Hydromorphone Infusion Rates for Cancer Pain

Overseen By Joseph A Arthur

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Chronic opioids

Disqualifiers: Opioid allergy, Nonmedical opioid use, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

84 Participants Needed

Trial Summary

What is the purpose of this trial?

In cancer inpatient settings, intravenous (IV) opioids are frequently administered in a bolus fashion in order to obtain immediate pain relief. However, data on the abuse liability (AL) potential of IV opioids in cancer patients is limited. No study has investigated the effect of different IV infusion rates on AL potential in patients receiving parenteral opioids for pain control. This phase IV trial will determine the AL potential of a slow IV hydromorphone (SH) bolus administration compared with a fast IV hydromorphone (FH) bolus administration among inpatients with cancer pain. It will also determine the analgesic efficacy and adverse effect profiles of SH versus FH bolus infusions, and explore the relationship between pharmacogenetics and pharmacokinetic (PK) and pharmacodynamic (PD) effects of hydromorphone. This study will eventually help develop evidence-based guidelines regarding the best style of IV opioid administration which will achieve the most optimal pain control while avoiding the undesirable complication of nonmedical opioid use

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does require that you are not on scheduled chronic opioid therapy. If you are only taking opioids as needed, you may still be eligible.

What data supports the effectiveness of the drug hydromorphone for cancer pain?

Research shows that hydromorphone is effective for managing moderate to severe cancer pain, with similar pain relief compared to other opioids like morphine and oxycodone. In a study, 70.2% of patients using hydromorphone achieved significant pain relief, and it was found to be a safe and simple method for pain management in both inpatients and outpatients. ^{1 2 3 4 5}

Is hydromorphone safe for use in humans?

Hydromorphone, used for cancer pain, is generally considered safe, but it can cause side effects like nausea, vomiting, constipation, drowsiness, and dry mouth. Some patients may experience local skin reactions or discomfort with certain infusion methods, but these are usually manageable. ^{6 7 8 9 10}

How is the drug hydromorphone unique for treating cancer pain?

Hydromorphone is unique for treating cancer pain because it can be administered as a continuous subcutaneous infusion, which is a safe and simple method that allows patients to manage their pain effectively at home using a portable device. This method is preferred by patients over traditional parenteral treatments and offers flexibility in pain management. ^{1 7 9 11 12}

Research Team

Joseph Arthur, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for hospitalized cancer patients with moderate to severe pain who haven't been using opioids regularly. They must be able to understand and speak English, give consent, and have normal cognitive function without confusion or memory issues. People can't join if they misuse opioids, have liver or kidney problems, allergies to opioids, unstable vital signs like high heart rate or low oxygen levels.

Inclusion Criteria

I am currently hospitalized and have been diagnosed with cancer.

You don't have any noticeable problems with memory, concentration, or confusion.

Written informed consent from patient

Exclusion Criteria

I cannot take opioids due to allergies or other reasons.

Your heart rate is more than 120 beats per minute when you are not doing any physical activity.

You have a history of using opioids for nonmedical reasons, such as for abusing or misusing them.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase I

Patients receive IV hydromorphone and placebo in a crossover design to assess abuse liability and analgesic efficacy

2 weeks

Multiple visits for drug administration and monitoring

Treatment Phase II

Patients are crossed over to receive the alternate IV hydromorphone and placebo infusion rates

2 weeks

Multiple visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Hydromorphone

Trial Overview The study tests how the speed of giving hydromorphone (an opioid) through an IV affects its potential for abuse in controlling cancer pain. It compares slow versus fast infusion rates of hydromorphone while also looking at pain relief effectiveness and side effects related to different genetic responses.

Participant Groups

Group I: Group B (hydromorphone, placebo) Experimental Treatment 3 Interventions

TREATMENT PHASE I: Patients receive hydromorphone IV over 15 minutes and placebo IV over 2 minutes. TREATMENT PHASE II: Patients receive hydromorphone IV over 2 minutes and placebo IV over 15 minutes.

Group II: Group A (hydromorphone, placebo) Experimental Treatment 3 Interventions

TREATMENT PHASE I: Patients receive hydromorphone IV over 2 minutes and placebo IV over 15 minutes. TREATMENT PHASE II: Patients receive hydromorphone IV over 15 minutes and placebo IV over 2 minutes.

Hydromorphone is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Dilaudid for:

• Moderate to severe pain

Approved in Canada as Hydromorphone for:

• Moderate to severe pain

Approved in European Union as Hydromorphone for:

• Moderate to severe pain

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Hydromorphone is effective and tolerable for managing moderate to severe cancer pain, based on a systematic review of 13 studies involving 1208 patients, but it does not show clear superiority over morphine or oxycodone.

The studies indicated that while hydromorphone and morphine provide similar pain relief, side effects varied slightly but were not consistent, suggesting that hydromorphone can be a viable alternative to traditional opioids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of hydromorphone in cancer pain treatment: a systematic review. Pigni, A., Brunelli, C., Caraceni, A.[2018]

In a study involving 202 participants with severe opioid use disorder, injectable hydromorphone was found to have a better safety profile than diacetylmorphine, with fewer adverse events (AEs) and serious adverse events (SAEs) reported.

Despite both medications being administered under supervision, the diacetylmorphine group experienced higher rates of opioid overdoses, particularly in the first month of treatment, highlighting the importance of careful monitoring in opioid addiction therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of injectable hydromorphone and diacetylmorphine for long-term severe opioid use disorder. Oviedo-Joekes, E., Brissette, S., MacDonald, S., et al.[2018]

A systematic review of 25 studies on opioid use for cancer-related pain revealed a wide range of adverse event (AE) rates, with nausea reported between 3% and 85% and constipation between 5% and 97%, highlighting significant variability in patient experiences.

The review emphasizes that due to the heterogeneity in how AEs are assessed and reported across studies, realistic incidence rates for opioid-related AEs remain unclear, indicating a need for standardized measures in future research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review of Prospective Studies Reporting Adverse Events of Commonly Used Opioids for Cancer-Related Pain: A Call for the Use of Standardized Outcome Measures. Oosten, AW., Oldenmenger, WH., Mathijssen, RH., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Continuous sc infusion of narcotics using a portable disposable device in patients with advanced cancer. [2013]

2. United States pubmed.ncbi.nlm.nih.gov

Intrathecal delivery of hydromorphone vs morphine for refractory cancer pain: a multicenter, randomized, single-blind, controlled noninferiority trial. [2021]

3. England pubmed.ncbi.nlm.nih.gov

The role of hydromorphone in cancer pain treatment: a systematic review. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Continuous intravenous infusion of fentanyl: case reports of use in patients with advanced cancer and intractable pain. [2019]

5. Germany pubmed.ncbi.nlm.nih.gov

Efficacy of opioid rotation to continuous parenteral hydromorphone in advanced cancer patients failing on other opioids. [2021]

6. Ireland pubmed.ncbi.nlm.nih.gov

Safety profile of injectable hydromorphone and diacetylmorphine for long-term severe opioid use disorder. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Inpatient narcotic infusions for patients with cancer pain. [2017]

8. United States pubmed.ncbi.nlm.nih.gov

A Systematic Review of Prospective Studies Reporting Adverse Events of Commonly Used Opioids for Cancer-Related Pain: A Call for the Use of Standardized Outcome Measures. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Comparison of hydromorphone continuous subcutaneous infusion and basal rate subcutaneous infusion plus PCA in cancer pain: a pilot study. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Systemic contact dermatitis from subcutaneous hydromorphone. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Patient-controlled subcutaneous hydromorphone versus continuous subcutaneous infusion for the treatment of cancer pain. [2019]

12. England pubmed.ncbi.nlm.nih.gov

A randomized, double-blind, non-inferiority study of hydromorphone hydrochloride immediate-release tablets versus oxycodone hydrochloride immediate-release powder for cancer pain: efficacy and safety in Japanese cancer patients. [2022]