Subcutaneous Lidocaine For Cancer-Related Pain

A Randomized Double Blind Placebo Controlled Crossover Trial of the Use of Subcutaneous Lidocaine Infusion (SCLI) for Chronic Cancer-related Pain

Status

Completed

Phases

Phase 2Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01384877

Enrollment

Registered

2011-06-29

Start date

2011-12-31

Completion date

2019-01-31

Last updated

2019-07-12

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cancer-related Pain

Keywords

Pain, Cancer, Lidocaine, Sodium Channel Blockers

Brief summary

This study's primary objective is to test the hypothesis that a single infusion of subcutaneous lidocaine can cause a clinically useful reduction in cancer pain within 48 hours of infusion and lasting a minimum of 7 days. A clinically useful reduction in pain is defined by either a 2-point reduction (on a 0-10 scale) in the worst pain experienced over a 24-hour period, or a ≥30% reduction in 24-hour opioid requirement. We will use a composite endpoint of reduction in pain without increase in 24-hr opioid requirement or no decrease in pain with a ≥30% reduction in 24-hour opioid requirement.Subjects will receive either lidocaine or placebo, followed at least 1 week later by the alternate agent.

Detailed description

Ten mg/kg of lidocaine will be infused subcutaneously via a Baxter infusor over a 5.5 hour period in ambulatory adult cancer patients with a worst pain score of at least 4 out of 10 despite therapy with at least one opioid plus appropriate oral adjuvant analgesic(s). A clinically useful reduction in pain is defined by either a 2-point reduction (on a 0-10 scale) in the worst pain experienced over a 24-hour period, or a ≥30% reduction in 24-hour opioid requirement. The secondary objectives are 1) to determine whether any significant toxicities occur as a result of the infusion. For this study significant toxicity is considered as any adverse event which either leads to the infusion being terminated, or which leads to medical intervention, such as prescribing of another medication or equivalent treatment, 2) to determine the effect of Lidocaine infusion on QOL parameters as measured by the Patient Outcome Scale (POS) Questionnaire and 3) to determine the duration of response to lidocaine infusion. Subjects will fill out Brief Pain Inventory (BPI), Patient Outcome Scale (POS) periodically and medication logs daily while on study. On Days of treatment the subjects will have vital sign monitoring every 15 minutes for the 1st hour and then periodically as set out in the protocol.

Interventions

DRUGLidocaine

10mg/kg by subcutaneous infusion over 5.5 hours

DRUGPlacebo (D5W)

Same volume as for lidocaine infusion, identical clear liquid in appearance, given in same device over same time period (5.5 hrs)

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

SUPPORTIVE_CARE

Masking

TRIPLE (Subject, Caregiver, Investigator)

Masking description

Double blind performed by pharmacy. Un blinding to occur at end of study. All subjects to be injected with 1 mL of 1% lidocaine subcutaneous prior to the initiation of the study med infusion, which will act as a masking agent.

Intervention model description

One-sided McNemar's tests will be carried out to test whether a single infusion of subcutaneous lidocaine will cause a reduction in cancer pain for both the interim and final analyses at the p-values of 0.00153 and 0.02347 respectively.

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Male or female patients 18 years of age or older * In or outpatients referred to the BCCA PSMPC Clinics with a diagnosis of cancer * Subjects must have somatic, visceral or neuropathic pain related to cancer * Pain intensity, measured by a worst pain score over the last 72 hours of ≥4 on a 0-10 numerical rating scale * Must have tried at least one opioid medication without adequate response or with significant side-effects for at least one week * For those with neuropathic pain, must have also tried at least one adjuvant analgesic, such as a tricyclic (unless contraindicated) or an anticonvulsant without adequate response or with significant side-effects for at least one week * Life expectancy of \> 3 months * Must be able to communicate symptoms indicating potential toxicity of Lidocaine * Must have a competent caregiver in the home overnight after each infusion * Must be willing to remain within 30 minutes of the Cancer Centre during each infusion

Exclusion criteria

* Clinically significant cardiac disease, i.e, cardiac failure, atrial fibrillation with slow ventricular rate (\<60), any degree of heart block * New analgesic treatment initiated in time frame which might have effect within one week of study drug. * Hyper or hypokalemia. * Liver failure (bilirubin ≥ 25 umol/L). * Renal failure (eGFR \<50% of normal) * Uncontrolled hypertension (\>160/90). * Hypotension (systolic \< 90). * Uncontrolled seizures. * Planned initiation of chemotherapy, radiotherapy or bisphosphonates within 30 days prior to treatment with study drug. * Received an investigational drug within 30 days prior to study. * History of allergy to lidocaine or other topical, local or infusional anesthetics.

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Reduction in Worst Pain Intensity or Reduction in 24hr Opioid Dose of at Least 30% Without Worsening of Pain Scores	7 days	The primary outcomes measure is a binary variable indicating whether lidocaine caused a reduction in cancer pain within 48 hours of infusion and lasting a minimum of 7 days. Lidocaine will be considered to have caused reduction in cancer pain if the subject had either one of the following episodes and lasting a minimum of 7 days: 1. A 2-point reduction in severity of pain as assessed by the worst pain score in the last 24 hours (question 3) of the Brief Pain Inventory - Short Form (BPI), compared to the BPI pain score at baseline. Or: 2. ≥30% reduction in 24-hour opioid dose.

Secondary

Measure	Time frame	Description
Quality of Life Question: Over the Past 3 Days, Have You Been Affected by Pain?	At most 6 weeks (duration of study)	Effect of Lidocaine infusion on Quality Of Life parameters as measured by the Patient Outcome Scale (POS) Questionnaire Baseline scores were compared to an average post treatment score (taken immediately post treatment and on days 2, 3, and 7 following treatment) All POS questions were scored from 0 to 4 with lower scores requiring less clinical attention than higher scores
Quality of Life Question: Over the Past 3 Days, Have Other Symptoms e.g. Feeling Sick, Having a Cough or Constipation Been Affecting How You Feel?	At most 6 weeks (duration of study)	Effect of Lidocaine infusion on Quality Of Life parameters as measured by the Patient Outcome Scale (POS) Questionnaire Baseline scores were compared to an average post treatment score (taken immediately post treatment and on days 2, 3, and 7 following treatment) All POS questions were scored from 0 to 4 with lower scores requiring less clinical attention than higher scores
Quality of Life Question: Over the Past 3 Days, Have You Been Feeling Anxious or Worried About Your Illness or Treatment?	At most 6 weeks (duration of study)	Effect of Lidocaine infusion on Quality Of Life parameters as measured by the Patient Outcome Scale (POS) Questionnaire Baseline scores were compared to an average post treatment score (taken immediately post treatment and on days 2, 3, and 7 following treatment) All POS questions were scored from 0 to 4 with lower scores requiring less clinical attention than higher scores
Quality of Life Question: Over the Past 3 Days, Have Any of Your Family or Friends Been Anxious or Worried About You?	At most 6 weeks (duration of study)	Effect of Lidocaine infusion on Quality Of Life parameters as measured by the Patient Outcome Scale (POS) Questionnaire Baseline scores were compared to an average post treatment score (taken immediately post treatment and on days 2, 3, and 7 following treatment) All POS questions were scored from 0 to 4 with lower scores requiring less clinical attention than higher scores
Quality of Life Question: Over the Past 3 Days, Have You Been Able to Share How You Are Feeling With Your Family or Friends?	At most 6 weeks (duration of study)	Effect of Lidocaine infusion on Quality Of Life parameters as measured by the Patient Outcome Scale (POS) Questionnaire Baseline scores were compared to an average post treatment score (taken immediately post treatment and on days 2, 3, and 7 following treatment) All POS questions were scored from 0 to 4 with lower scores requiring less clinical attention than higher scores
Quality of Life Question: Over the Past 3 Days, Have You Been Feeling Depressed?	At most 6 weeks (duration of study)	Effect of Lidocaine infusion on Quality Of Life parameters as measured by the Patient Outcome Scale (POS) Questionnaire Baseline scores were compared to an average post treatment score (taken immediately post treatment and on days 2, 3, and 7 following treatment) All POS questions were scored from 0 to 4 with lower scores requiring less clinical attention than higher scores
Quality of Life Question: Over the Past 3 Days, Have You Felt Good About Yourself as a Person?	At most 6 weeks (duration of study)	Effect of Lidocaine infusion on Quality Of Life parameters as measured by the Patient Outcome Scale (POS) Questionnaire Baseline scores were compared to an average post treatment score (taken immediately post treatment and on days 2, 3, and 7 following treatment) All POS questions were scored from 0 to 4 with lower scores requiring less clinical attention than higher scores
Quality of Life Question: Over the Past 3 Days, How Much Time do You Feel Has Been Wasted on Appointments Relating to Your Healthcare e.g. Waiting Around for Transport or Repeating Tests?	At most 6 weeks (duration of study)	Effect of Lidocaine infusion on Quality Of Life parameters as measured by the Patient Outcome Scale (POS) Questionnaire Baseline scores were compared to an average post treatment score (taken immediately post treatment and on days 2, 3, and 7 following treatment) All POS questions were scored from 0 to 4 with lower scores requiring less clinical attention than higher scores
Quality of Life Question: Over the Past 3 Days, Have Any Practical Matters Resulting From Your Illness, Either Financial or Personal, Been Addressed?	At most 6 weeks (duration of study)	Effect of Lidocaine infusion on Quality Of Life parameters as measured by the Patient Outcome Scale (POS) Questionnaire Baseline scores were compared to an average post treatment score (taken immediately post treatment and on days 2, 3, and 7 following treatment) All POS questions were scored from 0 to 4 with lower scores requiring less clinical attention than higher scores

Countries

Canada

Participant flow

Pre-assignment details

One (1) participant signed the informed consent form but withdrew from the study before receiving any treatment.

Participants by arm

Arm	Count
Lidocaine/Placebo Patient received Lidocaine in the first period followed by placebo in the second period. Lidocaine: 10mg/kg by subcutaneous infusion over 5.5 hours Placebo (D5W): Same volume as for lidocaine infusion, identical clear liquid in appearance, given in same device over 5.5 hrs	17
Placebo (D5W)/Lidocaine Patient received Placebo in the first period followed by Lidocaine in the second period. Placebo (D5W): Same volume as for lidocaine infusion, identical clear liquid in appearance, given in same device over 5.5 hrs Lidocaine: 10mg/kg by subcutaneous infusion over 5.5 hours	16
Total	33

Withdrawals & dropouts

Period	Reason	FG000	FG001
Treatment 2	Lost to Follow-up	2	2

Baseline characteristics

Characteristic	Lidocaine/Placebo	Placebo (D5W)/Lidocaine	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	3 Participants	3 Participants	6 Participants
Age, Categorical Between 18 and 65 years	14 Participants	13 Participants	27 Participants
Palliative Performance Scale 100%	1 Participants	0 Participants	1 Participants
Palliative Performance Scale 60-69%	1 Participants	4 Participants	5 Participants
Palliative Performance Scale 70-79%	8 Participants	8 Participants	16 Participants
Palliative Performance Scale 80-89%	1 Participants	0 Participants	1 Participants
Palliative Performance Scale 90-99%	6 Participants	4 Participants	10 Participants
Race and Ethnicity Not Collected	—	—	0 Participants
Region of Enrollment Canada	17 participants	16 participants	33 participants
Sex: Female, Male Female	7 Participants	9 Participants	16 Participants
Sex: Female, Male Male	10 Participants	7 Participants	17 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	1 / 32	2 / 32
other Total, other adverse events	3 / 32	2 / 32
serious Total, serious adverse events	0 / 32	0 / 32

Outcome results

Primary

Number of Participants With Reduction in Worst Pain Intensity or Reduction in 24hr Opioid Dose of at Least 30% Without Worsening of Pain Scores

The primary outcomes measure is a binary variable indicating whether lidocaine caused a reduction in cancer pain within 48 hours of infusion and lasting a minimum of 7 days. Lidocaine will be considered to have caused reduction in cancer pain if the subject had either one of the following episodes and lasting a minimum of 7 days: 1. A 2-point reduction in severity of pain as assessed by the worst pain score in the last 24 hours (question 3) of the Brief Pain Inventory - Short Form (BPI), compared to the BPI pain score at baseline. Or: 2. ≥30% reduction in 24-hour opioid dose.

Time frame: 7 days

Population: Participants were included in analysis if they completed both treatment periods and all the data was collected for both treatment periods

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Lidocaine/Placebo	Number of Participants With Reduction in Worst Pain Intensity or Reduction in 24hr Opioid Dose of at Least 30% Without Worsening of Pain Scores	Period 1	1 Participants
Lidocaine/Placebo	Number of Participants With Reduction in Worst Pain Intensity or Reduction in 24hr Opioid Dose of at Least 30% Without Worsening of Pain Scores	Period 2	2 Participants
Placebo (D5W)/Lidocaine	Number of Participants With Reduction in Worst Pain Intensity or Reduction in 24hr Opioid Dose of at Least 30% Without Worsening of Pain Scores	Period 2	1 Participants
Placebo (D5W)/Lidocaine	Number of Participants With Reduction in Worst Pain Intensity or Reduction in 24hr Opioid Dose of at Least 30% Without Worsening of Pain Scores	Period 1	2 Participants

Secondary

Quality of Life Question: Over the Past 3 Days, Have Any of Your Family or Friends Been Anxious or Worried About You?

Effect of Lidocaine infusion on Quality Of Life parameters as measured by the Patient Outcome Scale (POS) Questionnaire Baseline scores were compared to an average post treatment score (taken immediately post treatment and on days 2, 3, and 7 following treatment) All POS questions were scored from 0 to 4 with lower scores requiring less clinical attention than higher scores

Time frame: At most 6 weeks (duration of study)