De Conno, F., Ripamonti, C., Fagnoni, E., Brunelli, C., Luzzani, M., Maltoni, M., . . . MERITO Study Group. (2008). The MERITO Study: A multicentre trial of the analgesic effect and tolerability of normal-release oral morphine during 'titration phase' in patients with cancer pain. Palliative Medicine, 22(3), 214–221.

To assess the effect and tolerability of oral normal-release morphine (NRM) during the initial phase of the treatment of patients with moderate to severe cancer pain

Eligible patients received oral NRM at a starting dose of 5 or 10 mg every four hours. Patients whose pain was not controlled with World Health Organization (WHO) step I analgesics received 5 mg NRM. Patients who received step II therapy received 10 mg NRM. Patients who did not get satisfactory pain relief during the interval between one dose and the next could take rescue doses of oral NRM, up to one dose every hour; rescue NRM doses were the same as the patient’s regular doses. Dose was retitrated on a daily basis so that the dose of oral NRM to be given in the next 24 hours was based on the total opioid dose (regular plus rescue). If possible, patients completed an ambulatory visit for assessment after two and five days from the beginning of the study. On other days, patients received a telephone call that monitored pain intensity, drug dose, and onset of symptoms.

• The sample was composed of 159 patients; 135 completed the study.
• Mean patient age was 65 years. Age range was 29–87 years.
• Of all patients, 34.6% were female and 65.4% were male.
• All patients had advanced cancer. The sample included multiple diagnoses. The pain score of all patients was 5 or higher for at least 24 hours.

• Multisite
• Outpatient
• Sixteen palliative care centers in Italy

Open-label, phase IV clinical trial

• Numeric Rating Scale (NRS) for pain (0 = no pain, 10 = worst pain possible), as reported in each patient's diary
• Mini Mental State Examination (MMSE) (The number of potential subjects who were excluded was fewer than six.)
• Karnofsky Performance Status Score, as reported in each patient's diary
• NRS regarding morphine dosage and adjunct analgesic therapy
• NRM-related adverse events, presence and frequency of episodic pain
• Score on intensity scale, 1–3 (1 = mild, 2 = moderate, 3 = severe), as assigned during physician assessment at visits, to assess safety of NRM

• Of patients categorized as “intent to treat,” or ITT, a very high percentage (45%) achieved pain control for more than 90% of the follow-up period. Of these patients, 79% achieved pain control within 24 hours after taking the first oral NRM dose; 50% of these patients achieved pain control within the first eight hours.
• Most commonly reported adverse events were somnolence (24% of patients), constipation (22%), vomiting (13%), nausea (10%), and confusion (7%). These events occurred primarily in the first days of treatment. With the exception of constipation, none of the events required treatment. Authors observed no unexpected adverse events.

Oral NRM, administered according to European Association for Palliative Care recommendations, can effectively and rapidly decrease pain intensity. In opioid-naive patients, oral NRM has an acceptable safety profile.

• The study had a risk of bias due to no appropriate control group.
• The study was conducted in 16 palliative care units in Italy. Future researchers should repeat the study in a more general setting and in other countries.

This trial demonstrated that clinicians should begin administering NRM as soon as possible to treatment moderate to severe cancer-related pain instead of waiting until the patient is at an advanced or terminal stage. Through titration, the analgesic treatment was tailored to the patient’s needs, and close evaluation and re-evaluation of pain intensity and frequency helped ensure that the therapy continued to be effective and tolerated. Nurses can advocate for NRM when caring for patients with higher levels of pain, thereby increasing the patient’s level of comfort and optimizing patient-centered treatment.