Oral Morphine Drops for Rapid Treatment of Breathlessness in Palliative Cancer Patients. A Randomized, Double Blind, Crossover Trial of Morphine Sulfate Oral Solution vs. Morphine Hydrochloride Oral Solution (Red Morphine Drops)

Abstract Background: Idiopathic pulmonary fibrosis (IPF) is a progressive disease that leads to lung scarring, Cough is reported by 85% of patients with IPF and can be a distressing symptom with a significant impact on patients’ quality of life. There are no proven effective therapies for IPF related cough. While morphine is frequently used as a palliative agent for breathlessness in IPF, its effects on cough have never been tested. PAciFy Cough is a multicenter, double-blind, placebo-controlled, crossover trial of morphine sulfate for the treatment of cough in IPF. Methods: We will recruit 44 subjects with IPF prospectively from three interstitial lung disease units in the UK, namely the Royal Brompton Hospital, Manchester University NHS Foundation Trust (MFT) and Aintree University Hospital NHS Foundation Trust. Patients will be randomized (1:1) to either placebo twice daily or morphine sulfate 5mg twice daily for 14 days. They will then crossover after a 7 day washout period. The primary endpoint is the percent change in daytime cough frequency (coughs per hour) from baseline as assessed by objective cough monitoring at Day 14 of treatment.Discussion: This multicentre, randomised trial will assess the effect of opioids on cough counts and cough associated quality of life in IPF subjects. If proven to be an effective intervention, it represents a readily available treatment for patients.Trial registration: The study was approved by the UK Medicines and Healthcare Regulatory Agency (Ref: CTA 21268/0224/001-0001 – EUDRACT 2019-003571-19 – Protocol Number RBH2019/001) on 08 April 2020, in compliance with the European Clinical Trials Directive and the Medicines for Human Use (Clinical Trials) Regulations 2004 and its subsequent amendments. The study was provided with ethical approval by the London Brent Research Ethics Committee (Ref: 20/LO/0368) on 21 May 2020 and is registered with clinicaltrials.gov (NCT04429516) on 12 June 2020, available at https://clinicaltrials.gov/ct2/show/NCT04429516

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Controlled-release oral morphine sulfate in the treatment of cancer pain with pharmacokinetic correlation.

Journal of Clinical Oncology ◽

10.1200/jco.1987.5.6.956 ◽

1987 ◽

Vol 5 (6) ◽

pp. 956-961 ◽

Cited By ~ 33

Author(s):

A Khojasteh ◽

W Evans ◽

R D Reynolds ◽

G Thomas ◽

J J Savarese

Keyword(s):

Controlled Release ◽

Side Effects ◽

Cancer Patients ◽

Peak Plasma ◽

Oral Morphine ◽

Extended Period ◽

Morphine Sulfate ◽

Control Group ◽

Clinical Effects ◽

The Mean

The bioavailability and clinical effects of an oral controlled-release morphine sulfate tablet, MS-contin (MSC; Purdue-Frederick, Norwalk, CT) in comparison to an immediate-release (IRMS) preparation were evaluated in normal subjects and cancer patients, respectively. The inherent slow-release character of MSC was confirmed by 2 1/2 X T1/2 absorption rate, one-half Cmax, and twice Tmax relative to IRMS. The T1/2 elimination of the two morphine preparations was similar, demonstrating insignificant risk of MSC accumulation. The difference in the mean number of side effects experienced by the control group per subject was significant (.70 for MSC and 1.26 for IRMS, P = .05) and was consistent with peak plasma morphine attenuation. The cancer patients were initially switched from their previous analgesic to four hourly IRMS and then to MSC at double the dose every eight hours. The majority had their MSC dosing interval lengthened to every 12 hours with a decrease in the total daily morphine requirement. While the mean duration on MSC was 20.5 days, many patients were followed poststudy for an extended period with no appreciable development of tolerance. Overall, MSC analgesia and side effects were perceived by the patients as superior compared with prestudy opioids. The advantage of less frequent dosing may lead to improvement of the quality of life of cancer patients.

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Double-Blind Crossover Clinical and Pharmacokinetic Comparison of Oral Morphine Syrup and Sustained Release Morphine Sulfate Capsules in Patients with Cancer-Related Pain

Clinical Drug Investigation ◽

10.2165/00044011-199700141-00006 ◽

1997 ◽

Vol 14 (Supplement 1) ◽

pp. 22-27 ◽

Cited By ~ 6

Author(s):

Jean-François Gillette ◽

Christophe Ferme ◽

Nancy Moisy ◽

Laurent Mignot ◽

Roger Schach ◽

...

Keyword(s):

Sustained Release ◽

Oral Morphine ◽

Morphine Sulfate ◽

Double Blind ◽

Patients With Cancer

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Lack of Benefit From Paracetamol (Acetaminophen) for Palliative Cancer Patients Requiring High-Dose Strong Opioids: A Randomized, Double-Blind, Placebo-Controlled, Crossover Trial

Journal of Pain and Symptom Management ◽

10.1016/j.jpainsymman.2009.07.008 ◽

2010 ◽

Vol 39 (3) ◽

pp. 548-554 ◽

Cited By ~ 37

Author(s):

Fiona J. Israel ◽

Greg Parker ◽

Margaret Charles ◽

Liz Reymond

Keyword(s):

Cancer Patients ◽

Crossover Trial ◽

High Dose ◽

Double Blind ◽

Double Blind Placebo ◽

Strong Opioids

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Role of rectal route in treating cancer pain: a randomized crossover clinical trial of oral versus rectal morphine administration in opioid-naive cancer patients with pain.

Journal of Clinical Oncology ◽

10.1200/jco.1995.13.4.1004 ◽

1995 ◽

Vol 13 (4) ◽

pp. 1004-1008 ◽

Cited By ~ 52

Author(s):

F De Conno ◽

C Ripamonti ◽

L Saita ◽

T MacEachern ◽

J Hanson ◽

...

Keyword(s):

Cancer Pain ◽

Cancer Patients ◽

Rectal Administration ◽

Liquid Solution ◽

Onset Of Action ◽

Double Blind ◽

Rectal Route ◽

Significant Difference ◽

Opioid Administration ◽

Morphine Hydrochloride

PURPOSE The aim of this double-blind, double-dummy, crossover study was to compare the efficacy, tolerability, and time of onset of analgesia after the administration of 10 mg of morphine hydrochloride via the oral and rectal routes in opioid-naive cancer patients with pain. PATIENTS AND METHODS Thirty-four patients with cancer pain and no previous opioid treatment were randomized to receive morphine hydrochloride 10 mg orally or rectally (in the form of a microenema) for 2 days. During days 3 and 4, a crossover took place. The scores of pain, nausea, and sedation (visual analog scale of 0 to 100) calculated as the percentage change from baseline (before opioid administration) were assessed at different intervals up to 240 minutes. The number of vomiting episodes was recorded. Parity tests and analysis of variance (ANOVA) were performed to compare the two administration routes. RESULTS A significant difference in pain intensity was achieved 10 minutes after rectal administration compared with 60 minutes after oral administration. There was still a significant reduction in pain via the rectal route after 180 minutes versus via the oral route after 120 minutes. No significant difference was observed in the intensity of sedation, nausea, or number of vomiting episodes between the oral and rectal routes. CONCLUSION A liquid solution of morphine is well absorbed via the rectal route. Rectal morphine is safe, effective, easy to manage, and inexpensive, with a rapid onset of action. Rectal morphine can be considered a valid alternative route for opioid administration and may also be used when rescue doses of morphine are required in patients regularly treated with oral or parenteral opioids.

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