Clinical trial NCT04296305: Effect of Opioid Infusion Rate on Abuse Liability Potential of Intravenous Hydromorphone for Cancer Pain
Official title: Effect of Opioid Infusion Rate on Abuse Liability Potential and Analgesic Efficacy of Intravenous Hydromorphone Among Inpatients With Cancer Pain: A Randomized Crossover Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Hematopoietic and Lymphoid Cell Neoplasm
Malignant Solid Neoplasm
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2020-03-05
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

III. To compare the adverse effects of slow IV hydromorphone bolus with fast IV hydromorphone bolus among inpatients with breakthrough cancer pain.

IV. To explore the abuse liability potential of slow IV hydromorphone bolus with fast IV hydromorphone bolus among the sub group of patients who achieved successful analgesia, defined as at least a two point or 30% reduction in pain intensity score on a 0-10 scale.

V. To obtain exploratory data regarding the relationship between pharmacogenetics and pharmacokinetic (PK) and pharmacodynamic (PD) effects of hydromorphone.

OUTLINE: Patients are randomized to 1 of 2 groups.

GROUP A:

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

TREATMENT PHASE II: Patients are then crossed over to concurrently receive IV hydromorphone over 15 minutes and IV placebo over 2 minutes.

GROUP B:

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

TREATMENT PHASE II: Patients are then crossed over to concurrently receive IV hydromorphone over 2 minutes and IV placebo over 15 minutes.

Eligibility criteria: 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)

Primary outcomes:
measure: Abuse liability potential of SH bolus versus FH bolus (from the "DRUG LIKING" scale of the DEQ questionnaire)
timeFrame: From baseline up to 120 minutes post intervention
Secondary outcomes:
measure: Abuse liability potentials of SH bolus versus FH bolus (from the other scales of the DEQ questionnaire)
timeFrame: From baseline up to 120 minutes post intervention
measure: Analgesic efficacy
timeFrame: From baseline up to 120 minutes post-intervention
measure: Adverse effect
timeFrame: From baseline up to 120 minutes post-intervention
measure: Abuse liability potential among patients who achieved successful analgesia
timeFrame: From baseline up to 120 minutes post-intervention
measure: Plasma concentration (Cmax) and peak (maximal) plasma concentration (Tmax) of hydromorphone metabolite H3G
timeFrame: From baseline up to 120 minutes post-intervention
measure: Elimination half-life (T1/2) of hydromorphone and its metabolite H3G
timeFrame: From baseline up to 120 minutes post-intervention
measure: Area-under-the-curve (AUC) of hydromorphone and its metabolite H3G
timeFrame: From baseline up to 120 minutes post-intervention
measure: Metabolic ratio of H3G to hydromorphone
timeFrame: From baseline up to 120 minutes post-intervention
measure: Wild-type or single nucleotide polymorphisms (SNiPs) in UGT enzymes in the study population
timeFrame: From baseline up to 120 minutes post-intervention
Other outcomes:
Locations:
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Joseph A Arthur, MD
role: PRINCIPAL_INVESTIGATOR
References: