A Phase 4 interventional study of PecFent and Epistatus and Standard subcutaneous medication in Terminal Cancer, sponsored by Gloucestershire Hospitals NHS Foundation Trust. Completed at 1 site in United Kingdom. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2018-05-09.
Sponsored by Gloucestershire Hospitals NHS Foundation Trust · Phase 4, Interventional, and Treatment
When patients are dying they become unable to take oral medication and if they develop symptoms (e.g. pain or agitation) they need to be given a subcutaneous injection of medication. If they are at home this requires that a District Nurse is called and it can take a long time (sometimes hours) for the Nurse to arrive. This can be a very stressful time for the patient and family.
There are 2 drug preparations which could potentially be given by family members in the home:
Nasal fentanyl (PecFent) Buccal midazolam (Epistatus) If these preparations helped symptoms this would give much quicker symptom control for patients and might mean the District Nurse visit was not needed.
In advance of a community based randomised trial of these modes of administration, it is important to assess the feasibility of such an approach in terms of carer acceptability and patient tolerability as well as determine appropriate sample sizes and sampling methods. There are 2 work packages which would help assess feasibility of a community trial:
This will be an open-label, randomized, controlled feasibility pilot study to evaluate whether using nasal fentanyl (PecFent: 100, 200, 400 or 800 mcg) alone or in combination with buccal midazolam (Epistatus: 2.5, 5 or 10 mg) has the possibility to give better breakthrough symptom control to dying patients when compared with standard subcutaneous medication (Figure 1 A and B).
Each subject and their carers/family members will receive verbal and written information followed by signing of the Informed Consent Forms (ICFs). The study is divided into two arms. In both arms patients will receive standard regular oral or subcutaneous medication for relieving non-breakthrough symptoms. In the standard care arm, patients will receive standard as needed medication (SANM) administered orally, sublingually or subcutaneously for breakthrough symptoms. The experimental arm will consist of two stages: in Stage 1 of the study, PecFent will be given to patients in order to treat breakthrough pain instead of subcutaneous opioids. PecFent will be titrated in order to establish an effective treatment dose to manage pain. SANM administered orally, sublingually or subcutaneously will be used to treat agitation and other symptoms.
After the effective treatment dose of PecFent has been established patients will enter stage 2. Patients will not move to stage 2 if the treatment dose of PecFent is not deemed effective. Stage 2 will test a range of doses of Epistatus in terms of efficacy in treating agitation alone instead of subcutaneous midazolam (or in combination with the effective treatment dose of PecFent for pain and agitation).
SANM will be used to treat other symptoms. Assessment of effectiveness of any as needed medication will be conducted at 30 minutes from administration. If PecFent, Epistatus or a combination of both is ineffective, administration of SANM will be considered. Further opioid cannot be given within one hour but benzodiazepine can be given within 30 minutes as is standard practice in this setting. Thus, patients in the experimental arm will receive symptom relief regardless the efficacy of test drugs.
Gloucestershire Hospitals NHS Foundation Trust is the lead sponsor of 21 studies on the registry; 3 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Adult hospice in-patients fitting the following criteria will be approached to see if they are willing to participate in the study:
Exclusion Criteria:
Medication administered by family / carer for symptoms
Drug: PecFent and Epistatus · Drug: Standard subcutaneous medication
Standard subcutaneous medication - diamophine and / or midazolam administered by nursing staff
Drug: Standard subcutaneous medication
From 28/11/17 following approval from sponsor, ethics committee and MHRA a 3rd observational arm was introduced: Epistatus administered PRN by family / carer for symptoms
Drug: Standard subcutaneous medication · Drug: Epistatus Alone
PecFent will be supplied by Archimedes Pharma as two strengths of nasal spray solution at 1000 or 4000 mcg/mL fentanyl (as citrate). One spray contains 100 mcg or 400 mcg fentanyl (as citrate). Each bottle contains 1.55 ml ensuring delivery of 8 sprays of 100 or 400 mcg fentanyl (as citrate). PecFent is a commercially available product and packaging will be in accordance with the manufacturing authorisations (EU/1/10/644/001, EU/1/10/644/002, EU/1/10/644/005, EU/1/10/644/003, EU/1/10/644/004, EU/1/10/644/006). Epistatus will be supplied by Special Products Ltd. as buccal solution, packed in bottles containing solution for up to 4 x 1 ml doses, as per "Specials" licence. A pack also includes 4 x oral syringes used to administer the solution to the buccal cavity on either side of the mouth.
Also known as: Fentanyl and Midazolam
Subcutaneous as needed medication will include: * Opioids for pain or dyspnoea * Diamorphine * Oxycodone * Fentanyl * Benzodiazepine and / or anti-psychotic for agitation * Midazolam * Levomepromazine * Haloperidol Anti-emetic for nausea * Cyclizine * Metoclopramide * Haloperidol * Levomepromazine * Anti-secretory drug for respiratory secretions * Glycopyrronium * Hyoscine butylbromide * Hyoscine hydrobromide
Also known as: Subcutaneous opioids and midazolam
Epistatus will be supplied by Special Products Ltd. as buccal solution, packed in bottles containing solution for up to 4 x 1 ml doses, as per "Specials" licence. A pack also includes 4 x oral syringes used to administer the solution to the buccal cavity on either side of the mouth.
Also known as: Midazolam
Time to adequate symptom control ('comfortable') from need for breakthrough medication (in minutes) according to patient (where possible), relatives and staff.
Data will be captured by patient and/or carer and/or staff with regard to time from need for breakthrough medication (recognition of symptom) to adequate symptom control ('comfortable').
Time frame: 30 minutes
Time (in minutes) from need for breakthrough medication (recognition of symptom) to administration of drug.
Data will be captured by patient and/or carer and/or staff with regard to time from need for breakthrough medication (recognition of symptom) to administration of drug.
Time frame: 30 minutes
Need for additional oral or subcutaneous medication
Data will be captured by patient and/or carer and/or staff with regard to need for additional oral or subcutaneous medication
Time frame: 30 minutes
Time (in minutes) to recurrence of symptoms according to patient (where possible), relatives and staff
Data will be captured by patient and/or carer and/or staff with regard to symptoms recurring.
Time frame: 4 hours
Patient comfort as measured by the modified Palliative care Outcome Scale Symptom list (POS-S) (patient /carer/ staff versions)
The modified Palliative care Outcome Scale Symptom list (POS-S) (patient /carer/ staff versions) at approximately the same time daily (depending on when family / carers are likely to be present). For this study the Palliative care Outcome Scale Symptom list (known as POS-S) has been modified by removing the question on 'Any other symptoms' and with the addition of the anxiety question from the Integrated Palliative care Outcome Scale (IPOS).
Time frame: 30 minutes
Visual analogue scales for pain and agitation completed by patient (where possible), relatives and staff at baseline (Time 0), 5, 10, 15, 20, 25 and 30 minutes for 1 breakthrough episode per day
Visual analogue scales for pain and agitation completed by patient (where possible), relatives and staff at baseline (Time X), time 0 (dose), 5, 10, 15, 20, 25 and 30 minutes (post-dose calculated from time 0) for 1 breakthrough episode per day
Time frame: 30 minutes
Adverse events
Adverse event information will be collected by research staff.
Time frame: 4 weeks after enrolment
Plan to share: Yes — Happy for researchers to contact us once data has been analysed and published
This study is completed, as verified in May 2018. You cannot join it, but the record below documents what was studied.
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Gloucestershire Hospitals NHS Foundation Trust