IV PCA With or Without Continuous Dose vs Oral Opioid to Maintain Analgesia for Severe Cancer Pain After Successful Titration

Sponsor

Fujian Cancer Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04785768

Collaborator

(none)

1,600

Enrollment

Location

Arms

Anticipated Duration (Months)

42.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Based on the previous HMORCT09-2, the results show that IV PCA for analgesia maintenance improvements control of severe cancer pain after successful titration. Therefore, a study is planned to further explore the difference of efficacy and safety between PCA with continuous

bolus dose versus bolus-only.

Condition or Disease	Intervention/Treatment	Phase
Cancer Pain	Drug: Hydromorphone Hydrochloride Injection Drug: Hydromorphone Hydrochloride Injection Drug: Morphine Sulfate Sustained-release Tablets	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

1600 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Intravenous (IV) Patient Controlled Analgesia (PCA) With or Without Continuous Dose vs Oral Opioid to Maintain Analgesia for Severe Cancer Pain After Successful Hydromorphone Titration: a Multi-center, Phase Ⅲ ，Randomized Trial

Anticipated Study Start Date :

May 1, 2021

Anticipated Primary Completion Date :

May 1, 2024

Anticipated Study Completion Date :

Jul 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PCA with continuous + bolus dose （1）Intravenous PCA with hydromorphone after successful titration of 24 hours;（2）PCA hydromorphone with continuous infusion where dose/h was the total equianalgesic over the previous 24h divided by 24 and bolus dosage for breakthrough pain was 10%-20% of the total equianalgesic over the previous 24h；lockout time = 10 minutes；（3）Evaluate every 24 hours and PCA parameters were adjusted according to the dose of the previous day; (4)The treatment regimen was continued for 7 days.	Drug: Hydromorphone Hydrochloride Injection Intravenous PCA with hydromorphone after successful titration of 24 hours.the PCA setting: 1) continuous dose (dose/hours) = the total dosage of hydromorphone in the previous 24 hours/24; 2) bolus dose = 10-20% of the total dosage of hydromorphone in the previous 24 hours; 3) lockout time = 10 minutes; 4）Evaluate every 24 hours and PCA parameters were adjusted according to the dose of the previous day.
Experimental: PCA with bolus-only dose （1）Intravenous PCA with hydromorphone after successful titration of 24 hours; (2)PCA hydromorphone with bolus-only where dosage was 10%-20% of the total equianalgesic over the previous 24h administrated as needed;（3）Evaluate every 24 hours and PCA parameters were adjusted according to the dose of the previous day; (4)The treatment regimen was continued for 7 days.	Drug: Hydromorphone Hydrochloride Injection Intravenous PCA with hydromorphone after successful titration of 24 hours.the PCA setting: 1) continuous dose = 0; 2) bolus dose = 10-20% of the total dosage of hydromorphone in the previous 24 hours: 3) lockout time = 10 minutes; 4)Evaluate every 24 hours and PCA parameters were adjusted according to the dose of the previous day.
Active Comparator: Oral opioid （1）Swift to sustained-release morphine orally as background dose with immediate release morphine orally for breakthrough pain after successful titration of 24 hours；(2)Oral sustained-released morphine where total equianalgesic over the previous 24h/2×75% every 12h/day and immediate-release morphine for breakthrough pain was 10%-20% of the total equianalgesic over the previous 24h； (3)Evaluate every 24 hours and the dose for the next day is adjusted according to the dose of the previous day；(4)The treatment regimen was continued for 7 days.	Drug: Morphine Sulfate Sustained-release Tablets Swift to sustained-release morphine orally as background dose with immediate release morphine orally for breakthrough pain after successful titration of 24 hours. Administration of morphine orally 1) Sustained-release morphine orally (dose/12 hours) = the total equianalgesic of the previous 24 hours/2×75% for day 1; 2）the total equianalgesic of the previous 24 hours/2 for day 2 ; 3）Evaluate every 24 hours and the dose for the next day is adjusted according to the dose of the previous day；4) Immediate release morphine orally = 10-20% of the total equianalgesic of the previous 24 hours;

Arm

Intervention/Treatment

Experimental: PCA with continuous + bolus dose

（1）Intravenous PCA with hydromorphone after successful titration of 24 hours;（2）PCA hydromorphone with continuous infusion where dose/h was the total equianalgesic over the previous 24h divided by 24 and bolus dosage for breakthrough pain was 10%-20% of the total equianalgesic over the previous 24h；lockout time = 10 minutes；（3）Evaluate every 24 hours and PCA parameters were adjusted according to the dose of the previous day; (4)The treatment regimen was continued for 7 days.

Drug: Hydromorphone Hydrochloride Injection

Intravenous PCA with hydromorphone after successful titration of 24 hours.the PCA setting: 1) continuous dose (dose/hours) = the total dosage of hydromorphone in the previous 24 hours/24; 2) bolus dose = 10-20% of the total dosage of hydromorphone in the previous 24 hours; 3) lockout time = 10 minutes; 4）Evaluate every 24 hours and PCA parameters were adjusted according to the dose of the previous day.

Experimental: PCA with bolus-only dose

（1）Intravenous PCA with hydromorphone after successful titration of 24 hours; (2)PCA hydromorphone with bolus-only where dosage was 10%-20% of the total equianalgesic over the previous 24h administrated as needed;（3）Evaluate every 24 hours and PCA parameters were adjusted according to the dose of the previous day; (4)The treatment regimen was continued for 7 days.

Drug: Hydromorphone Hydrochloride Injection

Intravenous PCA with hydromorphone after successful titration of 24 hours.the PCA setting: 1) continuous dose = 0; 2) bolus dose = 10-20% of the total dosage of hydromorphone in the previous 24 hours: 3) lockout time = 10 minutes; 4)Evaluate every 24 hours and PCA parameters were adjusted according to the dose of the previous day.

Active Comparator: Oral opioid

（1）Swift to sustained-release morphine orally as background dose with immediate release morphine orally for breakthrough pain after successful titration of 24 hours；(2)Oral sustained-released morphine where total equianalgesic over the previous 24h/2×75% every 12h/day and immediate-release morphine for breakthrough pain was 10%-20% of the total equianalgesic over the previous 24h； (3)Evaluate every 24 hours and the dose for the next day is adjusted according to the dose of the previous day；(4)The treatment regimen was continued for 7 days.

Drug: Morphine Sulfate Sustained-release Tablets

Swift to sustained-release morphine orally as background dose with immediate release morphine orally for breakthrough pain after successful titration of 24 hours. Administration of morphine orally 1) Sustained-release morphine orally (dose/12 hours) = the total equianalgesic of the previous 24 hours/2×75% for day 1; 2）the total equianalgesic of the previous 24 hours/2 for day 2 ; 3）Evaluate every 24 hours and the dose for the next day is adjusted according to the dose of the previous day；4) Immediate release morphine orally = 10-20% of the total equianalgesic of the previous 24 hours;

Outcome Measures

Primary Outcome Measures

Mean pain score of days 1 to 3 [up to 4 days]
The Numerical Rating Scale (NRS, a score of 0 means no pain and 10 means the most severe) is used to assess the severity of pain. NRS of 24 hours is assessed every day. Mean pain score is a sum of average NRS of Day 1 (D 1) to Day 3 divided by 3 (the day of titration is defined as D0, the first day after titration is defined as D1, the second day after titration is defined as D2, and so on).
Number of Breakthrough cancer Pain (BTcP) [up to 4 days]
Breakthrough cancer Pain (BTcP) is NRS > 3

Secondary Outcome Measures

Mean pain score of days 1 to 6 [up to 7 days]
Mean pain score is a sum of average NRS of D1 to D6 divided by 6

Other Outcome Measures

Number of patients with an average NRS pain score >3 [up to 7 days]
The Numerical Rating Scale (NRS, a score of 0 means no pain and 10 means the most severe) is used to assess the severity of pain.
Number of patients with an average NRS pain score > 6 [up to 7 days]
The Numerical Rating Scale (NRS, a score of 0 means no pain and 10 means the most severe) is used to assess the severity of pain.
Daily opioid dosage [up to 7 days]
Daily opioid dosage
Satisfaction score [up to 7 days]
The satisfaction score of the patients to analgesia was evaluated by 10-point scale: 0 points for dissatisfaction, 10 points for very satisfied, the higher the score, the higher the satisfaction.
Quality of life of patients [up to 7 days]
Chinese version of the Edmonton Symptom Assessment System.
Number of patients who switched/discontinued therapy due to serious adverse events or lack of pain control [up to 7 days]
The number of patients who switched/discontinued therapy due to serious adverse events or lack of pain control

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

The patients were 18-80 years old and diagnosed as malignant solid tumor by pathology;
Patients with persistent cancer pain and NRS score ≥ 7 during previous 24 hours;
Patients who did not receive radiotherapy, chemotherapy or targeted therapy within 7 days before randomization and trial；
Patients or his/her caregivers who are able to fill out the questionnaire forms ;
Ability to correctly understand and cooperate with medication guidance of doctors and nurses ;
Without psychiatric problems;
ECOG performance status ≤3;
Patients who did not receive the trial drug within 14 days before the trial；
The subjects voluntarily signed the informed consent.

Exclusion Criteria:

The pain is confirmed not due to cancer;
Patients with severe post-operative pain;
Patients with paralytic ileus;
Patients with brain metastasis;
Patients hypersensitive to opioids;
Patients with abnormal lab results that have obvious clinical significance, such as creatine ≥ 2 fold of upper limit of normal value, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 2.5 fold of upper limit of normal value, or liver function of Child C grade;
Patients who cannot take drugs orally;
Patients with an incoercible nausea or vomiting;
Those who have received monoamine oxidase inhibitor (MAOI) within two weeks before randomization;
Patients who are pregnant or in lactation, or who plan to be pregnant within one month after the trial;
Alcoholic patients;
Patients with other conditions or reasons causing the patients unable to complete the clinical trial.