Renal Colic
Conditions
Keywords
morphine, Pramipexole, Renal Colic, Kidney Stone, opioids, analgesia, pain relief
Brief summary
Opioid analgesics are among the most commonly prescribed class of medications in the US. While opioids may effectively control pain and other sensory disorders under acute conditions, the rates of misuse/abuse and accidental overdose have reached epidemic proportions. Clinicians are being challenged to find alternatives to opioid analgesics, or to reduce their use in treating pain whenever possible. Pre-clinical studies have shown that combining morphine (opioid drug) with pramipexole (dopamine 3 receptor agonist with some D2/D4 action) provides superior analgesia against painful stimuli than morphine alone. This analgesia is maintained even when the dose of morphine is lowered to a dose that is not effective on its own. A recent case report describes the use of this combination to restore pain control in a patient with restless legs syndrome, for which opioids alone have lost their effectiveness (Happe S, Clemens S and Brewer KL, In Review). This application proposes to establish a new therapeutic approach for treatment of a pain associated with renal colic (a common painful condition) using a novel combination of 2 existing, FDA-approved drugs. The immediate goal is to demonstrate that this drug combination can provide similar analgesia to opioid alone, and that analgesia is maintained when the opioid dose is reduced by 50%.
Detailed description
This is a double-blinded randomized controlled trial to take place in the Vidant Medical Center (VMC) Emergency Department (ED). A convenience sample of 96 participants will be drawn from patients presenting to the ED presentation with pain associated with suspected renal colic who do not experience pain relief after initial treatment with nonsteroidal anti-inflammatories. Written informed consent will be sought by a study team member after screening to ensure all inclusion criteria and no exclusion criteria are met. Once a patient has consented, they will be randomized into 1 of 2 study arms: Arm 1 (Control arm) = 0.1mg/kg of intravenous morphine + placebo pill, single dose Arm 2 (Study arm) = 0.05mg/kg intravenous morphine + 0.25mg pramipexole, single dose. Both arms include a maximum dose of 10mg/kg for the IV morphine. Pain scores will be obtained prior to administration of study drugs, and at 15-minute intervals (+/- 2 mins) after treatment for up to 2 hours, or discharge from the ED. Subjective response to each drug treatment will also be assessed every 15 minutes (+/- 2 mins) after treatment for up to 2 hours, or discharge from ED. Morphine will have a max dose of 10mg IV.
Interventions
DRUGPramipexole
Establish proof of concept that low dose morphine in combination with pramipexole is non-inferior to standard dose morphine with respect to providing analgesia in patients presenting to the ED with pain associated with renal colic.
DRUGMorphine
Establish proof of concept that low dose morphine in combination with pramipexole is non-inferior to standard dose morphine with respect to providing analgesia in patients presenting to the ED with pain associated with renal colic.
DRUGPlacebo oral tablet
Establish proof of concept that low dose morphine in combination with pramipexole is non-inferior to standard dose morphine with respect to providing analgesia in patients presenting to the ED with pain associated with renal colic.
Sponsors
East Carolina University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Participant and study team (i.e. investigators responsible for collecting pain scores) will be blinded as to treatment arm for the duration of the study (2 hours after initiation or until ED discharge/hospital admission). Treatment team (physicians and nurses involved in ED care of the patient) will be unblinded to maintain participant safety and proper medication administration. While the treating physician may be aware of what drugs have been ordered, the need for rescue medications is based on patient pain score at the 30-minute point.
Eligibility
Sex/Gender
ALL
Age
19 Years to 66 Years
Healthy volunteers
No
Inclusion criteria
* Age 19 - 65 * ED presentation with pain associated with suspected renal colic * Patient reported failure to achieve pain relief with NSAID treatment in ED (additional pain treatment needed per treatment team)
Exclusion criteria
* Age \< 19 or ≥ 66 * Allergy to any study medication * Known pregnancy or breastfeeding * Received opioid prior to enrollment * Received IV Lidocaine during current ED visit * Known chronic renal disease * Currently taking any dopamine receptor agonist or antagonists (Do I need to list?) * Unable to consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients who have an effective analgesic response (defined as at least a 50% improvement in pain scores) at 120 minutes post-randomization. | 120 minutes | Pain scores used are the numerical rating scale (0 low to 10 high) or visual analogue scale (0 low to 100mm high). |
| Total dose of opioid received at 120 minutes in patients reporting a reduction in pain scores from baseline. | 120 minutes | Dose of opioid measured in mg/kg |
| Proportion of patients who require rescue medications at 30 minutes post-randomization. | 30 minutes | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to reach effective pain reduction (defined as at least a 50% improvement in pain scores) within 120 minutes of treatment. | 120 minutes | Pain scores used are the numerical rating scale (0 low to 10 high) or visual analogue scale (0 low to 100mm high). |
| Subjective effects of the drugs measured by scores on the drug effects questionnaire. | 120 minutes | Drug effects questionnaire rates symptoms from 'not at all' at 0mm to 'extremely' at 100mm. |
Countries
United States
Outcome results
None listed