Chronic Pain Post-ProceduralPhase 4NCT03451695
Effect of Intrathecal Morphine on Chronic Pain After Elective Caesarean Section
A Phase 4 study testing Morphine in people with Chronic Pain Post-Procedural, run by B.P. Koirala Institute of Health Sciences at 1 site in Nepal.
Trial summary
The incidence of chronic post-surgical pain (CPSP) after caesarean section (CS) is reported to be as high as 18%, reflecting it to be a significant clinical problem. Studies related to prevention of progression of acute post-CS pain to its chronicity are sparse. Read more about this study
- Who is it for?
- Ages 18 to 40 years, women only
- Conditions the study is for
- Chronic Pain Post-Procedural
- What is being tested?
- Morphine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 290 participants
- Where
- 1 siteNepal
- Study dates
- 1 Apr 2018to 30 Mar 2021
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Woman in American Society of Anesthesiologists (ASA) physical status classification II with full-term singleton pregnancy undergoing planned CS under spinal anesthesia.
Who cannot join
- contraindication to spinal anaesthesia, height<150 cm, ASA > II, BMI> 40, allergy to any drug used in the study, recent opioid exposure, substance abuse, significant cardiovascular, renal, or hepatic disease; and known fetal abnormalities.
Trial locations and contacts
1 site in 1 country.
Nepal1 site
BP Koirala Institute of Health Sciences (BPKIHS)
Dharān, Koshi, 56700
About this study
Official title: Effect of Intrathecal Morphine on Chronic Pain After Elective Caesarean Section: A Randomized Controlled Trial.
The incidence of chronic post-surgical pain (CPSP) after caesarean section (CS) is reported to be as high as 18%, reflecting it to be a significant clinical problem. Studies related to prevention of progression of acute post-CS pain to its chronicity are sparse. Current guidelines on post-CS analgesia recommend the use of intrathecal (IT) opioids to spinal anaesthesia for improved post-CS pain relief. Despite its frequent use, studies related to the IT morphine use and its association with post-CS chronic pain are lacking.
A recent prospective observation study revealed a significant reduction in persistent pain after CS when IT morphine was used as an adjuvant to spinal anaesthesia. However, there is no any randomized controlled trial (RCT) that has explored this association to date. We hypothesized that spinal morphine would reduce the incidence of persistent pain after CS.
Read the detailed description
This prospective, randomised, double-blind trial will take place at B.P Koirala Institute of Health Sciences, a University hospital situated in Nepal. Approval for the study has been obtained from the institution ethical committee. After the trial is registered, recruitment of the patient will be initiated. Consent for the participation in the study will be obtained during pre-anaesthetic assessment visits in the evening before surgery. During this visit, preoperative anxiety level (hospital anxiety and depression scale), pain catastrophizing (assessed with pain catastrophizing scale), preoperative pain sensitivity (assessed with pain pressure threshold and tolerance) will be recorded. The investigator will also educate the patients regarding the use of NRS scores for postoperative pain and satisfaction ratings.
Patients will be randomly assigned in a 1:1 ratio to one of the two groups (morphine and placebo groups). Randomization will be done in variable block sizes (4/6/8) by an internet based random-number generator list.
Morphine group will receive intrathecal 11 mg of hyperbaric bupivacaine (2.2 mL 0.5%), 10μg of fentanyl (0.2 ml) and 100 μg of preservative free morphine (0.1 ml). Placebo group will receive 11 mg of hyperbaric bupivacaine (2.2 mL 0.5%), 10μg of fentanyl (0.2 ml) and normal saline (0.1ml).
Postoperatively, pain, opioid consumption, sedation, nausea or vomiting, pruritus, and respiratory depression in the postanesthesia care unit (time 0 hours) and at 2, 6, 12, 24, and 48 hours will be evaluated. The area of hyperalgesia around the surgical incision will be assessed at 48 hrs postoperatively using a von Frey filament.
Patient satisfaction from postoperative analgesia will be assessed using a 5-point scale (1 = very unsatisfied, 2 = unsatisfied, 3 = fair, 4 = satisfied and 5 = very satisfied). At 8 wks patients will be assessed for post-natal depression using Edinburgh postnatal depression scale.
Patients will be contacted by telephone by one of the blinded investigator at 3, 6 months after the surgery. The short form brief pain inventory will be used to determine post-CS chronic pain
- Conditions
- Chronic Pain Post-Procedural
- Being tested
- Morphine, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MorphineDrug
Morphine group will receive intrathecal 11 mg of hyperbaric bupivacaine (2.2 mL 0.5%), 10 μg of fentanyl (0.2 ml) and 100 μg of preservative free morphine (0.1 ml).
PlaceboDrug
Placebo group will receive 11 mg of hyperbaric bupivacaine (2.2 mL 0.5%), 10 μg of fentanyl (0.2 ml) and normal saline (0.1ml)
| Study group | Role | What they receive |
|---|---|---|
| Morphine group | Experimental | Morphine group will receive intrathecal 11 mg of hyperbaric bupivacaine (2.2 mL 0.5%), 10 μg of fentanyl (0.2 ml) and 100 μg of preservative free morphine (0.1 ml). Receives: Drug: Morphine |
| Placebo group | Placebo comparator | Placebo group will receive intrathecal 11 mg of hyperbaric bupivacaine (2.2 mL 0.5%), 10 μg of fentanyl (0.2 ml) and normal saline (0.1 ml). Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with the incidence of post surgery chronic pain at 3 months following elective caesarean section
To find the number of participants with the incidence of post surgery chronic pain at 3 months following elective caesarean section in those receiving Intrathecal morphine and normal saline
Measured: 3 months after elective caesarean section
Secondary outcomes (5)
Number of participants with the incidence of post surgery chronic pain at 6 months following elective caesarean section
To find the number of participants with the incidence of post surgery chronic pain at 6 months following elective caesarean section in those receiving Intrathecal morphine and normal saline
Measured: 6 month after elective caesarean section
Brief pain inventory (BPI) pain severity scores at 3 and 6 month after elective caesarean section between those receiving intrathecal morphine and normal saline
Short form Brief pain inventory (BPI) pain severity scores: Pain is rated on a 0 to 10 numerical rating scale, with 0="no pain" or and 10=pain "as bad as you can imagine." Participants rate their worst, least, and average pain over the last seven days, as well as their pain right now.
Measured: 3 and 6 months after elective caesarean section
Brief Pain Inventory (BPI) pain interference scores at 3 and 6 month after elective caesarean section between those receiving intrathecal morphine and normal saline
Short form Brief pain inventory (BPI) pain interference scores: Participants rate how much pain interfered with various daily activities, including general activity, walking, work, mood, enjoyment of life, relations with others, and sleep. The interference items is presented with 0-10 scales, with 0=no interference and 10=interferes completely.
Measured: 3 and 6 months after elective caesarean section
Any pain medication or treatment received for relieving pain. If so, the amount of pain relieved.
Currently use of pain medications, its dosages or any other treatment will be recorded.In the last 24 hours, how much relief have pain treatment or medications provided. Please rate in 0-100% where 0% is no relief, 100% complete relief.
Measured: 3 and 6 months after elective caesarean section
Numerical rating Scale (NRS) pain scores and opioid consumption post operatively
Post operative pain intensity will be assessed using Numerical rating scale(NRS), where 0="no pain" or and 10=pain "as bad as you can imagine." Total opioid consumption will be calculated as total morphine or equivalent in mg.
Measured: 24 and 48 hrs after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2018
- Study start1 Apr 2018
- Primary completion26 Dec 2020
- Study completion30 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Pain Post-ProceduralStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 290 participants (actual)
Sponsor and investigators
- Lead sponsor
- B.P. Koirala Institute of Health Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr Asish Subedi, B.P. Koirala Institute of Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03451695
- Sponsor's protocol ID
- IRC/1183/017
- Status last verified
- Apr 2021
- First submitted
- 20 Feb 2018
- Last updated
- 6 Apr 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The final research data will be stored in Mendeley. The final data will be released and shared during the publication process of the manuscript.
Publications
Subedi A, Schyns-van den Berg AMJV, Thapa P, Limbu PM, Trikhatri Y, Poudel A, Dhakal Y, Bhandari S. Intrathecal morphine does not prevent chronic postsurgical pain after elective Caesarean delivery: a randomised controlled trial. Br J Anaesth. 2022 Apr;128(4):700-707. doi: 10.1016/j.bja.2021.11.036. Epub 2022 Jan 26.
PubMed 35090722
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Intrathecal Morphine on Chronic Pain After Elective Caesarean Section: A Randomized Controlled Trial.
- ClinicalTrials.gov ID
- NCT03451695
- Acronym / sponsor ID
- IRC/1183/017
- Conditions
- Chronic Pain Post-Procedural
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 290 participants (actual)
- Lead sponsor
- B.P. Koirala Institute of Health SciencesUniversity, hospital or other
- Study start
- 1 Apr 2018 (actual)
- Primary completion
- 26 Dec 2020 (actual)
- Study completion
- 30 Mar 2021 (actual)
- First posted
- 2 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The incidence of chronic post-surgical pain (CPSP) after caesarean section (CS) is reported to be as high as 18%, reflecting it to be a significant clinical problem. Studies related to prevention of progression of acute post-CS pain to its chronicity are sparse. Current guidelines on post-CS analgesia recommend the use of intrathecal (IT) opioids to spinal anaesthesia for improved post-CS pain relief. Despite its frequent use, studies related to the IT morphine use and its association with post-CS chronic pain are lacking.
A recent prospective observation study revealed a significant reduction in persistent pain after CS when IT morphine was used as an adjuvant to spinal anaesthesia. However, there is no any randomized controlled trial (RCT) that has explored this association to date. We hypothesized that spinal morphine would reduce the incidence of persistent pain after CS.
Detailed description
This prospective, randomised, double-blind trial will take place at B.P Koirala Institute of Health Sciences, a University hospital situated in Nepal. Approval for the study has been obtained from the institution ethical committee. After the trial is registered, recruitment of the patient will be initiated. Consent for the participation in the study will be obtained during pre-anaesthetic assessment visits in the evening before surgery. During this visit, preoperative anxiety level (hospital anxiety and depression scale), pain catastrophizing (assessed with pain catastrophizing scale), preoperative pain sensitivity (assessed with pain pressure threshold and tolerance) will be recorded. The investigator will also educate the patients regarding the use of NRS scores for postoperative pain and satisfaction ratings.
Patients will be randomly assigned in a 1:1 ratio to one of the two groups (morphine and placebo groups). Randomization will be done in variable block sizes (4/6/8) by an internet based random-number generator list.
Morphine group will receive intrathecal 11 mg of hyperbaric bupivacaine (2.2 mL 0.5%), 10μg of fentanyl (0.2 ml) and 100 μg of preservative free morphine (0.1 ml). Placebo group will receive 11 mg of hyperbaric bupivacaine (2.2 mL 0.5%), 10μg of fentanyl (0.2 ml) and normal saline (0.1ml).
Postoperatively, pain, opioid consumption, sedation, nausea or vomiting, pruritus, and respiratory depression in the postanesthesia care unit (time 0 hours) and at 2, 6, 12, 24, and 48 hours will be evaluated. The area of hyperalgesia around the surgical incision will be assessed at 48 hrs postoperatively using a von Frey filament.
Patient satisfaction from postoperative analgesia will be assessed using a 5-point scale (1 = very unsatisfied, 2 = unsatisfied, 3 = fair, 4 = satisfied and 5 = very satisfied). At 8 wks patients will be assessed for post-natal depression using Edinburgh postnatal depression scale.
Patients will be contacted by telephone by one of the blinded investigator at 3, 6 months after the surgery. The short form brief pain inventory will be used to determine post-CS chronic pain
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Morphine group | Experimental | Drug: MorphineMorphine group will receive intrathecal 11 mg of hyperbaric bupivacaine (2.2 mL 0.5%), 10 μg of fentanyl (0.2 ml) and 100 μg of preservative free morphine (0.1 ml). |
| Placebo group | Placebo comparator | Drug: PlaceboPlacebo group will receive intrathecal 11 mg of hyperbaric bupivacaine (2.2 mL 0.5%), 10 μg of fentanyl (0.2 ml) and normal saline (0.1 ml). |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Woman in American Society of Anesthesiologists (ASA) physical status classification II with full-term singleton pregnancy undergoing planned CS under spinal anesthesia.
Key exclusion criteria (1 listed)
- contraindication to spinal anaesthesia, height<150 cm, ASA > II, BMI> 40, allergy to any drug used in the study, recent opioid exposure, substance abuse, significant cardiovascular, renal, or hepatic disease; and known fetal abnormalities.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MorphineMorphine group will receive intrathecal 11 mg of hyperbaric bupivacaine (2.2 mL 0.5%), 10 μg of fentanyl (0.2 ml) and 100 μg of preservative free morphine (0.1 ml). | Drug | Morphine group |
| PlaceboPlacebo group will receive 11 mg of hyperbaric bupivacaine (2.2 mL 0.5%), 10 μg of fentanyl (0.2 ml) and normal saline (0.1ml) | Drug | Placebo group |
Primary outcome
Number of participants with the incidence of post surgery chronic pain at 3 months following elective caesarean section
Time frame: 3 months after elective caesarean section
To find the number of participants with the incidence of post surgery chronic pain at 3 months following elective caesarean section in those receiving Intrathecal morphine and normal saline
5 secondary outcomes
Number of participants with the incidence of post surgery chronic pain at 6 months following elective caesarean section
Time frame: 6 month after elective caesarean section
Brief pain inventory (BPI) pain severity scores at 3 and 6 month after elective caesarean section between those receiving intrathecal morphine and normal saline
Time frame: 3 and 6 months after elective caesarean section
Brief Pain Inventory (BPI) pain interference scores at 3 and 6 month after elective caesarean section between those receiving intrathecal morphine and normal saline
Time frame: 3 and 6 months after elective caesarean section
Any pain medication or treatment received for relieving pain. If so, the amount of pain relieved.
Time frame: 3 and 6 months after elective caesarean section
Numerical rating Scale (NRS) pain scores and opioid consumption post operatively
Time frame: 24 and 48 hrs after surgery
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2021.
- Derived from this study: PubMed 35090722Subedi A, Schyns-van den Berg AMJV, Thapa P, Limbu PM, Trikhatri Y, Poudel A, Dhakal Y, Bhandari S. Intrathecal morphine does not prevent chronic postsurgical pain after elective Caesarean delivery: a randomised controlled trial. Br J Anaesth. 2022 Apr;128(4):700-707. doi: 10.1016/j.bja.2021.11.036. Epub 2022 Jan 26.
- Individual participant dataSharing planned: Yes. The final research data will be stored in Mendeley. The final data will be released and shared during the publication process of the manuscript.
Related trials for Chronic Pain Post-Procedural
RecruitingPhase 4
NonNarcotic Pain Control in Percutaneous Needle Tenotomy of Elbow
Elbow Pain, Chronic Pain
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Morphine in people with Chronic Pain Post-Procedural, run by B.P. Koirala Institute of Health Sciences at 1 site in Nepal.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Nepal. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with the incidence of post surgery chronic pain at 3 months following elective caesarean section (time frame: 3 months after elective caesarean section). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03451695, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Apr 2021.