Doxycycline Combined With Bortezomib-Cyclophosphamide-Dexamethasone Chemotherapy for Newly Diagnosed Cardiac Light-Chain Amyloidosis: A Multicenter Randomized Controlled Trial

Circulation ◽  
2021 ◽  
Author(s):  
Kai-ni Shen ◽  
Wei-jun Fu ◽  
Yu Wu ◽  
Yu-jun Dong ◽  
Zhong-xia Huang ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Light Chain ◽  
Controlled Trial ◽  
Hazard Ratio ◽  
Stage Ii ◽  
Control Group ◽  
Al Amyloidosis ◽  
Randomized Controlled ◽  
Multicenter Randomized Controlled Trial

Background: Doxycycline was demonstrated in a retrospective study to be associated with greater survival in patients with light chain (AL) amyloidosis. Therefore, we prospectively compared the efficacy of bortezomib-cyclophosphamide-dexamethasone (CyBorD) and CyBorD combined with doxycycline for cardiac AL amyloidosis. Methods: This was a multicenter, open-label randomized controlled trial. Patients with Mayo 2004 stage II-III AL amyloidosis were included. Patients were randomized to doxycycline 100 mg twice daily along with 9 cycles of CyBorD (doxycycline group) or to 9 cycles of CyBorD alone (control group). The primary outcome was 2-year progression-free survival (PFS). PFS was defined as the time from randomization to death, hematologic progression or organ progression (heart, kidney or liver). Hematologic progression was defined based on substantial increase in free light chain. Increase in either N-terminal pro B-type natriuretic peptide or cardiac troponin was the main criterion for defining cardiac progression. Cardiac PFS, defined as the time from randomization to cardiac progression or death, was compared between groups in an exploratory analysis. The corresponding treatment hazard ratio was estimated using a Cox regression model. Results: 140 patients underwent randomization, with 70 in each group. The median age was 61 (range, 33-78) years with a male: female ratio of 1.75:1. Stage II disease was present in 34 (48.6%) and 33 (47.1%) patients in the doxycycline and control groups, respectively. After a median follow-up duration of 24.4 months, 32/70 (45.7%) of patients in the doxycycline group and 30/70 (42.9%) of patients in the control group experienced progression. PFS was not significantly different between groups (hazard ratio 0.97, 95% CI, 0.59-1.60, p =0.91). Cardiac progression occurred in 29/70 (41.4%) of patients in the doxycycline group and 26/70 (37.1%) of patients in the control group. The death rates for both groups by the end of follow-up was the same, 25/70 (35.7%). There were no significant differences observed for either cardiac PFS (hazard ratio 0.91, 95% CI, 0.54-1.55, p =0.74) or overall survival (hazard ratio 1.04, 95% CI, 0.60-1.81, p =0.89). Conclusions: Our trial demonstrated that doxycycline combined with CyBorD failed to prolong PFS or cardiac PFS compared with CyBorD alone in cardiac AL amyloidosis. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT03401372.

scholarly journals Doxycycline Combined with Bortezomib-Cyclophosphamide-Dexamethasone Chemotherapy for Newly Diagnosed Patients with Mayo 2004 Stage II-III Light-Chain Amyloidosis: A Randomized Controlled Multicenter Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1870-1870
Author(s):  
Kaini Shen ◽  
Yujun Dong ◽  
Weijun Fu ◽  
Yu Wu ◽  
Zhongxia Huang ◽  
...  
Keyword(s):  
Light Chain ◽  
Stage Ii ◽  
Controlled Study ◽  
Control Group ◽  
Al Amyloidosis ◽  
Randomized Controlled ◽  
Hematological Response ◽  
Organ Response ◽  
To Receive

【Introduction 】There is ongoing unmet need for effective therapies in Mayo 2004 stage II-III amyloid light-chain (AL) amyloidosis patients, who undergo early death due to cardiac dysfunction. Lately, in vitro studies demonstrated that doxycycline could induce disruption of fibril formation in transgenic mouse model of AL amyloidosis. Matched case-control study of standard chemotherapy with or without doxycycline confirmed higher hematological response, cardiac responses and superior survival with doxycycline in AL patients. However, the possible advantage of doxycycline on lower early mortality and better long-term survival has not been evaluated in a randomized controlled clinical trial. We designed a randomized unblinded controlled study to investigate the efficacy and safety of co-administration of oral doxycycline with bortezomib-cyclophosphamide-dexamethasone (BCD) regimen in treatment-naïve AL amyloidosis patients with Mayo 2004 stage II-III disease. 【Methods 】The randomized unblinded controlled study took place in 12 hospitals in China. Eligible participants were adults with a confirmed diagnosis of AL amyloidosis, whose Mayo 2004 stage were II or III. Enrolled patients were randomly allocated to receive either doxycycline combined with BCD or BCD alone as initial treatment. We chose stratified blocked randomization (block size of 4) to ensure Mayo stage II and III were evenly distributed between doxycycline group and control group. For both two groups, patients will receive 1.3mg/m2of subcutaneous bortezomib and 40mg of oral or intravenous dexamethasone on days 1, 8, 15 and 22, and 300mg/m2oral or intravenous cyclophosphamide on days 1, 8 and 15 of a 35-day cycle. This process was repeated for 9 cycles. Doxycycline was given orally 100mg twice daily for the experimental group. The primary endpoint is progression-free survival. Secondary endpoints include overall survival, adverse events, hematological response, organ response and safety of treatment. This trial has been registered with ClinicalTrials.gov (number NCT03401372) and recruitment and follow-up are ongoing. We planned to enroll a total of 140 participants. 【Results 】Between April 21st, 2018 and June 30th, 2019, 111 patients were enrolled and randomly assigned to receive doxycycline plus BCD (n=56) or BCD alone (n=55) (Figure 1). The baseline characteristics were shown in Table 1. The median age was 61 (range, 41-78) years with a male: female ratio of 1.64:1. Mayo 2004 stage II disease was present in 28 patients in the control group and 29 patients in the doxycycline group. Mayo 2004 stage III disease was present in 27 patients in the control group and 27 patients in the doxycycline group. The median cTnI was 0.10 (range, 0-1.92) μg/L, NT-proBNP 3647 (range, 271-20507) pg/mL, and dFLC 205.30 (50.28-791.90) mg/L, with no significant difference between either group. Organ involvement included the heart (100%), kidney (61.3%), liver (14.4%), peripheral nerves (10.8%) and gastrointestinal tract (5.4%). The percentage of hepatic involvement and 24-hour urine protein were higher in the doxycycline group. The median duration of doxycycline was 5.9 months. Only one patient discontinued doxycycline due to toxicity (Grade 2 rash). Till now, the median follow-up time was 6.1 months and no patients were lost to follow-up. Fourteen patients have completed 9 cycles of chemotherapy. In total, 22 patients died and disease progression occurred in 3 patients. Two patients discontinued treatment due to withdrawal of consent and one of them proceeded to autologous stem cell transplantation. Three patients discontinued study drug owing to unacceptable diarrhea and received second-line treatment based on ixazomib or melphalan afterwards. The grade 3/4 adverse effects were developed in 8 patients (1 infection, 1 mucositis and 6 diarrhea) in the control group and 6 patients (1 infection, 1 arrhythmia, 1 kidney dysfunction and 3 diarrhea) in the doxycycline group. 【Conclusions 】Our data suggested that addition of doxycycline to standard bortezomib-based chemotherapy was an tolerable regimen for treating patients with AL amyloidosis. If this protocol could significantly improve survival and organ response needs to be confirmed with further follow-up. Disclosures No relevant conflicts of interest to declare.

scholarly journals Observation on Pain Release by Long-Round Needle Therapy in Knee Osteoarthritis Related with Meridian-Sinews Theory

2013 ◽  
Vol 2013 ◽  
pp. 1-4 ◽  
Author(s):  
Yuan-shi Liu ◽  
Li-gong Xue ◽  
Xiao-jian Ma ◽  
Chun-shan Liu
Keyword(s):  
Randomized Controlled Trial ◽  
Knee Osteoarthritis ◽  
Therapy Group ◽  
Controlled Trial ◽  
Control Group ◽  
Curative Effect ◽  
Randomized Controlled ◽  
Multicenter Randomized Controlled Trial ◽  
Therapy Sessions

To evaluate the effectiveness of long-round needle therapy for pain relief in patients with knee osteoarthritis, 192 patients were included in a multicenter, randomized, controlled trial. 97 patients were randomized to the long-round needle therapy group (EG), and 95 patients were randomized to the control group (CG). In EG, the long-round needle therapy was performed once every 7 days for 3 therapy sessions. Ibuprofen sustained-release capsules were administered orally in CG, 1 pill each time, twice daily for 3 weeks. Curative effect was measured after the therapy and was evaluated at a 3-month follow-up interview. In EG, the treatment resulted in a basic cure for 79 patients, was effective for 15 patients, and was ineffective for 1 patient. In CG, the treatment resulted in a basic cure for 30 patients, was effective for 38 patients, and was ineffective for 21 patients. In the follow-up examination in EG, 75 patients were basically cured, and the treatment was effective for 11 patients and ineffective for 9. In CG, 22 were basically cured, 31 found the treatment effective, and 36 found the treatment ineffective. The curative effects in EG after both the treatment and the 3-mouth followup were significantly more superior than that in CG (P<0.01) which should be adopted more widely.

scholarly journals Effect of physician prescribed information on hospital readmission and death after discharge among patients with health failure: A randomized controlled trial

2021 ◽  
Vol 27 (1) ◽  
pp. 146045822199640
Author(s):  
Faranak Kazemi Majd ◽  
Vahideh Zarea Gavgani ◽  
Ali Golmohammadi ◽  
Ali Jafari-Khounigh
Keyword(s):  
Randomized Controlled Trial ◽  
Hospital Readmission ◽  
Medical Information ◽  
Controlled Trial ◽  
Intervention Group ◽  
Control Group ◽  
Randomized Controlled ◽  
Long Term Follow Up ◽  
Oral Information

In order to understand if a physician prescribed medical information changes, the number of hospital readmission, and death among the heart failure patients. A 12-month randomized controlled trial was conducted (December 2013–2014). Totally, 120 patients were randomly allocated into two groups of intervention ( n = 60) and control ( n = 60). Accordingly, the control group was given the routine oral information by the nurse or physician, and the intervention group received the Information Prescription (IP) prescribed by the physician as well as the routine oral information. The data was collected via telephone interviews with the follow-up intervals of 6 and 12 months, and also for 1 year after the discharge. The patients with the median age of (IQR) 69.5 years old (19.8) death upon adjusting a Cox survival model, [RR = 0.67, 95%CI: 0.46–0.97]. Few patients died during 1 year in the intervention group compared to the controls (7 vs 15) [RR = 0.47, 95%CI: 0.20–1.06]. During a period of 6-month follow-up there was not statistically significant on death and readmission between two groups. Physician prescribed information was clinically and statistically effective on the reduction of death and hospital readmission rates among the HF patients in long term follow-up.

scholarly journals Effectiveness of a psychological online training to promote physical activity among students: protocol of a randomized-controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Lena Violetta Krämer ◽  
Nadine Eschrig ◽  
Lena Keinhorst ◽  
Luisa Schöchlin ◽  
Lisa Stephan ◽  
...  
Keyword(s):  
Physical Activity ◽  
Randomized Controlled Trial ◽  
Mixed Model ◽  
Controlled Trial ◽  
Control Group ◽  
Web Based ◽  
Intention To Treat ◽  
Randomized Controlled ◽  
Link Type

Abstract Background Many students in Germany do not meet recommended amounts of physical activity. In order to promote physical activity in students, web-based interventions are increasingly implemented. Yet, data on effectiveness of web-based interventions in university students is low. Our study aims at investigating a web-based intervention for students. The intervention is based on the Health Action Process Approach (HAPA), which discriminates between processes of intention formation (motivational processes) and processes of intention implementation (volitional processes). Primary outcome is change in physical activity; secondary outcomes are motivational and volitional variables as proposed by the HAPA as well as quality of life and depressive symptoms. Methods A two-armed randomized controlled trial (RCT) of parallel design is conducted. Participants are recruited via the internet platform StudiCare (www.studicare.com). After the baseline assessment (t1), participants are randomized to either intervention group (immediate access to web-based intervention) or control group (access only after follow-up assessment). Four weeks later, post-assessment (t2) is performed in both groups followed by a follow-up assessment (t3) 3 months later. Assessments take place online. Main outcome analyses will follow an intention-to-treat principle by including all randomized participants into the analyses. Outcomes will be analysed using a linear mixed model, assuming data are missing at random. The mixed model will include group, time, and the interaction of group and time as fixed effects and participant and university as random effect. Discussion This study is a high-quality RCT with three assessment points and intention-to-treat analysis meeting the state-of-the-art of effectiveness studies. Recruitment covers almost 20 universities in three countries, leading to high external validity. The results of this study will be of great relevance for student health campaigns, as they reflect the effectiveness of self-help interventions for young adults with regard to behaviour change as well as motivational and volitional determinants. From a lifespan perspective, it is important to help students find their way into regular physical activity. Trial registration The German clinical trials register (DRKS) DRKS00016889. Registered on 28 February 2019

Challenges of Increasing Childcare Center Compliance With Nutrition Guidelines: A Randomized Controlled Trial of an Intervention Providing Training, Written Menu Feedback, and Printed Resources

2018 ◽  
Vol 33 (3) ◽  
pp. 399-411 ◽  
Author(s):  
Meghan Finch ◽  
Kirsty Seward ◽  
Taya Wedesweiler ◽  
Fiona Stacey ◽  
Alice Grady ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Group Intervention ◽  
Controlled Trial ◽  
Theoretical Domains Framework ◽  
Practice Change ◽  
Control Group ◽  
Food Groups ◽  
Randomized Controlled ◽  
Nutrition Guidelines

Purpose: To assess the effectiveness of an intervention including training, provision of written menu feedback, and printed resources on increasing childcare compliance with nutrition guidelines. Design: Parallel group randomized controlled trial. Setting: Hunter New England region, New South Wales, Australia. Participants: Forty-four childcare centers that prepare and provide food on-site to children while in care. Intervention: The intervention was designed using the Theoretical Domains Framework, targeted managers, and cooks and included implementation strategies that addressed identified barriers. Measures: Outcomes included the proportion of menus providing food servings (per child) compliant with overall nutrition guideline recommendations and each individual food group assessed via menu assessments. Cook knowledge of recommendations, intervention acceptability, adverse events, and barriers were also assessed via questionnaires with cooks and managers. Analysis: Logistic regression models, adjusted for baseline values of the outcome. Results: At baseline and follow-up, zero centers in the intervention and control groups were compliant with the overall menu guidelines or for the vegetable and meat food groups. Follow-up between-group differences in compliance for discretionary (33.3 vs 5, P = .18), dairy (41.7 vs 15, P = .16), breads and cereals (8.3 vs 10 P = 1.00), and fruit (16.7 vs 10, P = .48) were all nonsignificant. Relative to the control group, intervention centers showed a significantly greater increase in percentage of cooks with correct knowledge for vegetable servings (93.3 vs 36.4, P = .008). Conclusion: Although the application of the theoretical framework produced a broader understanding of the determinants of menu compliance, due to the complexity of guidelines, limited follow-up support, lower training uptake, and low intervention dose, the intervention was not effective in supporting the practice change required.

Citation Advantage of Promoted Articles in a Cross-Publisher Distribution Platform: 36-month Follow-up to a Randomized Controlled Trial (Preprint)

2021 ◽  
Author(s):  
Paul Kudlow ◽  
Tashauna Brown
Keyword(s):  
Randomized Controlled Trial ◽  
Controlled Trial ◽  
Control Group ◽  
Digital Tool ◽  
Randomized Controlled ◽  
Subject Areas ◽  
The Subject ◽  
The Difference ◽  
Citation Advantage

BACKGROUND There are limited evidence-based strategies that have been shown to increase the rate at which peer-reviewed articles are cited. In a previously reported randomized controlled trial we demonstrated that promotion of article links in an online cross-publisher distribution platform (TrendMD) persistently augments citation rates after 12 months, leading to a statistically significant, 50% increase in citations relative to control. OBJECTIVE To investigate if the citation advantage of promoted articles upholds after 36-months. METHODS Three thousand two hundred articles published in 64 peer-reviewed journals across eight subject areas were block randomized at the subject level to either the TrendMD group (n=1600) or the control group (n=1600) of the study. Articles were promoted in the TrendMD Network for 6 months. We compared the citation rates in both groups after 36 months. RESULTS At 36 months, we found the citation advantage endured; articles randomized to TrendMD showed a 28% increase in mean citations relative to control. The difference in mean citations at 36 months for articles randomized to TrendMD versus control was 10.52, 95% CI [3.79, 17.25] and was statistically significant (p=0.001). CONCLUSIONS To our knowledge, this is the first randomized controlled trial to demonstrate how a post-publication article promotion intervention can be used to persistently augment citations of peer-reviewed articles. TrendMD is an efficient digital tool for knowledge translation and dissemination to targeted audiences to facilitate uptake of research.

Manganese and Lipoflavonoid Plus® to Treat Tinnitus: A Randomized Controlled Trial

2016 ◽  
Vol 27 (08) ◽  
pp. 661-668 ◽  
Author(s):  
Eveling Rojas-Roncancio ◽  
Richard Tyler ◽  
Hyung-Jin Jun ◽  
Tang-Chuan Wang ◽  
Haihong Ji ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Controlled Trial ◽  
Control Group ◽  
Randomized Controlled ◽  
Data Collection And Analysis ◽  
Loudness Match ◽  
Minimal Masking Level ◽  
Lost To Follow Up ◽  
To Receive

Background: Several tinnitus sufferers suggest that manganese has been helpful with their tinnitus. Purpose: We tested this in a controlled experiment where participants were committed to taking manganese and Lipoflavonoid Plus® to treat their tinnitus. Research Design: Randomized controlled trial. Study Sample: 40 participants were randomized to receive both manganese and Lipoflavonoid Plus® for 6 months, or Lipoflavonoid Plus® only (as the control). Data Collection and Analysis: Pre- and postmeasures were obtained with the Tinnitus Handicap Questionnaire, Tinnitus Primary Functions Questionnaire, and tinnitus loudness and annoyance ratings. An audiologist performed the audiogram, the tinnitus loudness match, and minimal masking level. Results: Twelve participants were dropped out of the study because of the side effects or were lost to follow-up. In the manganese group, 1 participant (out of 12) showed a decrease in the questionnaires, and another showed a decrease in the loudness and annoyance ratings. No participants from the control group (total 16) showed a decrease in the questionnaires ratings. Two participants in the control group reported a loudness decrement and one reported an annoyance decrement. Conclusions: We were not able to conclude that either manganese or Lipoflavonoid Plus® is an effective treatment for tinnitus.

scholarly journals Mindfulness-Based Program Plus Amygdala and Insula Retraining (MAIR) for the Treatment of Women with Fibromyalgia: A Pilot Randomized Controlled Trial

2020 ◽  
Vol 9 (10) ◽  
pp. 3246
Author(s):  
Juan P. Sanabria-Mazo ◽  
Jesus Montero-Marin ◽  
Albert Feliu-Soler ◽  
Virginia Gasión ◽  
Mayte Navarro-Gil ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Controlled Trial ◽  
Post Treatment ◽  
Effect Sizes ◽  
Control Group ◽  
Active Control Group ◽  
Treatment As Usual ◽  
Randomized Controlled ◽  
Pilot Randomized Controlled Trial

The lack of highly effective treatments for fibromyalgia (FM) represents a great challenge for public health. The objective of this parallel, pilot randomized controlled trial (RCT) was two-fold: (1) to analyze the clinical effects of mindfulness plus amygdala and insula retraining (MAIR) compared to a structurally equivalent active control group of relaxation therapy (RT) in the treatment of FM; and (2) to evaluate its impact on immune-inflammatory markers and brain-derived neurotrophic factor (BDNF) in serum. A total of 41 FM patients were randomized into two study arms: MAIR (intervention group) and RT (active control group), both as add-ons of treatment as usual. MAIR demonstrated significantly greater reductions in functional impairment, anxiety, and depression, as well as higher improvements in mindfulness, and self-compassion at post-treatment and follow-up, with moderate to large effect sizes. Significant decreases in pain catastrophizing and psychological inflexibility and improvements in clinical severity and health-related quality of life were found at follow-up, but not at post-treatment, showing large effect sizes. The number needed to treat was three based on the criteria of ≥50% Fibromyalgia Impact Questionnaire (FIQ) reduction post-treatment. Compared to RT, the MAIR showed significant decreases in BDNF. No effect of MAIR was observed in immune-inflammatory biomarkers (i.e., TNF-α, IL-6, IL-10, and hs-CRP). In conclusion, these results suggest that MAIR, as an adjuvant of treatment-as-usual (TAU), appears to be effective for the management of FM symptoms and for reducing BDNF levels in serum.

scholarly journals Guided web-based treatment program for reducing cannabis use: a randomized controlled trial

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Kristina Sinadinovic ◽  
Magnus Johansson ◽  
Ann-Sofie Johansson ◽  
Thomas Lundqvist ◽  
Philip Lindner ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Treatment Program ◽  
Controlled Trial ◽  
Cannabis Use ◽  
Control Group ◽  
Web Based ◽  
Randomized Controlled ◽  
Intervention Adherence ◽  
Group Effects

Abstract Background The aim of this study was to investigate the effects of a web-based treatment program with therapist guidance for adults and adolescents with regular cannabis use from the general population. Methods A double blinded randomized controlled trial with a parallel group design was conducted (intervention group n = 151, wait-list control group n = 152). Follow-up 12 weeks from treatment commencement of a 13-module intervention. The primary outcome was frequency of cannabis use. Time by group interaction effects were modeled using generalized estimated equations and the instrumental variable approach was used to estimate the effect of intervention adherence. Results At follow-up, the intention to treat (ITT) analyses did not show any significant time by group effects. A significant association between intervention adherence and scores on the cannabis abuse screening test (CAST) was found. Secondary analysis excluding participants who had received other professional help revealed time by group effects for secondary outcomes gram cannabis consumed past week, number of dependency criteria and CAST score. Due to methodological limitations, these latter results should be interpreted with caution. Conclusions In this study we did not find a web-based treatment program with therapist guidance to be more effective than a waiting-list in reducing frequency of cannabis use. Trial registration The trial was pre-registered at ClinicalTrials.gov (NCT02408640) April 3, 2015

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