Depression, PostpartumPhase 2/3CODEPADNCT03167905
CODEPAD (Collaborative Outcomes of DEpression and Pain Associated With Delivery)
A Phase 2/3 study testing Epidural delivery system, Entonox and Meperidine in people with Depression, Postpartum and Analgesia, Obstetrical, run by KK Women's and Children's Hospital at 1 site in Singapore.
Trial summary
Postnatal depression affects about 10-15% of women after childbirth. Approximately 3-5% of women experience a moderate-to-severe depression that requires medical attention. This study aims to investigate the implication of pain relief choice in reducing the postnatal depression of women who deliver their babies. Read more about this study
- Who is it for?
- Ages 21 to 50 years, women only
- Conditions the study is for
- Depression, Postpartum, Analgesia, Obstetrical, Anesthesia, Obstetrical
- What is being tested?
- Epidural delivery system, Entonox and Meperidine
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 881 participants
- Where
- 1 siteSingapore
- Study dates
- 15 Jun 2017to 31 Dec 2027
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
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 21 to 50 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Healthy adult (American Society of Anesthesiologists physical status 1 and 2) parturients at term (36 weeks gestation or more) (nulliparous and multiparous);
- With a singleton fetus.
Who cannot join
- Multiple pregnancies;
- Non-cephalic fetal presentation;
- Obstetric complications (e.g. pre-eclampsia, uncontrolled hypertension, uncontrolled diabetes);
- Elective and urgent caesarean section (not from delivery suite).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Comparison of the Role of Epidural Analgesia Versus Non-epidural Analgesia in Postnatal Depression and Persistent Pain Development: a Randomized Controlled Trial
Postnatal depression affects about 10-15% of women after childbirth. Approximately 3-5% of women experience a moderate-to-severe depression that requires medical attention. This study aims to investigate the implication of pain relief choice in reducing the postnatal depression of women who deliver their babies.
Read the detailed description
If the patients have not decided on which pain relief method to be used, and would like to take part in this study, they will be assigned to either epidural or non-epidural pain relief for labour based on the study randomization result. Blood samples will be drawn to study the presence of known functional polymorphisms in candidate genes associated with depression, pain, stress and anxiety. Patients will be followed up with study questionnaires related to pain and postnatal depression screening during the study. For some of the patients, a discrete choice experiment (DCE) on pain relief choice will be conducted, and their preferences on epidural analgesia will be asked.
During any time of the labour period, the patient is allowed to switch the pain relief option upon request.
- Being tested
- Epidural delivery system, Entonox, Meperidine, Ultiva, Fentanyl
- Keywords
- Anesthesia, Obstetrical, Epidural anesthesia, Postnatal depression, Persistent pain
- Medical subject headings
- Depression, Postpartum, Agnosia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Epidural delivery systemDevice
Epidural delivery system for maintenance of labour epidural analgesia using 0.1% ropivacaine (amide local anaesthetic) with 2mcg/ml fentanyl (opioid) as maintenance solution.
EntonoxDrug
Also called Laughing gas
Entonox will be given upon request in non-epidural group.
MeperidineDrug
Also called Pethidine
Intramuscular pethidine (75mg/1.5ml) will be given upon request in non-epidural group.
UltivaDrug
Also called Remifentanil
Intravenous patient controlled remifentanil (20-40mcg/ml) is only given when the patient rejects or cannot receive pethidine and entonox in non-epidural group..
FentanylDrug
Epidural delivery system for maintenance of labour epidural analgesia using 0.1% ropivacaine (amide local anaesthetic) with 2mcg/ml fentanyl (opioid) as maintenance solution.
RopivacaineDrug
Epidural delivery system for maintenance of labour epidural analgesia using 0.1% ropivacaine (amide local anaesthetic) with 2mcg/ml fentanyl (opioid) as maintenance solution.
| Study group | Role | What they receive |
|---|---|---|
| Epidural group | Experimental | Patients are assigned to receive epidural delivery system (fentanyl and ropivacaine) for labour as pain relief option. Receives: Device: Epidural delivery system; Drug: Fentanyl; Drug: Ropivacaine |
| Non-epidural group | Active comparator | Patients are assigned to receive entonox (laughing gas), meperidine (pethidine) or remifentanil (Ultiva) for labour as pain relief option. Receives: Drug: Entonox; Drug: Meperidine; Drug: Ultiva |
What is being measured
The primary outcome is the main question the study is designed to answer.
The incidence of major postnatal depression in both groups
Edinburgh Postnatal Depression Scale (EPDS) score>=13
Measured: 6-10 weeks after delivery
The incidence of (clinically significant, probable) postnatal depression in both groups
Edinburgh Postnatal Depression Scale (EPDS) score>=10
Measured: 6-10 weeks after delivery
Secondary outcomes (11)
The incidence of acquiring post-delivery persistent pain in both groups
Pain score>3 in the perineal, surgical scar or abdomen region that lasts for at least 6 weeks post-delivery
Measured: 6-10 weeks after delivery
Pain vulnerability in both groups (1)
Assessment via Pain Catastrophizing Scale (PCS) questionnaire before and after delivery
Measured: Upon recruitment until 6-10 weeks after delivery
Pain vulnerability in both groups (2)
Assessment via Central Sensitisation Inventory (CSI) questionnaire before and after delivery
Measured: Upon recruitment until 6-10 weeks after delivery
Pain vulnerability in both groups (3)
Assessment via Angle Labor Pain Questionnaire (A-LPQ) during first stage of labor when the participants experience labor pain
Measured: Upon recruitment till end of first stage of labor (1 day)
Psychological vulnerability in both groups (1)
Assessment via Fear-Avoidance Components Scale (FACS) questionnaire before delivery
Measured: Upon recruitment until 5 days after delivery
Psychological vulnerability in both groups (2)
Assessment via State Trait Anxiety Inventory (STAI) questionnaire before delivery
Measured: Upon recruitment until 5 days after delivery
Psychological vulnerability in both groups (3)
Assessment via Perceived Stress Scale (PSS) questionnaire before delivery
Measured: Upon recruitment until 5 days after delivery
Pain severity in both groups
Pain score>3 during labour
Measured: During labour till one day after delivery
Preferences for labor analgesia
Recruited patients will be administered a survey on Discrete Choice Experiment (DCE) and other questions on their preferences for labor analgesia. For DCE, nine tasks will be included in which parturients will choose one of four hypothetical forms of labor analgesia: 1) epidural analgesia, 2) pethidine, 3) Entonox (nitrous oxide-oxygen mixture), and 4) no labor analgesia, which varies with regards to six attributes: 1) pain intensity following treatment, 2) duration of second stage of labor, 3) risk of instrumental delivery, 4) risk of back pain, 5) risk of permanent nerve injury, and 6) out-of-pocket cost.
Measured: Prior to labor and delivery
Preferences for epidural analgesia
Recruited patients will be administered a survey on their preferences and opinions on epidural analgesia, including their concerns on possible risk of epidural analgesia e.g. instrumental delivery, prolonged duration of second stage of labor, back pain etc.
Measured: Prior to labor and delivery
Chinese version of Angle Labor Pain Questionnaire (A-LPQ)
Assessment via Angle Labor Pain Questionnaire (A-LPQ) during first stage of labor when the participants experience labor pain. The tool comprises 22 items divided into five subscales on the childbirth pain experience: the enormity of the pain, the fear and anxiety, uterine contraction pain, birthing pain, and the back pain/ long haul. Each item is scaled from 0 to 10, implying a range from non to worst possible or extremely (where applicable), and therefore has a total score ranged from 0 to 220. The higher the score, the greater the labor pain.
Measured: Upon recruitment till end of first stage of labor (1 day)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2017
- Study start15 Jun 2017
- Primary completion19 Jul 2021
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Depression, PostpartumStudies 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Cross over or switch to the other group of analgesia is allowed.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 881 participants (actual)
Sponsor and investigators
- Lead sponsor
- KK Women's and Children's Hospital
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Sng Ban Leong, KK Women's and Children's Hospital
- Investigators
- Ban Leong Sng, FANZCA, Principal investigator, KK Women's and Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03167905
- Sponsor's protocol ID
- 2017/2090
- Acronym
- CODEPAD
- Status last verified
- Aug 2026
- First submitted
- 2 May 2017
- Last updated
- 6 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Tan HS, Tan CW, Sultana R, Chen HY, Chua T, Rahman N, Gandhi M, Sia ATH, Sng BL. The association between epidural labour analgesia and postpartum depression: a randomised controlled trial. Anaesthesia. 2024 Apr;79(4):357-367. doi: 10.1111/anae.16178. Epub 2023 Nov 21.
PubMed 37990597Tan CW, Wang S, Sultana R, Sia ATH, Sng BL. Associations of Pain, Analgesia Technique, and Psychological Factors with Central Sensitization after Childbirth. Anaesth Crit Care Pain Med. 2026 Jun 18:101881. doi: 10.1016/j.accpm.2026.101881. Online ahead of print.
PubMed 42314868Tan CW, Liu Y, Sultana R, Sia ATH, Sng BL. Understanding maternal pain and psychological vulnerabilities associated with the development of sub-acute pain after childbirth. BMC Anesthesiol. 2026 May 7;26(1):385. doi: 10.1186/s12871-026-03885-x.
PubMed 42092800Tan CW, Sultana R, Chen HY, Chua TE, Ku CW, Sng BL. Investigating the association between pain and psychological vulnerabilities and postpartum depression. Sci Rep. 2026 Apr 28;16(1):19691. doi: 10.1038/s41598-026-50140-x.
PubMed 42049811Chan JCY, Sultana R, Mathur D, Tan CW, Sng BL. The association of pain and psychological vulnerabilities with postpartum pain catastrophizing: a secondary analysis of a randomized controlled trial. Can J Anaesth. 2025 Apr;72(4):603-614. doi: 10.1007/s12630-025-02920-8. Epub 2025 Mar 20.
PubMed 40113655Ayuby NA, Ang MQ, Sultana R, Tan CW, Sng BL. Investigating the association between labor pain and cessation of breastfeeding. Sci Rep. 2024 Dec 28;14(1):31361. doi: 10.1038/s41598-024-82850-5.
PubMed 39732915Tan CW, Tan NY, Sultana R, Tan HS, Sng BL. Investigating the association factors of acute postpartum pain: a cohort study. BMC Anesthesiol. 2023 Jul 25;23(1):252. doi: 10.1186/s12871-023-02214-w.
PubMed 37491196
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of the Role of Epidural Analgesia Versus Non-epidural Analgesia in Postnatal Depression and Persistent Pain Development: a Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT03167905
- Acronym / sponsor ID
- CODEPAD / 2017/2090
- Keywords
- Anesthesia, Obstetrical, Epidural anesthesia, Postnatal depression, Persistent pain
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 881 participants (actual)
- Lead sponsor
- KK Women's and Children's HospitalOther government
- Study start
- 15 Jun 2017 (actual)
- Primary completion
- 19 Jul 2021 (actual)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 30 May 2017 (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.
Postnatal depression affects about 10-15% of women after childbirth. Approximately 3-5% of women experience a moderate-to-severe depression that requires medical attention. This study aims to investigate the implication of pain relief choice in reducing the postnatal depression of women who deliver their babies.
Detailed description
If the patients have not decided on which pain relief method to be used, and would like to take part in this study, they will be assigned to either epidural or non-epidural pain relief for labour based on the study randomization result. Blood samples will be drawn to study the presence of known functional polymorphisms in candidate genes associated with depression, pain, stress and anxiety. Patients will be followed up with study questionnaires related to pain and postnatal depression screening during the study. For some of the patients, a discrete choice experiment (DCE) on pain relief choice will be conducted, and their preferences on epidural analgesia will be asked.
During any time of the labour period, the patient is allowed to switch the pain relief option upon request.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- Cross over or switch to the other group of analgesia is allowed.
| Arm | Type | Receives |
|---|---|---|
| Epidural group | Experimental | Device: Epidural delivery system, Drug: Fentanyl, Drug: RopivacainePatients are assigned to receive epidural delivery system (fentanyl and ropivacaine) for labour as pain relief option. |
| Non-epidural group | Active comparator | Drug: Entonox, Drug: Meperidine, Drug: UltivaPatients are assigned to receive entonox (laughing gas), meperidine (pethidine) or remifentanil (Ultiva) for labour as pain relief option. |
Who may qualify
- Ages
- 21 to 50 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Healthy adult (American Society of Anesthesiologists physical status 1 and 2) parturients at term (36 weeks gestation or more) (nulliparous and multiparous);
- With a singleton fetus.
Key exclusion criteria (4 listed)
- Multiple pregnancies;
- Non-cephalic fetal presentation;
- Obstetric complications (e.g. pre-eclampsia, uncontrolled hypertension, uncontrolled diabetes);
- Elective and urgent caesarean section (not from delivery suite).
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 |
|---|---|---|
| Epidural delivery systemEpidural delivery system for maintenance of labour epidural analgesia using 0.1% ropivacaine (amide local anaesthetic) with 2mcg/ml fentanyl (opioid) as maintenance solution. | Device | Epidural group |
| EntonoxAlso: Laughing gasEntonox will be given upon request in non-epidural group. | Drug | Non-epidural group |
| MeperidineAlso: PethidineIntramuscular pethidine (75mg/1.5ml) will be given upon request in non-epidural group. | Drug | Non-epidural group |
| UltivaAlso: RemifentanilIntravenous patient controlled remifentanil (20-40mcg/ml) is only given when the patient rejects or cannot receive pethidine and entonox in non-epidural group.. | Drug | Non-epidural group |
| FentanylEpidural delivery system for maintenance of labour epidural analgesia using 0.1% ropivacaine (amide local anaesthetic) with 2mcg/ml fentanyl (opioid) as maintenance solution. | Drug | Epidural group |
| RopivacaineEpidural delivery system for maintenance of labour epidural analgesia using 0.1% ropivacaine (amide local anaesthetic) with 2mcg/ml fentanyl (opioid) as maintenance solution. | Drug | Epidural group |
Primary outcome
The incidence of major postnatal depression in both groups
Time frame: 6-10 weeks after delivery
Edinburgh Postnatal Depression Scale (EPDS) score>=13
The incidence of (clinically significant, probable) postnatal depression in both groups
Time frame: 6-10 weeks after delivery
Edinburgh Postnatal Depression Scale (EPDS) score>=10
11 secondary outcomes
The incidence of acquiring post-delivery persistent pain in both groups
Time frame: 6-10 weeks after delivery
Pain vulnerability in both groups (1)
Time frame: Upon recruitment until 6-10 weeks after delivery
Pain vulnerability in both groups (2)
Time frame: Upon recruitment until 6-10 weeks after delivery
Pain vulnerability in both groups (3)
Time frame: Upon recruitment till end of first stage of labor (1 day)
Psychological vulnerability in both groups (1)
Time frame: Upon recruitment until 5 days after delivery
Psychological vulnerability in both groups (2)
Time frame: Upon recruitment until 5 days after delivery
Psychological vulnerability in both groups (3)
Time frame: Upon recruitment until 5 days after delivery
Pain severity in both groups
Time frame: During labour till one day after delivery
Preferences for labor analgesia
Time frame: Prior to labor and delivery
Preferences for epidural analgesia
Time frame: Prior to labor and delivery
Chinese version of Angle Labor Pain Questionnaire (A-LPQ)
Time frame: Upon recruitment till end of first stage of labor (1 day)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2026.
- Results publication: PubMed 37990597Tan HS, Tan CW, Sultana R, Chen HY, Chua T, Rahman N, Gandhi M, Sia ATH, Sng BL. The association between epidural labour analgesia and postpartum depression: a randomised controlled trial. Anaesthesia. 2024 Apr;79(4):357-367. doi: 10.1111/anae.16178. Epub 2023 Nov 21.
- Derived from this study: PubMed 42314868Tan CW, Wang S, Sultana R, Sia ATH, Sng BL. Associations of Pain, Analgesia Technique, and Psychological Factors with Central Sensitization after Childbirth. Anaesth Crit Care Pain Med. 2026 Jun 18:101881. doi: 10.1016/j.accpm.2026.101881. Online ahead of print.
- Derived from this study: PubMed 42092800Tan CW, Liu Y, Sultana R, Sia ATH, Sng BL. Understanding maternal pain and psychological vulnerabilities associated with the development of sub-acute pain after childbirth. BMC Anesthesiol. 2026 May 7;26(1):385. doi: 10.1186/s12871-026-03885-x.
- Derived from this study: PubMed 42049811Tan CW, Sultana R, Chen HY, Chua TE, Ku CW, Sng BL. Investigating the association between pain and psychological vulnerabilities and postpartum depression. Sci Rep. 2026 Apr 28;16(1):19691. doi: 10.1038/s41598-026-50140-x.
- Derived from this study: PubMed 40113655Chan JCY, Sultana R, Mathur D, Tan CW, Sng BL. The association of pain and psychological vulnerabilities with postpartum pain catastrophizing: a secondary analysis of a randomized controlled trial. Can J Anaesth. 2025 Apr;72(4):603-614. doi: 10.1007/s12630-025-02920-8. Epub 2025 Mar 20.
- Derived from this study: PubMed 39732915Ayuby NA, Ang MQ, Sultana R, Tan CW, Sng BL. Investigating the association between labor pain and cessation of breastfeeding. Sci Rep. 2024 Dec 28;14(1):31361. doi: 10.1038/s41598-024-82850-5.
- Derived from this study: PubMed 37491196Tan CW, Tan NY, Sultana R, Tan HS, Sng BL. Investigating the association factors of acute postpartum pain: a cohort study. BMC Anesthesiol. 2023 Jul 25;23(1):252. doi: 10.1186/s12871-023-02214-w.
- Published data on the primary outcome on epidural labour analgesia and postnatal depressionLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Ban Leong Sng, FANZCA principal investigator
KK Women's and Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Epidural delivery system, Entonox and Meperidine in people with Depression, Postpartum and Analgesia, Obstetrical, run by KK Women's and Children's Hospital at 1 site in Singapore.
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 2 inclusion and 4 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: under way, not looking for participants, as of the sponsor's last update on 6 Aug 2026. 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 Singapore. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
The incidence of major postnatal depression in both groups (time frame: 6-10 weeks after delivery). The study lists 2 primary outcomes in all. 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 NCT03167905, which also lists 7 linked publications.
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 Aug 2026.