Opioids in patients with COPD and refractory dyspnea: literature review and design of a multicenter double blind study of low dosed morphine and fentanyl (MoreFoRCOPD).

BACKGROUND: Refractory dyspnea or breathlessness is a common symptom in patients with advanced chronic obstructive pulmonary disease (COPD), with a high negative impact on quality of life (QoL). Low dosed opioids have been investigated for refractory dyspnea in COPD and other life-limiting conditions, and some positive effects were demonstrated. However, upon first assessment of the literature, the quality of evidence in COPD seemed low or inconclusive, and focused mainly on morphine which may have more side effects than other opioids such as fentanyl. For the current publication we performed a systematic literature search. We searched for placebo-controlled randomized clinical trials investigating opioids for refractory dyspnea caused by COPD. We included trials reporting on dyspnea, health status and/or QoL. Three of fifteen trials demonstrated a significant positive effect of opioids on dyspnea. Only one of four trials reporting on QoL or health status, demonstrated a significant positive effect. Two-thirds of included trials investigated morphine. We found no placebo-controlled RCT on transdermal fentanyl. Subsequently, we hypothesized that both fentanyl and morphine provide a greater reduction of dyspnea than placebo, and that fentanyl has less side effects than morphine. METHODS: We describe the design of a robust, multi-center, double blind, double-dummy, cross-over, randomized, placebo-controlled clinical trial with three study arms investigating transdermal fentanyl 12 mcg/h and morphine sustained-release 10 mg b.i.d. The primary endpoint is change in daily mean dyspnea sensation measured on a numeric rating scale. Secondary endpoints are change in daily worst dyspnea, QoL, anxiety, sleep quality, hypercapnia, side effects, patient preference, and continued opioid use. Sixty patients with severe stable COPD and refractory dyspnea (FEV1 < 50%, mMRC ≥ 3, on optimal standard therapy) will be included. DISCUSSION: Evidence for opioids for refractory dyspnea in COPD is not as robust as usually appreciated. We designed a study comparing both the more commonly used opioid morphine, and transdermal fentanyl to placebo. The cross-over design will help to get a better impression of patient preferences. We believe our study design to investigate both sustained-release morphine and transdermal fentanyl for refractory dyspnea will provide valuable information for better treatment of refractory dyspnea in COPD. Trial registration NCT03834363 (ClinicalTrials.gov), registred at 7 Feb 2019, https://clinicaltrials.gov/ct2/show/NCT03834363 .

Off to a good start after a cancer diagnosis: implementation of a time out consultation in primary care before cancer treatment decision.

PURPOSE: Supportive care for cancer patients may benefit from improving treatment decisions and optimal use of the family physicians' and specialists' strengths. To improve shared decision-making (SDM) and facilitate continuity of primary care during treatment, a cancer care path including a "time out consultation" (TOC) in primary care before treatment decision, was implemented. This study assesses the uptake of a TOC and the added value for SDM. METHODS: For patients with metastatic lung or gastro-intestinal cancer, a TOC was introduced in their care path in a southern region of The Netherlands, from April until October 2016. Uptake of a TOC was measured to reflect on facilitation of continuity of primary care. The added value for SDM and overall experiences were evaluated with questionnaires and semi-structured interviews among patients, family physicians, and specialists. RESULTS: Of the 40 patients who were offered a TOC, 31 (78%) had a TOC. Almost all patients, family physicians, and specialists expressed that they experienced added value for SDM. This includes a stimulating effect on reflection on choice (expressed by 83% of patients) and improved preparation for treatment decision (75% of patients). Overall added value of a TOC for SDM, only evaluated among family physicians and specialists, was experienced by 71% and 86% of these physicians, respectively. CONCLUSION AND IMPLICATIONS FOR CANCER SURVIVORS: The first experiences with a TOC in primary care before cancer treatment decision suggest that it may help to keep the GP "in the loop" after a cancer diagnosis and that it may contribute to the SDM process, according to patients, family physicians, and specialists.