Orlando
Keyword(s):  
Dose Response ◽  
Linear Models ◽  
Controlled Trial ◽  
Response To Treatment ◽  
Double Blind ◽  
Underlying Assumption ◽  
Normal Distributions ◽  
Efficacy Measure ◽  
Baseline Weight ◽  
Mixture Of Normal Distributions

Background: Results from a clinical trial can either support the efficacy and safety of a new compound or fail to provide such evidence. One reason for ‘non[1]positive’ result is due to the underlying assumption of normality and homogeneity of variances, which are quite often violated when analyzing data from clinical trials, despite randomization. A question of interest is can we obtain more informative results when using mixture of normal distributions or linear models (MLMs) in such cases. Introduction: MLM can be used when traditional methods fail. MLMs “search” within the variability in data to identify components or subgroups of individuals (also known as latent classes) who have common intercepts and common slopes of change in a variable/endpoint of interest but whose intercepts and slopes are different from other subsets of patients. Thus, MLMs can be used to identify subgroups of patients exhibiting differential response to treatment within each treatment arm. The purpose of our study was to examine the usefulness of using MLM in such circumstances. Methods: Data of 155 subjects taken from a Multicenter, randomized, double blind, placebo controlled trial that evaluated the efficacy of Cpn10, administered twice weekly subcutaneously to treat Rheumatoid Arthritis was taken to evaluate the usefulness of MLM. The primary efficacy measure ACR20 was analyzed using a 3-step process: first, MLM was used to estimate RA duration using a 3-component model. The second step took the results of the first step to inform the logistic model and its analyses. Model was fitted with an intercept, MLM components, treatment arm, RA duration (linear and quadratic), dose response (modeled as an interaction effect), age and baseline weight. LOCF was used to impute for missing data. Data was analyzed using MLM and SAS v 9.0. Results: The model was a good fit to the data with a likelihood ratio significant at p=0.026, and a significant increase in the -2log L. We also observed low p-values for those variables that were non normal. Overall and for the 75 mg dose, Cpn 10 was efficacious relative to placebo, p<0.050. We also observed that dose response was significant at p><0.15 Conclusion: The use of MLM adds value because it can be used to understand the disease experience or the value of treatment when traditional statistical methods cannot. Key words: Mixture of linear models, normality, entropy.

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