Is morphine an effective analgesic for procedural pain in infants?
| ISRCTN | ISRCTN82342359 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN82342359 |
| EudraCT/CTIS number | 2014-003237-25 |
| Secondary identifying numbers | 19317 |
- Submission date
- 29/07/2015
- Registration date
- 29/07/2015
- Last edited
- 18/08/2023
- Recruitment status
- Stopped
- Overall study status
- Stopped
- Condition category
- Signs and Symptoms
Plain English summary of protocol
Background and study aims
Pain in babies has negative consequences, both immediately and in the longer term. As babies cannot describe their pain the measurement and treatment of pain is difficult and, compared to adults and older children, pain is undertreated in this group. Given that a baby requiring intensive care will experience an average of 12 painful procedures per day and, the youngest and sickest babies may experience 50 procedures per day, this is a serious clinical issue that urgently needs to be addressed. The aim of this study is to test whether morphine can provide effective pain relief in babies during invasive medical procedures. While morphine is frequently given to adults when they experience pain, it is not known whether morphine provides effective pain relief for acute pain in babies. An example of a painful procedure that is frequently and regularly performed on premature babies is an eye exam that tests for Retinopathy of Prematurity – this is a disease which if untreated can lead to permanent blindness. Although the exam is considered to be painful and can result in unstable breathing and heartbeat for up to 24 hours after the exam, the pain relief currently provided during this procedure has limited efficacy. Here, we want to see if morphine can provide effective pain relief for babies undergoing this exam.
Who can participate?
Infants that were born at less than 32 weeks gestation or with a birth weight or less than 1501g. They must be in-patients at the John Radcliffe Hospital in Oxford and be between 34-42 weeks gestational age when undergoing the test.
What does the study involve?
Participants are randomly allocated into one of two groups. Those in group 1 are given morphine during an eye exam testing for Retinopathy of Prematurity. Those in group 2 are given a placebo during the same procedure. Clinical pain assessment tools are used to measure pain experienced. Newly developed brain imaging techniques are also used to see how morphine can affect pain related brain activity.
What are the possible benefits and risks of participating?
We cannot guarantee any direct benefits. At present we don’t know whether giving a pain relieving medication (morphine) reduces the pain and discomfort caused by eye exams and blood tests. We are carrying out this study to help doctors make the right decisions about the care of preterm babies in the future. Morphine is a pain-relieving drug that is routinely used in children and adults to treat acute pain. Morphine is routinely used in the neonatal unit to sedate babies when they are ventilated, although to-date few studies have been carried out where morphine has been administered to babies to provide pain relief prior to invasive procedures. The dose of morphine (100 μg/kg) will be administered by mouth and has been approved by the neonatal pharmacist. Although morphine can have effects on breathing rate and blood pressure, a study that used twice this dose did not report any adverse side effects. We do not anticipate that the babies will experience these side effects and they will be monitored very closely by the staff on the neonatal unit
Where is the study run from?
John Radcliffe Hospital, Department of Paediatrics (UK)
When is the study starting and how long is it expected to run for?
January 2015 to March 2018
Who is funding the study?
1. National Institute for Health Research, EME (UK)
2. Wellcome Trust (UK)
Who is the main contact?
Dr Rebeccah Slater
Contact information
Public
John Radcliffe Hospital
Department of Paediatrics
University of Oxford
Level 2, Children's Hospital
Oxford
OX3 9DU
United Kingdom
Study information
| Study design | Blinded placebo-controlled parallel-group randomized clinical trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Clinical trial of an investigational medicinal product (CTIMP) |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | A blinded randomised placebo controlled trial investigating the efficacy of morphine analgesia for procedural pain in infants |
| Study acronym | POPPI: procedural pain in premature infants |
| Study objectives | The aim of this study is to test whether morphine can provide effective pain relief in babies during invasive medical procedures. |
| Ethics approval(s) | The Northampton Research Ethics Committee, 23/07/2015, ref.: 15/EM/0310 |
| Health condition(s) or problem(s) studied | Topic: Children; Subtopic: Pain |
| Intervention | As of 02/09/2016: 1: Morphine Sulphate: 10ml of the IMP will be supplied in amber glass bottle at a concentration of 200 μg/ml. This will provide a dose of 100 μg/kg which will be administered orally by sterile oral/enteral 3ml syringe. 2: Placebo (inactive solution): The placebo (inactive solution) will be supplied in identical packaging but will contain only the carrier solution. Study Entry: Single Randomisation only Initial: 1. Morphine Sulphate: 2 ml of the IMP will be supplied at a concentration of 200 µg/ml. This will provide a dose of 100 µg/kg which will be administered orally by syringe 2. Placebo (inactive solution): The placebo (inactive solution) will be supplied in identical syringes but will contain only the carrier solution Study Entry : Single Randomisation only |
| Intervention type | Other |
| Primary outcome measure | Current as of 04/02/2016: 1. Clinical pain score measured using the Premature Infant Pain Profile-revised (PIPP-R) 30 seconds after ROP screening 2. Magnitude of nociceptive-specific brain activity evoked by heel lance Previous: 1. Clinical pain score measured using the Premature Infant Pain Profile (PIPP) 1 minute after ROP screening 2. Magnitude of nociceptive-specific brain activity evoked by heel lance |
| Secondary outcome measures | Current as of 04/02/2016: 1. Clinical stability in the 6-hour and 24-hour period following the start of the clinical intervention. The clinical intervention is defined as the heel lance followed by rhe ROP screening. 2. Premature infant pain profile-revised (PIPP-R) score and amplitude of nociceptive reflex withdrawal activity following heel lance 3. Drug safety will be assessed by calculating the number of incidences of apnoea that require intervention using NeoPuff or ‘bag and mask’ and the number of incidences of hypotension that require treatment with inotropes in the 24-hour period following the administration of the IMP or placebo.following ROP screening Previous: 1. Clinical stability in the 6-hour and 24-hour period after ROP screening 2. Premature infant pain profile (PIPP) score and amplitude of nociceptive reflex withdrawal activity following heel lance 3. Drug safety will be assessed by calculating the number of incidences of apnoea that require intervention using NeoPuff or ‘bag and mask’ and the number of incidences of hypotension that require treatment with inotropes in the 24-hour period following ROP screening |
| Overall study start date | 01/01/2015 |
| Completion date | 15/03/2018 |
| Reason abandoned (if study stopped) | Objectives no longer viable |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Child |
| Lower age limit | 34 Weeks |
| Upper age limit | 42 Weeks |
| Sex | Both |
| Target number of participants | Planned Sample Size: 156; UK Sample Size: 156 |
| Total final enrolment | 31 |
| Key inclusion criteria | 1. Participants will be in-patients on the neonatal unit at the John Radcliffe Hospital, Oxford 2. Infants born less than 32 weeks’ gestation or birth weight <1501 g 3. At the time of study, infants will be between 34 and 42 weeks gestational age (GA) and will be studied if they require a clinical heel lance and retinopathy of prematurity (ROP) screening on the same test occasion. We will study infants during a single ROP examination when they are greater than or equal to 34 weeks’ gestation 4. Infants for whom parents/guardians have consented to inclusion in the trial.; Upper Age Limit 42 weeks Lower Age Limit 34 weeks 5. Senior clinician considers inclusion in trial to be medically appropriate (added 04/02/2016) |
| Key exclusion criteria | 1. Intraventricular haemorrhage > grade II 2. Short bowel syndrome 3. Receiving nil by mouth due to documented gut pathology 4. Received opiates in the last 72 hours 5. Received other analgesics or sedatives in the last 24 hours 6. Previously documented episode of morphine sensitivity 7. Congenital malformation or genetic condition known to affect neurological development 8. Senior clinician considers inclusion in trial to be medically appropriate 9. Born to mothers who regularly use opiates during pregnancy or while breastfeeding or expressing breast milk |
| Date of first enrolment | 01/09/2016 |
| Date of final enrolment | 13/12/2017 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
University of Oxford
Level 2, Children's Hospital
Oxford
OX3 9DU
United Kingdom
Sponsor information
Hospital/treatment centre
Joint Research Office
Churchill Hospital
Oxford
OX3 7LE
England
United Kingdom
"ROR" |
https://ror.org/052gg0110 |
|---|
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
Private sector organisation / International organizations
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 01/11/2019 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | The plan to publish the results of the study in a peer-reviewed medical journal after we have acquired and analysed the data. |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 15/11/2016 | Yes | No | |
| Results article | results | 15/12/2018 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No | ||
| Results article | 01/08/2019 | 18/08/2023 | Yes | No |
Editorial Notes
18/08/2023: Publication reference and total final enrolment added. The study was stopped for safety reasons.
11/12/2018: The following changes were made to the trial record:
1. The recruitment end date was changed from 01/06/2019 to 13/12/2017.
2. Publication reference added.
26/10/2018: The following changes have been made to the trial record:
1. The overall trial end date has been changed from 01/11/2019 to 15/03/2018
2. The plain English summary has been updated to reflect the new trial end date
02/09/2016: Interventions have been amended (see changes in interventions field). Overall study end date has changed from 01/06/2019 to 01/11/2019. Recruitment start date has changed from 01/05/2016 to 01/09/2016. Recruitment end date has changed from 01/07/2018 to 01/06/2019. Intention to publish date changed from 31/10/2019 to 01/11/2019.
04/02/2016: Please note that as of 04/02/2016 this trial record was extensively amended. Most of the changes to this record can be found in the relevant field, under the date on which the amendment was made. The following changes have also taken place:
1. The overall end date was changed from 01/07/2018 to 01/06/2019
2. The recruitment start date was changed from 01/10/2015 to 01/05/2016 and the recruitment end date was changed from 01/07/2018 to 01/02/2019
3. The funder name was changed from "National Institute for Health Research" to "National Institute for Health Research, EME"
4. Date of ethics approval was added.
5. Expected date of publication was added
