Medicinal Cannabis (MedCan 3): a randomised, multicentre, double-blind, placebo-controlled trial to assess THC/CBD (1:20) to relieve symptom burden in patients with cancer-a study protocol for a randomised controlled trial.

BACKGROUND: Distressing symptoms are common in advanced cancer. Medicinal cannabinoids are commonly prescribed for a variety of symptoms. There is little evidence to support their use for most indications in palliative care. This study aims to assess a 1:20 delta-9-tetrahydrocannabinol/cannabidiol (THC/CBD) cannabinoid preparation in the management of symptom distress in patients with advanced cancer undergoing palliative care. METHODS AND DESIGN: One hundred and fifty participants will be recruited across multiple sites in Queensland, Australia. A teletrial model will facilitate the recruitment of patients outside of major metropolitan areas. The study is a pragmatic, multicenter, randomised, placebo-controlled, two-arm trial of escalating doses of an oral 1:20 THC/CBD medicinal cannabinoid preparation (10 mg THC:200 mg CBD/mL). It will compare the efficacy and safety outcomes of a titrated dose range of 2.5 mg THC/50mgCBD to 30 mg THC/600 mg CBD per day against a placebo. There is a 2-week patient-determined titration phase, to reach a dose that achieves symptom relief or intolerable side effects, with a further 2 weeks of assessment on the final dose. The primary objective is to assess the effect of escalating doses of a 1:20 THC/CBD medicinal cannabinoid preparation against placebo on change in total symptom distress score, with secondary objectives including establishing a patient-determined effective dose, the effect on sleep quality and overall quality of life. Some patients will be enrolled in a sub-study which will more rigorously evaluate the effect on sleep. DISCUSSION: MedCan-3 is a high-quality, adequately powered, placebo-controlled trial which will help demonstrate the utility of a THC:CBD 1:20 oral medicinal cannabis product in reducing total symptom distress in this population. Secondary outcomes may lead to new hypotheses regarding medicinal cannabis' role in particular symptoms or in particular cancers. The sleep sub-study will test the feasibility of using actigraphy and the Insomnia Severity Index (ISI) in this cohort. This will be the first large-scale palliative care randomised clinical trial to utilise the teletrial model in Australia. If successful, this will have significant implications for trial access for rural and remote patients in Australia and internationally. TRIAL REGISTRATION: ANZCTR ACTRN12622000083796 . Protocol number 001/20. Registered on 21 January 2022. Recruitment started on 8 August 2022.

A Multi-Centre COVID-19 Study Examining Symptoms and Medication Use in the Final Week of Life.

CONTEXT: Guidelines exist to direct end-of-life symptom management in COVID-19 patients. However, the real-world symptom patterns, and degree of concordance with guidelines on medication use, and palliative care involvement has received limited attention. OBJECTIVES: To describe the evolution of COVID-19 symptoms, medication used to alleviate these, and degree of palliative care involvement in the final week of life. METHODS: This retrospective study reviewed all COVID-19 inpatient deaths across five metropolitan hospitals in Australia from January 1 to December 31, 2020. Outcome measures were collected at day of death, and days one, two, five and seven before death. These were COVID-19 symptom severity (measured by the Palliative Care Outcome Scale), and use of supportive pharmacological and non-pharmacological therapies. Palliative care referral timepoint was also collected. RESULTS: Within the sample of 230 patients, commonest symptoms were breathlessness, agitation, pain, and respiratory secretions. On day of death, 79% (n = 181) experienced at least one symptom, and 30% (n = 68) experienced severe/extreme symptoms. The use of midazolam, glycopyrrolate, and infusions for symptom management occurred late, less frequently, and at lower doses than suggested in guidelines and other studies. Palliative care referrals were made late, at median three days before death (IQR 1-6 days), and for only half of people dying from COVID-19 (51%; n = 118). CONCLUSION: Symptoms peaked in final three days of life. Earlier use of in fusional and breakthrough medications should be considered in anticipation of symptoms given high likelihood of dying in discomfort. Earlier palliative care referral for high-risk patients should be considered at hospital admission.

A multi-centre study on patients dying from COVID-19: communication between clinicians, patients and their families.

BACKGROUND: COVID-19 has led to challenges in providing effective and timely communication in healthcare. Services have been required to adapt and evolve as successful communication remains core to high-quality patient-centred care. AIM: To describe the communication between admitted patients, their families and clinicians (medical, nursing, allied health) during end-of-life care. METHODS: This retrospective review included all patients (n = 230) who died directly due to COVID-19 at five Melbourne hospitals between 1 January and 31 December 2020. Contacts and modality used (face to face, video, telephone) during the 8 days prior to death were recorded. RESULTS: Patients were predominantly elderly (median age 86 years) and from residential aged care facilities (62%; n = 141). Communication frequency increased the closer the patient was to death, where on day of death, contact between clinicians and patients was 93% (n = 213) clinicians and families 97% (n = 222) and between patients and families 50% (n = 115). Most contact between patients and families was facilitated by a clinician (91.3% (n = 105) day of death) with the most commonly used mode being video call (n = 30 day of death). CONCLUSION: This study is one of the first and largest Australian reports on how communication occurs at the end of life for patients dying of COVID-19. Contact rates were relatively low between patients and families, compared with other cohorts dying from non-COVID-19 related causes. The impact of this difference on bereavement outcomes requires surveillance and attention.

Palliative Care Clinical Trials: Building Capability and Capacity.

Clinical trials are a key component of expanding the evidence base in palliative care. A key strategic objective of the Victorian Comprehensive Cancer Centre (VCCC), a multisite cancer center alliance, was to increase palliative care clinical trial expertise. The palliative care services within the VCCC alliance presented substantial trial development opportunities with large number of patients and established relationships, but few trial-active centers. Objectives: To establish a multi-site "Building Capability in Palliative Care Clinical Trials" program as a service development, and to assess the strategies, activities, and the outcomes resulting from this program. Methods: A series of strategies and activities were developed linked to the key program objectives of increasing the number of clinical sites and skilled clinicians conducting clinical trials, increasing the number of trials available and patients participating, broadening research opportunities in palliative care, and establishing the program sustainability. Results: In the two years of implementation, the program resulted in the establishment and conduct of several Phase 4 postmarketing pharmacovigilance studies, nine Phase 2 and 3 trials across five palliative care services, and a Phase 1 clinical trial. During the program, 150 patients were recruited to clinical trials, and 258 prospective pharmacovigilance monitoring cases were recorded. Five investigator-initiated trials were developed by clinical trial fellows and achieved competitive (n = 3) or commercial (n = 2) funding. Clinicians reported that undertaking clinical trials had increased attention to the evidence base of care provision, and increased service research activity more broadly. Long-term sustainability remains a challenge, particularly in the context of the COVID-19 pandemic. Conclusions: Clinical trials in palliative care services are feasible, acceptable, and result in increased attention to the evidence base of care. The strategies detailing the framework, activities, and outcomes have been collated to facilitate implementation of clinical trials in other sites and with other trial-naive disciplinary groups.

Palliative care and COVID-19 in the Australian context: a review of patients with COVID-19 referred to palliative care.

Objective Palliative care has played a key role in the response to the coronavirus disease 2019 (COVID-19) pandemic in Australia. This review of consecutive patients with COVID-19 referred to the palliative care consultancy service of a tertiary health service in Melbourne describes the palliative care experience with COVID-19 in Australia. Methods The experiences of 55 patients (median age 86 years; interquartile range (IQR) 81-90 years; 55% male; median Charlson comorbidity score 6 (IQR 5-8); 85% with Australia-modified Karnofsky Performance Status ≤50; 67% from residential aged care facilities) were reviewed to collect relevant data points. Results Most patients were referred for end-of-life care with symptoms including dyspnoea (80%) and agitation/delirium (60%). Continuous subcutaneous infusions were commenced in 71% of patients, with the most frequent medications being opioids and benzodiazepines in relatively small doses; 81% required ≤20 mg subcutaneous morphine equivalent and 64% required ≤10 mg subcutaneous midazolam over 24 h. Fifty patients (91%) died in hospital and the median time from palliative care referral to death was 3 days (IQR 1-5 days). Five patients were discharged back to residential aged care facilities. Overall, 80% of referrals were from the aged care team. Conclusion Our patients had similar demographics, symptoms, medication needs and outcomes to patients in similar settings overseas. We found the symptom management of patients with COVID-19 to be generally straightforward. However, the psychosocial needs of patients were predominant and contributed to complexity. This study highlights the need for well-integrated relationships between the palliative care consultancy service and the diverse range of key treating teams involved in the delivery of pandemic health care. What is known about the topic? Palliative care has played a key role in the response to the COVID-19 pandemic in Australia. There is limited research describing the Australian palliative care experience with the COVID-19 pandemic. What does this paper add? Patients with COVID-19 referred to a hospital-based palliative care consultancy service in Australia had similar demographic characteristics, symptoms, medication needs and outcomes to patients with COVID-19 referred to other palliative care services in the UK and the US. There were significant psychosocial issues affecting patients, families and staff in the context of the pandemic. What are the implications for practitioners? This study highlights the need for well-functioning working relationships between the palliative care consultancy service and other hospital teams that can be leveraged at a time of crisis, such as a pandemic, to provide optimal palliative care to patients.

Multidisciplinary Prognostication Using the Palliative Prognostic Score in an Australian Cancer Center.

CONTEXT: Accurate prognostication is important in oncology and palliative care. A multidisciplinary approach to prognostication provides a novel approach, but its accuracy and application is poorly researched. In this study, we describe and analyze our experience of multidisciplinary prognostication in palliative care patients with cancer. OBJECTIVES: To assess our accuracy of prognostication using multidisciplinary team prediction of survival (MTPS) alone and within the Palliative Prognostic (PaP) Score. METHODS: This retrospective study included all new patients referred to a palliative care consultation service in a tertiary cancer center between January 2010 and December 2011. Initial assessment data for 421 inpatients and 223 outpatients were analyzed according to inpatient and outpatient groups to evaluate the accuracy of prognostication using MTPS alone and within the PaP score (MTPS-PaP) and their correlation with overall survival. RESULTS: Inpatients with MTPS-PaP group A, B, and C had a median survival of 10.9, 3.4, and 0.7 weeks, respectively, and a 30-day survival probability of 81%, 40%, and 10%, respectively. Outpatients with MTPS-PaP group A and B had a median survival of 17.3 and 5.1 weeks, respectively, and a 30-day survival probability of 94% and 50%, respectively. MTPS overestimated survival by a factor of 1.5 for inpatients and 1.2 for outpatients. The MTPS-PaP score correlated better than MTPS alone with overall survival. CONCLUSION: This study suggests that a multidisciplinary team approach to prognostication within routine clinical practice is possible and may substitute for single clinician prediction of survival within the PaP score without detracting from its accuracy. Multidisciplinary team prognostication can assist treating teams to recognize and articulate prognosis, facilitate treatment decisions, and plan end-of-life care appropriately. PaP was less useful in the outpatient setting, given the longer survival interval of the outpatient palliative care patient group.