Impact of Magnesium L-Lactate on Occurrence of Ventricular Arrhythmias
in Patients with Implantable Cardioverter Defibrillators: A Randomized,
Placebo-Controlled Trial

Background: We evaluated the antiarrhythmic efficacy and quality of life (QoL) impact of oral magnesium Llactate on patients with an implantable cardioverter defibrillator (ICD). Methods: This prospective, double-blind, placebo-controlled trial randomized 70 patients with an ICD to receive oral magnesium L-lactate 3 tablets twice daily (504mg elemental magnesium daily) or matching placebo for 12 months. Patients were seen at baseline, 12, 24, 36, and 52 weeks. The primary endpoints were the cumulative occurrence of ICD therapy [either shock or anti-tachycardia pacing (ATP)] or QoL between the groups. Results: Among the 70 randomized patients with a mean ± SD follow-up of 6.4 ± 4.1 months, 10 patients in the placebo group and 8 in the magnesium group experienced either ICD shock or ATP [HR 0.84, 95% CI 0.33 to 2.12; p=0.706]. Without significant arrhythmia suppression, only minimal effects on QoL were seen. Eighty six percent of all patients had serum intracellular magnesium deficiency. Conclusion: In our underpowered trial, patients with ICDs had intracellular magnesium deficiency but oral magnesium Llactate only nonsignificantly reduced the occurrence of ICD therapies and had little impact on HrQoL.

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A randomized, double-blind trial of fluorouracil plus placebo versus fluorouracil plus oral leucovorin in patients with metastatic colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.1993.11.10.1888 ◽

1993 ◽

Vol 11 (10) ◽

pp. 1888-1893 ◽

Cited By ~ 44

Author(s):

L R Laufman ◽

R M Bukowski ◽

M A Collier ◽

B A Sullivan ◽

R A McKinnis ◽

...

Keyword(s):

Colorectal Cancer ◽

Treatment Failure ◽

Metastatic Colorectal Cancer ◽

Response Rate ◽

Controlled Trial ◽

Double Blind ◽

Time To Treatment Failure ◽

To Receive ◽

Toxicity Pattern

PURPOSE A prospectively randomized trial was performed to determine whether the combination of fluorouracil (FU) plus leucovorin (FU-LV) administered orally is more effective than equitoxic FU for patients with metastatic colorectal cancer. PATIENTS AND METHODS A double-blind, placebo-controlled trial design was used to eliminate observer bias. An escalating FU dosing schedule was used to achieve equal toxicity. End points were response, time to treatment failure (TTF), and eight quality-of-life (QL) parameters. A crossover arm allowed FU-treated patients to receive FU-LV combination treatment after treatment failure. RESULTS Response rate was 32% for FU-LV versus 23% for FU (P = .15). Median TTF was 22 versus 16 weeks (P = .27). Median survival time was 44 versus 54 weeks (P = .26). QL was the same for both treatments, except for days of hospitalization, which was greater for FU-LV (P < .001). Toxicities were similar to those previously reported for FU-LV and FU alone. CONCLUSION Oral LV-FU produces the same efficacy and toxicity pattern as has been reported for intravenous LV-FU. When FU-LV is compared with equitoxic doses of FU, there is no difference in patient outcome. These results suggest that patients with advanced disease should receive FU at doses adequate to produce toxicity.

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Azithromycin for chronic eosinophilic rhinosinusitis with nasal polyp: a placebo-controlled trial

Rhinology Journal ◽

10.4193/rhin20.071 ◽

2020 ◽

Vol 0 (0) ◽

pp. 0-0

Author(s):

I.S. De Oliveira ◽

A.F. Guimaraes ◽

G.F. Arantes Pêgas ◽

C.J. Machado ◽

G.D. Cassali ◽

...

Keyword(s):

Nasal Polyp ◽

Nasal Polyps ◽

Therapeutic Option ◽

Controlled Trial ◽

Subjective Improvement ◽

Double Blind ◽

Aspirin Intolerance ◽

Snot 22

BACKGROUND: Chronic eosinophilic rhinosinusitis with nasal polyps (CRSwNP eosinophilic) is characterised by the formation of benign and bilateral nasal polyps. We aimed to compare the effectiveness of azithromycin as an immunomodulator with the use of a placebo in patients presenting with CRSwNP concomitant with asthma and aspirin intolerance after 3 months of treatment and at a 1-year follow-up. METHODOLOGY: We performed a randomised, double-blind, placebo-controlled trial. Patients received 500 mg azithromycin orally three times/week for 12 weeks. Improvement was evaluated by staging, the Sino-Nasal Outcome Test (SNOT-22), and nasal polyp biopsy. Data collected at pretreatment and 3 months posttreatment were compared. Quality of life was evaluated at the 1-year follow-up. RESULTS: Twenty-seven and 21 patients were treated with azithromycin and a placebo, respectively. The medication was well tolerated overall. Twenty patients (74%) in the azithromycin group and three patients (14%) in the placebo group were not refer- red for surgery at the end of the 3-month treatment. Regarding subjective improvement, there was a median decrease only in the azithromycin group, and the between-group difference was significant. SNOT-22 improvement was maintained in the azithromy- cin group at the 1-year follow-up. CONCLUSIONS: Azithromycin could be considered a therapeutic option for patients presenting with CRSwNP concomitant with asthma and aspirin intolerance.

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Cost-Effectiveness of perioperative Vaginally Administered estrogen in postmenopausal women undergoing prolapse surgery (EVA trial): study protocol for a multicenter double-blind randomized placebo-controlled trial

BMC Women s Health ◽

10.1186/s12905-021-01587-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Eva V. Vodegel ◽

Sandra E. Zwolsman ◽

Astrid Vollebregt ◽

Ruben G. Duijnhoven ◽

Judith E. Bosmans ◽

...

Keyword(s):

Quality Of Life ◽

Postmenopausal Women ◽

Controlled Trial ◽

Estrogen Therapy ◽

Double Blind ◽

Pop Surgery ◽

Vaginal Estrogen ◽

Vaginal Estrogen Therapy

Abstract Background Surgery for pelvic organ prolapse (POP) is associated with high recurrence rates. The costs associated with the treatment of recurrent POP are huge, and the burden from women who encounter recurrent POP, negatively impacts their quality of life. Estrogen therapy might improve surgical outcome for POP due to its potential beneficial effects. It is thought that vaginal estrogen therapy improves healing and long-term maintenance of connective tissue integrity. Hence, this study aims to evaluate the cost-effectiveness of perioperative vaginal estrogen therapy in postmenopausal women undergoing POP surgery. Methods The EVA trial is a multi-center double-blind randomized placebo-controlled trial conducted in the Netherlands comparing the effectiveness and costs-effectiveness of vaginal estrogen therapy. This will be studied in 300 postmenopausal women undergoing primary POP surgery, with a POP-Q stage of ≥ 2. After randomization, participants administer vaginal estrogen cream or placebo cream from 4 to 6 weeks preoperative until 12 months postoperative. The primary outcome is subjective improvement of POP symptoms at 1 year follow-up, measured with the Patient Global Impression of Improvement (PGI-I) scale. Secondary outcomes are POP-Q anatomy in all compartments, re-interventions, surgery related complications, general and disease specific quality of life, sexual function, signs and complaints of vaginal atrophy, vaginal pH, adverse events, costs, and adherence to treatment. Follow up is scheduled at 6 weeks, 6 months and 12 months postoperative. Data will be collected using validated questionnaires and out-patient visits including gynecological examination performed by an independent gynecologist. Discussion This study investigates whether perioperative vaginal estrogen will be cost-effective in the surgical treatment of POP in postmenopausal women. It is hypothesized that estrogen therapy will show a reduction in recurrent POP symptoms and a reduction in reoperations for POP, with subsequent improved quality of life among women and cost savings. Trial registrationNetherlands Trial Registry: NL6853; registered 19-02-2018, https://www.trialregister.nl/trial/6853. EudraCT: 2017-003144-21; registered: 24-07-2017.

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Paulinia cupana (Guaraná) purified dry extract (PC-18) for chemotherapy related fatigue in patients solid tumors.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e19552 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e19552-e19552

Author(s):

Adriana Braz Del Giglio ◽

Tatiana Goberstein Lerner ◽

Andrea Thaumaturgo Lera ◽

Henrique Soares Paiva ◽

Bruno Carelli ◽

...

Keyword(s):

Solid Tumors ◽

Controlled Trial ◽

Mean Difference ◽

Double Blind ◽

Dry Extract ◽

Tumor Types ◽

Anxiety Depression ◽

To Receive ◽

Head Neck

e19552 Background: Paulinia cupana (guaraná) is an amazonic plant with stimulant proprieties which was shown previously to be effective for chemotherapy related fatigue in patients with breast cancer in a randomized double blind placebo controlled trial conducted by our group (J Altern Complement Med. 2011;17(6):505-12). Purpose: Extend our study to patients with different tumor types receiving various regimens of chemotherapy, treated with a purified dry extract of Paulinia cupana (PC-18). Methods: We included patients with solid tumors older than 18 years of age who were scheduled to receive systemic chemotherapy. We excluded patients with fibromyalgia and uncontrolled hypothyroidism, depression, anemia, hypertension or cardiac disease. We evaluated basal fatigue with the BFI questionnaire before chemotherapy, and included only patients who had an increase in their BFI score after one week. PC-18 was given at 50 mg PO bid, starting after one week of chemotherapy. We employed the FACIT-F, BFI, Chalder, HADS and PSQI questionnaires to evaluate fatigue, anxiety, depression and sleep quality at one week and after 4 weeks of chemotherapy. Results: 36 patients with a mean age of 54 years, 61 % female, 28% with breast, 22% colorectal, 8.3% lung , 8.3% head/neck, 5.6% ovarian and 27% of other carcinomas were included. Fatigue scores improved significantly when we compared scores of the BFI (mean difference = 19.39; 95%CI 12.4 – 26.37, p < 0.0001), FACIT-F (mean difference = -11.51; 95%CI -19.25 - -3.76, p = 0.0049) and Chalder (mean difference = 4.571; 95% CI 1.86 – 7.28, p = 0.0018) questionnaires. HADS subscales scores of anxiety (p = 0.025) and depression (p = 0.0095) also improved significantly after 3 weeks of PC-18 therapy. PSQI scores did not change significantly (p = 0.26) after 3 weeks of PC-18 treatment. Conclusions: We conclude that Paulinia cupana (Guaraná) PC-18 extract is active for treatment of chemotherapy related fatigue in patients with a variety of solid tumors and also improves their anxiety and depression scores without worsening the quality of their sleep.

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Does biomarker information impact patients’ preferences for therapy?

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.6527 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 6527-6527

Author(s):

Ann H. Partridge ◽

Karen Sepucha ◽

Anne O'Neill ◽

Kathy Miller ◽

Emily Baker ◽

...

Keyword(s):

Breast Cancer ◽

Treatment Preference ◽

Treatment Preferences ◽

Double Blind Trial ◽

Double Blind ◽

Increased Risk ◽

The Impact ◽

To Receive

6527 Background: Biomarker information can risk stratify patients based on potential for benefits/toxicity from therapy. Ideally, a biomarker will identify those who benefit with limited toxicity. However, the impact of biomarkers is unclear when indicting individuals with greatest benefit are also at increased risk for toxicity. Methods: We surveyed participants at 18 month follow-up in the Decision-Making/Quality of Life (DM-QOL) component of ECOG5103, a RCT where patients were randomized to receive adjuvant chemotherapy for breast cancer with either placebo or bevacizumab (in 2 schedules). We asked patients for the preferred treatment in two hypothetical scenarios: 1) preference for chemo A or chemo A + B without biomarker information; 2) preference for chemo A or chemo A+B when participants tested positive for a “B-receptor” which increased both the benefit and toxicity of chemo A+B. McNemar’s test was used to examine changes in preferences. Results: 439 patients completed both scenarios on 18-month survey. The Table shows the treatment preferences in each scenario. The positive biomarker information in scenario 2 led 60/439 (14%) participants to switch their preference. The main reason for treatment preference in scenario 2 was greater benefits of chemo A+B (64%), the lower risks with chemo A (20%) and positive biomarker (10%). Among participants who changed preference, those randomized to receive bevacizumab were more likely to switch to chemo A in scenario 2. Conclusions: Information about a positive biomarker, indicating increased benefit and increased risk from additional chemo, did not significantly change participants’ preferred treatment. All participants were involved in a large placebo controlled double blind trial and the majority (70%) preferred the most aggressive course of treatment in both scenarios. Whether patients not enrolled in the trial would be more sensitive to the increased risk information is unclear. [Table: see text]

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Adherence therapy for people with schizophrenia

The British Journal of Psychiatry ◽

10.1192/bjp.bp.105.019489 ◽

2006 ◽

Vol 189 (6) ◽

pp. 508-514 ◽

Cited By ~ 108

Author(s):

Richard Gray ◽

Morven Leese ◽

Jonathan Bindman ◽

Thomas Becker ◽

Lorenzo Burti ◽

...

Keyword(s):

Quality Of Life ◽

Health Education ◽

Controlled Trial ◽

Clinical Settings ◽

Clinical Instability ◽

Randomised Controlled ◽

To Receive ◽

Adherence Therapy

BackgroundThere is equivocal evidence of the effectiveness of adherence therapy in improving treatment adherence and clinical outcomes for people with schizophrenia.AimsTo evaluate the effectiveness of adherence therapy in improving quality of life for people with schizophrenia.MethodA 52-week, single-blind, multicentre randomised controlled trial of the effectiveness of adherence therapy. Participants were individually randomised to receive eight sessions of adherence therapy or health education. Assessments were undertaken at baseline and at 52-week follow-up.ResultsAdherence therapy was no more effective than health education in improving quality of life.ConclusionsThis effectiveness trial provides evidence for the lack of effect of adherence therapy in people with schizophrenia with recent clinical instability, treated in ordinary clinical settings.

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Tetrodotoxin for Moderate to Severe Cancer-Related Pain: A Multicentre, Randomized, Double-Blind, Placebo-Controlled, Parallel-Design Trial

Pain Research and Management ◽

10.1155/2017/7212713 ◽

2017 ◽

Vol 2017 ◽

pp. 1-7 ◽

Cited By ~ 23

Author(s):

Neil A. Hagen ◽

Lyne Cantin ◽

John Constant ◽

Tina Haller ◽

Gilbert Blaise ◽

...

Keyword(s):

Primary Analysis ◽

Double Blind ◽

Subcutaneous Injections ◽

Primary Endpoints ◽

Clinically Significant ◽

Intent To Treat ◽

To Receive ◽

Treat Population ◽

Analgesic Response

Objective. This study evaluated subcutaneous injections of tetrodotoxin (TTX) for the treatment of moderate to severe, inadequately controlled cancer-related pain.Methods. Eligible patients were randomized to receive TTX (30 μg) or placebo subcutaneously twice daily for four consecutive days. Efficacy was assessed using pain and composite endpoints (including pain and quality of life measures), and safety was evaluated using standard measures.Results. 165 patients were enrolled at 19 sites in Canada, Australia, and New Zealand, with 149 patients in the primary analysis “intent-to-treat” population. The primary analysis supports a clinical benefit of TTX over placebo based on the pain endpoint alone with a clinically significant estimated effect size of 16.2% (p=0.0460). Thepvalue was nominally statistically significant after prespecified (Bonferroni Holm) adjustment for the two primary endpoints but not at the prespecified two-sided 5% level. The mean duration of analgesic response was 56.7 days (TTX) and 9.9 days (placebo). Most common adverse events were nausea, dizziness, and oral numbness or tingling and were generally mild to moderate and transient.Conclusions. Although underpowered, this study demonstrates a clinically important analgesic signal. TTX may provide clinically meaningful analgesia for patients who have persistent moderate to severe cancer pain despite best analgesic care. This clinical study is registered with ClinicalTrials.gov (NCT00725114).

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A 40 Month Double-Blind, Randomized, Placebo-Controlled Trial on the Effect of BCc1 Nanomedicine on Survival of Metastatic and Non-Metastatic Gastric Cancer Patients

10.21203/rs.3.rs-147862/v1 ◽

2021 ◽

Author(s):

Maryam Hafizi ◽

Somayeh Kalanaky ◽

Hassan Moaiery ◽

Sajad Noorian ◽

Maryam Khayamzadeh ◽

...

Keyword(s):

Gastric Cancer ◽

Adverse Events ◽

Cancer Patients ◽

Controlled Trial ◽

Metastatic Gastric Cancer ◽

P Value ◽

Double Blind ◽

Gastric Cancer Patients

Abstract Background: Complementary experiments on nanomedicines as proper candidates for the control and treatment of cancer are widely being conducted nowadays. In the previous study, the effect of BCc1 nanomedicine, which is synthetized based on nanochelating technology, on overall survival (OS) and quality of life of gastric cancer patients was evaluated after 18 months of consumption. The OS of the same patients is reported in this study after 40 months. Methods: A double-blind, randomized, placebo-controlled, parallel, multicenter design was used in this study. 123 metastatic and non-metastatic gastric cancer patients of both genders (between 25 and 85 years old) participated in this experiment to evaluate their OS after consuming BCc1 for 40 months and to identify the adverse events of this nanomedicine. Results: The median OS of metastatic patients was 257 days in the BCc1 group [95% confidence interval (CI): 144. 142-369.858], while it was 161 days in the placebo [95% CI: 118.462-203.538]; hazard ratio (HR): 0.802 [95% CI: 0.483-1.333] (P-Value = 0.395). Similarly, the median OS of non-metastatic patients was 718 days in the BCc1 group [95% CI; 577.706-860.213], while it was 520 days in the placebo [95% CI: 460.280- 580.690]; HR: 0.807 [95% CI: 0.343,1.902] (P-Value = 0.624). There was no evidence of adverse events after 40 months.Conclusion: The OS improvement of metastatic and non-metastatic gastric cancer patients in the previous (18 months of follow-up) and current (40 months of follow-up) studies showed that BCc1 can be used along with base treatments to improve cancer patients’ OS. Trial registration: IRCTID, IRCT2017101935423N1.Registered on 19 October 2017, http://www.irct.ir/ IRCT2017101935423N1.

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A Double-Blind, Randomized, Controlled, Multicenter Safety and Immunogenicity Study of a Refrigerator-Stable Formulation of Zostavax

Clinical and Vaccine Immunology ◽

10.1128/cvi.00310-07 ◽

2007 ◽

Vol 15 (2) ◽

pp. 314-319 ◽

Cited By ~ 43

Author(s):

Larry I. Gilderman ◽

James F. Lawless ◽

Thomas M. Nolen ◽

Tina Sterling ◽

Ruth Z. Rutledge ◽

...

Keyword(s):

Geometric Mean ◽

Enzyme Linked Immunosorbent Assay ◽

Clinical Settings ◽

Double Blind ◽

Varicella Zoster ◽

Adverse Experiences ◽

Primary Endpoints ◽

Current Formulation ◽

To Receive

ABSTRACT The vaccine Zostavax has been shown to prevent herpes zoster (HZ) and postherpetic neuralgia and is recommended for individuals ≥60 years of age. This study compared the safety and the immunogenicity of a refrigerator-stable formulation (Zostavax refrigerated) with those of the current formulation (Zostavax frozen) in subjects ≥50 years of age. Subjects with a negative history for HZ were randomized 1:1 to receive one dose of either formulation. Enrollment was stratified 1:2 by age (50 to 59 years and ≥60 years). Safety was evaluated for 28 days postvaccination. Varicella-zoster virus (VZV) antibody responses were measured by a glycoprotein enzyme-linked immunosorbent assay (gpELISA). The primary endpoints were the VZV antibody geometric mean titer (GMT; day 28), the VZV antibody geometric mean rise (GMR; days 1 to 28), and the incidence of vaccine-related serious adverse experiences (AEs) over 28 days. The refrigerated (n = 182) and frozen (n = 185) formulations induced similar GMTs (727.4 and 834.4 gpELISA units/ml, respectively); the estimated GMT ratio (refrigerated formulation/frozen formulation) was 0.87 (95% confidence interval, 0.71 to 1.07). The GMRs were 2.6- and 2.9-fold, respectively. No vaccine-related serious AEs were reported in either group, and the safety profiles of the formulations were generally similar. The frequencies of injection-site AEs during follow-up were 35.6% and 46.4% in the refrigerated and the frozen formulation groups, respectively, and were generally mild. The frequencies of systemic AEs were similar in the two groups, and those of vaccine-related AEs were ∼6% in both groups. The refrigerator-stable formulation of Zostavax has an acceptable safety profile and is as immunogenic as the frozen formulation; thus, the vaccine may be used in clinical settings where freezer availability is limited.

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Design and conduct of a multicenter randomized clinical trial on the impact of a post-intensive care unit multidisciplinary follow-up on the quality of life (suivi-rea) (Preprint)

10.2196/preprints.30496 ◽

2021 ◽

Author(s):

Friedman Diane ◽

Lamiae Grimaldi ◽

Alain Cariou ◽

Philippe Aegerter ◽

Stéphane Gaudry ◽

...

Keyword(s):

Quality Of Life ◽

Intensive Care ◽

Controlled Trial ◽

Social Evaluation ◽

Double Blind ◽

Icu Discharge ◽

One Year ◽

The Impact

UNSTRUCTURED Introduction: Critically ill patients are at risk to develop a Post-Intensive Care Syndrome (PICS), which is characterized by physical, psychological and cognitive impairments and dramatically impacts the quality of life. No intervention has been shown to improve the quality of life (QoL). Because of the interdependency of its domains, we hypothesized that a medical, psychological and social follow-up would improve the QoL by mitigating the PICS. Methods and analysis: We conducted a multicenter, double-blind, randomized controlled trial comparing a multidisciplinary to a standard post-ICU follow-up. In the intervention arm, multidisciplinary follow-up consisted of medical, psychological and social evaluation at ICU discharge and at 3, 6 and 12 months after ICU discharge. In the placebo group, patients were seen only at 12 months by the multidisciplinary team. The baseline characteristics at ICU discharge were collected in all patients. The primary outcome was the quality of life at one year, assessed with help of EuroQoL 5 dimensions (EQ5D). Secondary outcomes were mortality, cognitive, psychological and functional status, the social and professional reintegration as well as the rate of re-hospitalization and outpatient consultations at one year. The first patient was randomized on 20/12/2012 and the last patient on 01/09/2017 out of 546 patients who were enrolled across 11 ICUs. At present, data management is still ongoing, and all parties involved in the trial remain blinded. Ethics and dissemination – Research Ethics Committee of Saint-Germain-en-Laye, France, initial approval received on 08/07/2011. Results will be disseminated via peer-reviewed publication and presentation at international conferences. Trial registration: Clinicaltrials.gov identifier NCT01796509 (registered on 21/02/2013).

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