Scopolaminebutyl given prophylactically for death rattle: study protocol of a randomized double-blind placebo-controlled trial in a frail patient population (the SILENCE study)

Abstract

BackgroundDeath rattle (DR), caused by mucus in the respiratory tract, occurs in about half of patients who are in the dying phase. Relatives often experience DR as distressing. Anticholinergics are recommended to treat DR, although there is no evidence for the effect of these drugs. Anticholinergic drugs decrease the production of mucus but do not affect existing mucus. We therefore hypothesize that these drugs are more effective when given prophylactically.MethodsWe set up a randomized double-blind, placebo-controlled, multi-center study evaluating the efficacy of prophylactically given subcutaneous scopolaminebutyl for the prevention of DR in the dying phase. The primary outcome is the occurrence of DR defined as grade ≥ 2 according to the scale of Back measured by a nurse at 2 consecutive time points with an interval of 4 h. Secondary outcomes include adverse effects, quality of dying, quality of life in the last three days and bereavement. A sub-study will explore the experience of participating in a clinical trial in the dying phase from the perspective of relatives. Four hospices will include 200 patients.DiscussionThis is the first double-blind placebo-controlled study to prevent DR in patients in the hospice setting. Research in dying patients is challenging. We will apply ethical and organizational strategies as suggested in the literature.Trial registrationThe trial is retrospectively registered in the Dutch Trial register, identifier NTR 6438 June 2017. EudractCT number 2016–002287-14.

Author's Response

“…3 In addition, the authors correctly pointed out that there are high-level systemic review data that outline that, to date, the only real evidence to manage secretions lies with education and support to family members. 4 Our own clinical practice supports the benefits of talking with families and supporting nursing staff. As part of our role in providing consultative palliative care within the inpatient setting in a tertiary referral teaching hospital, we have recently introduced an approach to caring for the dying.…”

“…Of interest, a large study was planned to confirm the observation reported in our study. 4 3. We are aware of a retrospective report on the patient discomfort with suction of secretions, 5 but the outcome depends on how one proceeds.…”

Unanswered questions and future direction in the management of terminal breathlessness in patients with cancer

“…For example, a consensus definition of chronic breathlessness syndrome has widely raised recognition of this hidden discomfort, and led to a number of clinical trials with various treatment modalities 9 14–18. In addition, recent studies on terminal agitation and death rattle have demonstrated the feasibility of RCTs in patients during the last days of life, if appropriate strategies are implemented 22 77 82. Strategies include, but are not limited to, the use of advance or proxy consent, standardisation of care programmes, the application of short observation periods and the use of clinically implemented outcomes 22 75 82.…”

“…In addition, recent studies on terminal agitation and death rattle have demonstrated the feasibility of RCTs in patients during the last days of life, if appropriate strategies are implemented 22 77 82. Strategies include, but are not limited to, the use of advance or proxy consent, standardisation of care programmes, the application of short observation periods and the use of clinically implemented outcomes 22 75 82. While an RCT is the gold standard for demonstrating the efficacy of medication, continuous recording of routinely collected data would also enable researchers to conduct non-randomised comparative studies among treatment modalities.…”

Response to “Hyoscine Butylbromide for the Management of Death Rattle: Sooner Rather Than Later”

“…Currently, we are performing a randomized doubleblind, placebo-controlled, multicenter study evaluating the efficacy of prophylactically given subcutaneous scopolamine butyl: the SILENCE study. 2 The study is conducted in several hospices in The Netherlands. We adapted our research strategies to overcome two important challenges in performing research in patients in the last hours and days of their lives: gatekeeping and patients' informed consent.…”