scholarly journals Successful Strategies and Areas of Improvement–Lessons Learned from Design and Conduction of a Randomized Placebo-Controlled Trial in Palliative Care, ‘Palliative-D’

Life ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1233
Author(s):  
Maria Helde Frankling ◽  
Caritha Klasson ◽  
Linda Björkhem-Bergman
Keyword(s):  
Palliative Care ◽  
Clinical Trials ◽  
Metastatic Cancer ◽  
Controlled Trial ◽  
Antibiotic Use ◽  
Lessons Learned ◽  
Next Of Kin ◽  
Double Blind ◽  
Opioid Dose ◽  
Patient Reported

Clinical trials in palliative care are challenging to design and conduct. Burden on patients should be minimized, while gatekeeping by professionals and next-of kin needs to be avoided. Clinical deterioration due to disease progression affects attrition unrelated to intervention, and different care settings complicate comparisons and reduce the generalizability of the results. The aim of this review is to provide advice for colleagues planning to perform clinical trials in palliative care based on our own experiences from performing the Palliative-D study and by a thorough literature review on this topic. The Palliative-D study was a double-blind trial with 244 randomized patients comparing the effect of vitamin D3 to placebo in patients with advanced or metastatic cancer in the palliative phase of their disease trajectory who were enrolled in specialized palliative home care teams. Endpoints were opioid and antibiotic use, fatigue, and QoL. Recruitment was successful, but attrition rates were higher than expected, and we did not reach targeted power. For the 150 patients who completed the study, the completeness of the data was exceptionally high. Rather than patient reported pain, we choose the difference in the mean change in opioid dose between groups after twelve weeks compared to baseline as the primary endpoint. In this paper we discuss challenges in palliative care research based on lessons learned from the “Palliative-D” trial regarding successful strategies as well as areas for improvement.

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.

A review on Remdesivir: A broad-spectrum antiviral molecule for possible COVID-19 treatment

2021 ◽  
Vol 21 ◽  
Author(s):  
Jabeena Khazir ◽  
Tariq Maqbool ◽  
Bilal Ahmad Mir
Keyword(s):  
Clinical Trials ◽  
Broad Spectrum ◽  
Ebola Virus ◽  
Controlled Trial ◽  
In Vivo Studies ◽  
Therapeutic Drug ◽  
Viral Agent ◽  
Double Blind

: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a novel coronavirus strain and the causative agent of COVID-19 was identified to have emerged in Wuhan, China, in December 2019 [1]. This pandemic situation and magnitude of suffering has led to global effort to find out effective measures for discovery of new specific drugs and vaccines to combat this deadly disease. In addition to many initiatives to develop vaccines for protective immunity against SARS-CoV-2, some of which are at various stages of clinical trials researchers worldwide are currently using available conventional therapeutic drugs with potential to combat the disease effectively in other viral infections and it is believed that these antiviral drugs could act as a promising immediate alternative. Remdesivir (RDV), a broad-spectrum anti-viral agent, initially developed for the treatment of Ebola virus (EBOV) and known to show promising efficiency in in vitro and in vivo studies against SARS and MERS coronaviruses, is now being investigated against SARS-CoV-2. On May 1, 2020, The U.S. Food and Drug Administration (FDA) granted Emergency Use Authorization (EUA) for RDV to treat COVID-19 patients [2]. A number of multicentre clinical trials are on-going to check the safety and efficacy of RDV for the treatment of COVID-19. Results of published double blind, and placebo-controlled trial on RDV against SARS-CoV-2, showed that RDV administration led to faster clinical improvement in severe COVID-19 patients compared to placebo. This review highlights the available knowledge about RDV as a therapeutic drug for coronaviruses and its preclinical and clinical trials against COVID-19.

The research evidence base for homeopathy: a fresh assessment of the literature

Homeopathy ◽  
2003 ◽  
Vol 92 (02) ◽  
pp. 84-91
Author(s):  
RT Mathie
Keyword(s):  
Clinical Trials ◽  
Research Evidence ◽  
Controlled Trial ◽  
Relative Number ◽  
Evidence Base ◽  
Weight Of Evidence ◽  
Clinical Effects ◽  
Upper Respiratory Tract ◽  
Medical Conditions ◽  
Double Blind

Abstract Background. The claims made for the clinical effects of homeopathy are controversial. The results of several meta-analyses of clinical trials are positive, but they fail in general to highlight specific medical conditions that respond well to homeopathy. Aims. This review examines the cumulative research from randomised and/or double-blind clinical trials (RCTs) in homeopathy for individual medical conditions reported since 1975, and asks the question: What is the weight of the original evidence from published RCTs that homeopathy has an effect that is statistically significantly different from that in a comparative group? Method. Analysis of the 93 substantive RCTs that compare homeopathy either with placebo or another treatment. Results. 50 papers report a significant benefit of homeopathy in at least one clinical outcome measure, 41 that fail to discern any inter-group differences, and two that describe an inferior response with homeopathy. Considering the relative number of research articles on the 35 different medical conditions in which such research has been carried out, the weight of evidence currently favours a positive treatment effect in eight: childhood diarrhoea, fibrositis, hayfever, influenza, pain (miscellaneous), side-effects of radio- or chemotherapy, sprains and upper respiratory tract infection. Based on published research to date, it seems unlikely that homeopathy is efficacious for headache, stroke or warts. Insufficient research prevents conclusions from being drawn about any other medical conditions. Conclusions. The available research evidence emphasises the need for much more and better-directed research in homeopathy. A fresh agenda of enquiry should consider beyond (but include) the placebo-controlled trial. Each study should adopt research methods and outcome measurements linked to a question addressing the clinical significance of homeopathy's effects.

scholarly journals Does acupressure help reduce nausea and vomiting in palliative care patients? A double blind randomised controlled trial

2020 ◽  
pp. bmjspcare-2020-002434
Author(s):  
Paul Perkins ◽  
Anne Parkinson ◽  
Rebecca Parker ◽  
Alison Blaken ◽  
Ralph K Akyea
Keyword(s):  
Palliative Care ◽  
Randomised Controlled Trial ◽  
Advanced Cancer ◽  
Controlled Trial ◽  
Acupuncture Point ◽  
Nausea And Vomiting ◽  
Specialist Palliative Care ◽  
Double Blind ◽  
Anticancer Treatment ◽  
Randomised Controlled

IntroductionNausea and vomiting are common symptoms for patients with advanced cancer. While there is evidence for acupuncture point stimulation for treatment of these symptoms for patients having anticancer treatment, there is little for when they are not related to such treatment.ObjectiveTo determine whether acupressure at the pericardium 6 site can help in the treatment of nausea and vomiting suffered by palliative care patients with advanced cancer.Materials and methodsDouble blind randomised controlled trial—active versus placebo acupressure wristbands. In-patients with advanced cancer in two specialist palliative care units who fitted either or both of the following criteria were approached: Nausea that was at least moderate; Vomiting daily on average for the prior 3 days.Results57 patients were randomised to have either active or placebo acupressure wristbands. There was no difference in any of the outcome measures between the two groups: change from baseline number of vomits; Visual Analogue Scale for ‘did acupressure wristbands help you to feel better?’; total number of as needed doses of antiemetic medication; need for escalation of antiemetics.ConclusionsIn contrast to a previously published feasibility study, active acupressure wristbands were no better than placebo for specialist palliative care in-patients with advanced cancer and nausea and vomiting.

scholarly journals Results and lessons learnt from a randomized controlled trial: prophylactic treatment of vestibular migraine with metoprolol (PROVEMIG)

Trials ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Otmar Bayer ◽  
◽  
Christine Adrion ◽  
Amani Al Tawil ◽  
Ulrich Mansmann ◽  
...  
Keyword(s):  
Prophylactic Treatment ◽  
Controlled Trial ◽  
Psychometric Evaluation ◽  
Vestibular Migraine ◽  
Phase Iii ◽  
University Hospitals ◽  
Double Blind ◽  
Treatment Benefit ◽  
Episodic Vertigo ◽  
Patient Reported

Abstract Background Vestibular migraine (VM) is the most frequent cause of recurrent spontaneous attacks of vertigo causally related to migraine. The objective of the Prophylactic treatment of vestibular migraine with metoprolol (PROVEMIG) trial was to demonstrate that metoprolol succinate is superior to placebo in the prevention of episodic vertigo- and migraine-related symptoms in patients with VM. Methods This phase III, two-arm, parallel-group, double-blind, randomized placebo-controlled trial was designed to be conducted at tertiary referral centres at neurology and ear, nose and throat departments of eight German university hospitals. The planned sample size was a total of 266 patients to be allocated. Adults aged 18 years or above diagnosed with probable or definitive VM according to the Neuhauser criteria 2001 were randomly assigned 1:1 to 6 months blinded metoprolol (maintenance dosage of 95 mg daily) or placebo. The primary efficacy outcome was the self-reported number of vertiginous attacks per 30 days documented by means of a paper-based daily symptom diary. The pre-specified time period of primary interest was defined as months 4 to 6. Secondary outcomes included the patient-reported number of migraine days and vertigo days, the Dizziness Handicap Inventory, and clinical assessments. Adverse events were reported throughout the whole 9-month study period. Results At the time of trial termination, no evidence for a difference in the incidence of vertiginous attacks between groups was detected. For the full analysis set, the incidence rate ratio was 0.983 (95% confidence interval (CI) 0.902–1.071) for metoprolol versus placebo. In both groups, there was a significant decline over time in the overall monthly vertigo attacks by a factor of 0.830 (95% CI 0.776–0.887). Results were consistent for all subjective and objective key measures of efficacy. The treatment was well tolerated with no unexpected safety findings. Conclusions After randomizing 130 patients PROVEMIG had to be discontinued because of poor participant accrual not related to the tolerability of the study medication or safety concerns; no treatment benefit of metoprolol over placebo could be established. Additional preparatory work is much needed in the development, psychometric evaluation and interpretation of clinically meaningful end points in trials on episodic syndromes like VM taking into consideration the complexity of this disease entity comprising two domains (vertigo- and headache-related disability). Trial registration EudraCT, 2009-013701-34. Prospectively registered on 8 April 2011.

scholarly journals Efficacy and safety of abatacept in active primary Sjögren’s syndrome: results of a phase III, randomised, placebo-controlled trial

2020 ◽  
pp. annrheumdis-2020-218599
Author(s):  
Alan N Baer ◽  
Jacques-Eric Gottenberg ◽  
E William St Clair ◽  
Takayuki Sumida ◽  
Tsutomu Takeuchi ◽  
...  
Keyword(s):  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Controlled Trial ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Phase Iii ◽  
Open Label ◽  
Double Blind ◽  
Patient Reported ◽  
Sjögren‘S Syndrome

ObjectivesTo evaluate efficacy and safety of abatacept in adults with active primary Sjögren’s syndrome (pSS) in a phase III, randomised, double-blind, placebo-controlled trial.MethodsEligible patients (moderate-to-severe pSS [2016 ACR/European League Against Rheumatism (EULAR) criteria], EULAR Sjögren’s Syndrome Disease Activity Index [ESSDAI] ≥5, anti-SS-related antigen A/anti-Ro antibody positive) received weekly subcutaneous abatacept 125 mg or placebo for 169 days followed by an open-label extension to day 365. Primary endpoint was mean change from baseline in ESSDAI at day 169. Key secondary endpoints were mean change from baseline in EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) and stimulated whole salivary flow (SWSF) at day 169. Other secondary clinical endpoints included glandular functions and patient-reported outcomes. Selected biomarkers and immune cell phenotypes were examined. Safety was monitored.ResultsOf 187 patients randomised, 168 completed double-blind period and 165 continued into open-label period. Mean (SD) baseline ESSDAI and ESSPRI total scores were 9.4 (4.3) and 6.5 (2.0), respectively. Statistical significance was not reached for primary (ESSDAI −3.2 abatacept vs −3.7 placebo, p=0.442) or key secondary endpoints (ESSPRI, p=0.337; SWSF, p=0.584). No clinical benefit of abatacept over placebo at day 169 was seen with other clinical and PRO endpoints. Relative to baseline, abatacept was associated with significant differences vs placebo in some disease-relevant biomarkers (including IgG, IgA, IgM-rheumatoid factor) and pathogenic cell subpopulations (post hoc analyses). No new safety signals were identified.ConclusionsAbatacept treatment did not result in significant clinical efficacy compared with placebo in patients with moderate-to-severe pSS, despite evidence of biological activity.

scholarly journals Clinical trial design in neurofibromatosis type 1 as a model for other tumor predisposition syndromes

2020 ◽  
Vol 2 (Supplement_1) ◽  
pp. i134-i140
Author(s):  
Andrea M Gross ◽  
Brigitte C Widemann
Keyword(s):  
Clinical Trials ◽  
Neurofibromatosis Type 1 ◽  
Clinical Trial Design ◽  
Neurofibromatosis Type ◽  
Lessons Learned ◽  
Benign Tumors ◽  
Pediatric Cancer Patients ◽  
Patient Reported ◽  
Trial Endpoints

Abstract Up to 10% of all pediatric cancer patients may have an underlying germline mutation which predisposed them to develop a malignancy. With more patients being tested for and diagnosed with genetic tumor predisposition syndromes, there has been improved characterization of their many nonmalignant manifestations. However, designing and implementing clinical trials to treat the nonmalignant tumor and non-tumor manifestations of these syndromes poses many unique challenges. Unlike trials for malignancies where tumor response and survival can be used as straightforward trial endpoints, the nonmalignant manifestations are often chronic, evolve more slowly over time, and may not be immediately life-threatening. Therefore, they will likely require a different approach to both testing and treatment with a focus on more functional and patient-reported outcome trial endpoints. The recent success of treatment trials for the benign tumors plexiform neurofibromas in the tumor predisposition syndrome neurofibromatosis type 1 (NF1) can be used as a model for the development of clinical trials in other tumor predisposition syndromes. In this article, we review the unique challenges associated with targeting the nonmalignant aspects of these conditions as well as some of the lessons learned from the NF1 experience which may be applied to other syndromes in the future.

Peritoneal Ultrafiltration for Heart Failure: Lessons from a Randomized Controlled Trial

2019 ◽  
Vol 39 (5) ◽  
pp. 486-489
Author(s):  
Hari Dukka ◽  
Philip A. Kalra ◽  
Martin Wilkie ◽  
Sunil Bhandari ◽  
Simon J. Davies ◽  
...  
Keyword(s):  
Heart Failure ◽  
Randomized Controlled Trial ◽  
Peritoneal Dialysis ◽  
Short Form ◽  
Controlled Trial ◽  
Severe Heart Failure ◽  
Lessons Learned ◽  
Randomized Controlled ◽  
Ckd Stage ◽  
Patient Reported

Peritoneal ultrafiltration (PuF) has been employed for severe heart failure (HF), but evidence for its benefit is lacking. The Peritoneal Dialysis for Heart Failure (PDHF) study was a multicenter prospective randomized controlled trial which aimed to investigate this issue. The trial stopped early due to inadequate recruitment. We describe methods, trial activity, and lessons learned. The trial aimed to recruit 130 participants with severe diuretic-resistant HF (New York Heart Association [NYHA] 3/4) and chronic kidney disease (CKD) stage 3/4 on optimal medical treatment for ≥ 4 weeks from 6 UK centers. Participants were randomized to either continuation of conventional HF treatment or to additionally receiving PuF (1 overnight exchange using Icodextrin dialysate). Primary outcome was change in 6-minute walk test (6MWT) between baseline and 28 weeks (end of trial). Secondary outcomes were changes in patient reported quality of life as assessed by the Kansas City Cardiomyopathy Questionnaire, short form 36 (SF 36) health survey results, hospitalization, and mortality. Over a 2-year period, 290 patients were screened from which only 20 met inclusion criteria and 10 were recruited. Reasons for ineligibility were fluctuating estimated glomerular filtration rate (eGFR), suboptimal HF treatment, frailty, and patients being too unwell for randomization. Barriers to recruitment included patient frailty, with some participants considered only when they were at end of life, unwillingness to engage in an invasive therapy, and suboptimal coordination between cardiology and renal services. This is a challenging patient group in which to perform research, and lessons learned from the peritoneal dialysis (PD)-HF trial will be helpful in the planning of future studies in this area.

Next steps: Incorporating patient-reported outcomes into palliative care referral for people with advanced breast cancer.

2018 ◽  
Vol 36 (34_suppl) ◽  
pp. 133-133
Author(s):  
Yun Rose Li ◽  
Celine Denise Marquez ◽  
Hope S. Rugo ◽  
Michael W. Rabow ◽  
Laura Esserman
Keyword(s):  
Breast Cancer ◽  
Palliative Care ◽  
Advanced Breast Cancer ◽  
Severity Score ◽  
Patient Reported Outcomes ◽  
Metastatic Cancer ◽  
Advanced Breast ◽  
Patient Specific ◽  
Patient Reported

133 Background: Specialty palliative care (SPC) has been shown to improve quality of life, reduce unnecessary health care utilization, reduce overall costs, and decrease mortality in some settings for patients with advanced or metastatic cancer, however only a small proportion are being promptly referred. As interventions that respond to patient reported outcomes (PROs) have been shown to improve symptoms and decrease mortality, we hypothesized that the rates of SPC referral would be increased by documenting, tracking, and presenting PROs for oncology visits to referring oncologists. Methods: Over a period of 2 months, 74 English-speaking established patients seen in an advanced breast cancer clinic with an embedded SPC service were approached and completed the study. All patients filled out the electronic, validated PROMIS and PRO-CTCAE PRO questionnaires in the waiting room using a touch screen tablet. Results were presented to the oncologist during the encounter if the CTCAE severity score exceeded 3 in at least 1 domain. Patient demographics, clinical features and PC referrals or appointments were assessed via chart review. Results: At baseline, 9 (12.2%) patients scored a minimum of “severe” (4/5 or 5/5) in at least 1 of the 3 anxiety domains; 17 (23.0%) had moderate-severe pain; and 27 (32.1%) reported fatigue. At study entry, 25 patients (33.8%) had been referred previously to the SPC service; 19 had actually been seen (76% of referred). Of the 63 (85.1%) patients with sufficient follow-up, 13 (20.6%) reported at least “severe” in >1 CTCAE domains, 6 (46.2%) of whom were previously referred to SPC. For the remaining 7 patients, median PROMIS T-score and PRO-CTCAE maximum severity score were 58.3 and 3.2, respectively; none were referred to SPC during the follow up period. Conclusions: The choice to refer (or not to refer) a patient to SPC is complex and tied to patient specific factors such as coordinating additional visits and fear of end of life conversations. To enable greater access to SPC, alternative referral mechanisms, such as group-based or personalized patient education, or automatic referrals triggered by evidence of need, may be required. #YRL/CDM contributed equally.

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