Effect of Opioid Infusion Rate on Abuse Liability Potential and Analgesic Efficacy of Intravenous Hydromorphone Among Inpatients With Cancer Pain: A Randomized Crossover Trial
Trial Snapshot
- Phase
- Phase 4
- Status
- Active, not recruiting
- Sponsor
- M.D. Anderson Cancer Center
- Enrollment
- 84
- Locations
- 2
- Primary Endpoint
- Abuse liability potential of SH bolus versus FH bolus (from the "DRUG LIKING" scale of the DEQ questionnaire)
Study Overview
Brief Summary
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
Detailed Description
PRIMARY OBJECTIVE:
I. To compare the abuse liability potential of slow intravenous (IV) hydromorphone bolus infusion rate with fast IV hydromorphone bolus infusion rate among inpatients with breakthrough cancer pain (from the "DRUG LIKING" scale of the Drug Effects Questionnaire [DEQ] questionnaire).
SECONDARY OBJECTIVES:
I. To compare the abuse liability potentials of slow IV hydromorphone bolus with fast IV hydromorphone bolus among inpatients with breakthrough cancer pain (from the other scales of the DEQ questionnaire).
II. To compare the analgesic efficacy of slow IV hydromorphone bolus with fast IV hydromorphone bolus among inpatients with breakthrough cancer pain.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Supportive Care
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
Participants and study staff
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Hospitalized patients with diagnosis of cancer
- •History of moderate to severe cancer related pain, defined as Numerical Rating Scale (NRS) pain score >= 4/10
- •Receiving no or only on as needed doses of opioids
- •Normal cognitive status, defined as a normal state of arousal and an absence of obvious clinical findings of confusion, memory deficits or concentration deficits or a Memorial Delirium Assessment Scale (MDAS) score of < 13
- •Ability to read and communicate in the English language
- •Written informed consent from patient
Exclusion Criteria
- •Contraindications to opioids, or history of opioid allergy
- •Inability to secure IV access
- •Known history or evidence of nonmedical opioid use (e.g. abuse, misuse, addiction)
- •Oxygen saturations < 92% or respiratory rate < 12 breaths/minute on initial assessment
- •Resting heart rate > 120 on initial assessment
- •Systolic blood pressure > 180 < 90 mmHg or diastolic pressure > 100 < 60 mmHg on initial assessment
- •Patients receiving scheduled chronic opioid therapy (defined as the treatment of pain with opioids for >= 7 days)
- •Moderate to severe renal insufficiency (defined as glomerular filtration rate [GFR] < 60 ml/min/1.73 m^2)
- •Hepatic insufficiency (defined as alanine aminotransferase [ALT] or aspartate aminotransferase [AST] > 3 times the highest normal value, or total bilirubin > 1.5 times the highest normal value)
Arms & Interventions
Group A (hydromorphone, placebo)
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.
Intervention: Placebo Administration (Drug)
Group B (hydromorphone, placebo)
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.
Intervention: Hydromorphone (Drug)
Group A (hydromorphone, placebo)
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.
Intervention: Hydromorphone (Drug)
Group A (hydromorphone, placebo)
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.
Intervention: Questionnaire Administration (Other)
Group B (hydromorphone, placebo)
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.
Intervention: Placebo Administration (Drug)
Group B (hydromorphone, placebo)
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.
Intervention: Questionnaire Administration (Other)
Outcomes
Primary Outcomes
Abuse liability potential of SH bolus versus FH bolus (from the "DRUG LIKING" scale of the DEQ questionnaire)
Time Frame: From baseline up to 120 minutes post intervention
This will be measured by: The difference of peak AL scores (maximum score assessed among the measures at 15, 30, 60, and 120 minutes per participant) of the 'drug LIKING' scale in the DEQ-5 questionnaire between the two treatment groups. (For each patient: difference = Max Scale SH+FP - Max Scale FH+SP). If no evidence of carryover effect, a paired t-test will be used. Otherwise a 2-sample t-test will be used only examining differences during the first period of treatment.
Secondary Outcomes
- Adverse effect(From baseline up to 120 minutes post-intervention)
- Plasma concentration (Cmax) and peak (maximal) plasma concentration (Tmax) of hydromorphone metabolite H3G(From baseline up to 120 minutes post-intervention)
- Abuse liability potential among patients who achieved successful analgesia(From baseline up to 120 minutes post-intervention)
- Abuse liability potentials of SH bolus versus FH bolus (from the other scales of the DEQ questionnaire)(From baseline up to 120 minutes post intervention)
- Wild-type or single nucleotide polymorphisms (SNiPs) in UGT enzymes in the study population(From baseline up to 120 minutes post-intervention)
- Analgesic efficacy(From baseline up to 120 minutes post-intervention)
- Elimination half-life (T1/2) of hydromorphone and its metabolite H3G(From baseline up to 120 minutes post-intervention)
- Area-under-the-curve (AUC) of hydromorphone and its metabolite H3G(From baseline up to 120 minutes post-intervention)
- Metabolic ratio of H3G to hydromorphone(From baseline up to 120 minutes post-intervention)