Postoperative AnalgesiaPhase 3NCT05390905
A Clinical Trial Evaluating the Efficacy and Safety of HSK21542 in Patients for Postoperative Pain Treatment
A Phase 3 study testing HSK21542 Injection and Tramadol hydrochloride in people with Postoperative Analgesia, run by Haisco Pharmaceutical Group Co., Ltd. at 1 site in China.
Trial summary
This is a multi-center, randomized, double-blind, placebo/active-controlled study. About 387 subjects undergoing elective abdominal operation under general anesthesia are planned to be enrolled and randomized into the HSK21542 group (129 subjects), tramadol group (129 subjects), and placebo group (129 subjects). Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Postoperative Analgesia
- What is being tested?
- HSK21542 Injection and Tramadol hydrochloride
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 387 participants
- Where
- 1 siteChina
- Study dates
- 8 Jun 2022to 28 Mar 2023
- Phase
- Phase 3
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18 ≤ age ≤ 70 years old, male or female;
- The American Society of Anesthesiologists (ASA) Class I-II;
- 18 kg/m2 ≤ BMI (body mass index) ≤ 40 kg/m2;
- Subjects undergoing elective abdominal operation under general anesthesia (including laparoscopic surgery);
- Subjects with an NRS score ≥ 4 at rest within 4 h after the surgery (when the last stitch of suture is completed) determined by investigators;
- Subjects who agree to participate in this trial and voluntarily sign the informed consent form.
Who cannot join
- Previous and concomitant diseases
- 1. Subjects with a history or evidence of any of the following diseases before screening:
- History of cardiovascular diseases: uncontrolled hypertension (systolic blood pressure [SBP] ≥ 170 mmHg and/or diastolic blood pressure [DBP] ≥ 105 mmHg without treatment, or SBP > 160 mmHg and/or DBP > 100 mmHg despite antihypertensive treatment), aneurysm, serious arrhythmia, heart failure, Adams-stokes syndrome, the New York Heart Association (NYHA) Class ≥ III, serious superior vena cava syndrome, serious pericardial effusion, acute myocardial ischemia, unstable angina, myocardial infarction within 6 months before screening, history of tachycardia/bradycardia requiring medical treatment, II-III degree atrioventricular block (excluding subjects with pacemakers);
- History of respiratory system disorders: serious chronic obstructive pulmonary disease, acute exacerbation of chronic obstructive pulmonary disease, serious airway stenosis, throat mass, history of tracheoesophageal fistula or airway tear, serious respiratory infection within 2 weeks before screening;
- History of neurologic and psychiatric disorders: craniocerebral injury, convulsions, intracranial hypertension, cerebral aneurysms, history of cerebrovascular accidents; schizophrenia, mania, insanity, long-term use of psychotropic drugs, and history of cognitive dysfunction; history of depression, anxiety, and epilepsy, etc.;
- History of acute poisoning with alcohol, hypnotics, analgesics, or other central nervous system acting drugs;
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- History of any major surgery within 3 months before screening, which may affect postoperative pain assessment as judged by investigators.
- Past and concomitant medications 2. Known allergies or contraindications to opiates and other drugs that might be used in the clinical trial such as anesthetics (propofol/sevoflurane), muscle relaxants (cisatracurium), antiemetics (tropisetron); 3. Receipt of any one of the following medications or treatments at screening(with the exception of drugs specified in the protocol):
- Use of opioid and non-opioid (such as paracetamol, aspirin [daily dose > 100 mg], indometacin, diclofenac, parecoxib sodium, and other non-steroidal anti-inflammatory drugs) analgesics with the interval between the last administration and randomization shorter than 5 half-lives of the drug or the duration of response (whichever is longer);
- Consecutive use of opioid analgesics for any reason of more than 10 days within 3 months before screening;
- Use of drugs with unknown half-lives that affect the analgesic effects within 14 days before randomization, or use of drugs that affect the analgesic effects with the interval between the last administration and randomization within 5 half-lives or duration of drug effect (calculated at maximum) (as per the packaging insert); such drugs include but are not limited to: sedative hypnotics (benzodiazepines [triazolam, diazepam, midazolam, etc.], non-benzodiazepines [zolpidem, zopiclone, zaleplon, etc.]), sedative anesthetics (anesthetic ether, nitrous oxide, sodium thiopental, ketamine, etomidate, etc.), glucocorticoids (dexamethasone hydrochloride, methylprednisolone, etc.), antiepileptics (carbamazepine, sodium valproate, etc.), anxiolytics (chlordiazepoxide, diazepam, etc.), antidepressants (imipramine, amitriptyline, etc.), and Chinese herbal medicines or Chinese patent medicines that may affect efficacy evaluation as judged by investigators;
- Use of diuretics and compound drugs containing diuretics with the interval between the last administration and randomization shorter than 5 half-lives of the drug or the duration of response (whichever is longer).
- Laboratory and other tests 4. The laboratory test parameters measured at screening reach one of the following criteria:
- White blood cell count < 3.0 x 109/L;
- Platelet count < 80 x 109/L;
- Hemoglobin < 70 g/L;
- Prolongation of prothrombin time (PT) exceeding the upper limit of normal (ULN) for 3 seconds;
- Prolongation of activated partial thromboplastin time (APTT) exceeding the ULN for 10 seconds;
- Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 2 x ULN;
- Total bilirubin > 1.5 x ULN;
- Blood creatinine > 1.5 x ULN;
- Fasting blood glucose ≥ 11.1 mmol/L; 5. Positive for hepatitis C antibody (HCVAb), syphilis antibody, or human immunodeficiency virus (HIV) antibody at screening; Other circumstances 6. History of medication abuse, drug abuse, or alcohol abuse within 3 months before screening (alcohol abuse is defined as average daily alcohol drinking > 2 units of alcohol [1 unit = 360 mL of beer with 5% alcohol, 45 mL of liquor with 40% alcohol, or 150 mL of wine]); 7. History of blood donation or blood loss of ≥ 400 mL within 3 months before screening; 8. Participation in other clinical trials within 3 months before screening (defined as the receipt of investigational product or placebo); 9. Pregnant or breastfeeding females; females of child-bearing potential or males who are reluctant to use contraception during the trial; or subjects who are planning pregnancy within 3 months after the completion of the trial (including male subjects); 10. Subjects judged by investigators to have any other factors unsuitable for participating in the study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Multi-Center, Randomized, Double-Blind, Placebo/Active-Controlled Phase III Clinical Study to Evaluate the Efficacy and Safety of HSK21542 Injection for Postoperative Pain Treatment
This is a multi-center, randomized, double-blind, placebo/active-controlled study. About 387 subjects undergoing elective abdominal operation under general anesthesia are planned to be enrolled and randomized into the HSK21542 group (129 subjects), tramadol group (129 subjects), and placebo group (129 subjects).
- Conditions
- Postoperative Analgesia
- Being tested
- HSK21542 Injection, Tramadol hydrochloride, placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HSK21542 InjectionDrug
Also called HSK21542
1μg/kg/dose
Tramadol hydrochlorideDrug
Also called Tramadol
50mg/dose
placeboDrug
placebo
| Study group | Role | What they receive |
|---|---|---|
| HSK21542 | Experimental | HSK21542 injection Receives: Drug: HSK21542 Injection |
| tramadol | Experimental | Tramadol hydrochloride injection Receives: Drug: Tramadol hydrochloride |
| placebo | Placebo comparator | placebo Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sum of Pain Intensity Differences (SPID) in the HSK21542 group and the placebo group
Time-weighted SPID at rest within 0-24 h after the first administration in the HSK21542 group and the placebo group
Measured: From administration until 24 hours after administration
Sum of Pain Intensity Differences (SPID) in tramadol group and the placebo group
Time-weighted SPID at rest within 0-24 h after the first administration in the tramadol group and the placebo group
Measured: From administration until 24 hours after administration
Sum of Pain Intensity Differences (SPID) in the HSK21542 group and the tramadol group
Time-weighted SPID at rest within 0-24 h after the first administration in the HSK21542 group and the tramadol group
Measured: From administration until 24 hours after administration
Secondary outcomes (9)
Use of remedial analgesics within 0-12 h
Cumulative used amount of remedial analgesics within 0-12 h after the first administration, percentage of subjects not using remedial analgesics, and start time of remedial analgesic use
Measured: From administration until 12 hours after administration
Use of remedial analgesics within 0-24 h
Cumulative used amount of remedial analgesics within 0-24 h after the first administration, percentage of subjects not using remedial analgesics, and start time of remedial analgesic use
Measured: From administration until 24 hours after administration
Sum of Pain Intensity Differences (SPID) in each group
Time-weighted SPID at rest within 0-12 h after the first administration
Measured: From administration until 12 hours after administration
Pain intensity difference (PID)
The PID at rest at each scoring time point after the first administration
Measured: From administration until 24 hours after administration
Numerical rating scale（NRS）in each group
The NRS score at each scoring time point after the first administration
Measured: From administration until 24 hours after administration
Numerical rating scale（NRS）at 0-12 h
The ratio of subjects with NRS score ≤ 3 for resting pain at 0-12 h after the first administration
Measured: From administration until 12 hours after administration
Numerical rating scale（NRS）at 0-24 h
The ratio of subjects with NRS score ≤ 3 for resting pain at 0-24 h after the first administration
Measured: From administration until 24 hours after administration
Duration of analgesia after the first administration
duration of NRS score ≤ 3 within 24 h after the first postoperative administration or the sum of the duration of NRS score ≤ 3 with fluctuations in pain within 24 h
Measured: From administration until 24 hours after administration
Satisfaction scores on postoperative analgesia
Subject satisfaction score and investigator satisfaction score on postoperative analgesia at 24 h after the first administration
Measured: From administration until 24 hours after administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2022
- Study start8 Jun 2022
- Primary completion16 Dec 2022
- Study completion28 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Postoperative AnalgesiaStudies of the same condition, open and under way.
- More trials run by Haisco Pharmaceutical Group Co., Ltd.The sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 387 participants (actual)
Sponsor and investigators
- Lead sponsor
- Haisco Pharmaceutical Group Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05390905
- Sponsor's protocol ID
- HSK21542-303
- Status last verified
- Apr 2023
- First submitted
- 12 May 2022
- Last updated
- 4 Apr 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Yu S, Zou L, Dong S, Wu J, Huang X, Zhong Y, Wang H, Yao Y, Yan M. HSK21542 for Postoperative Analgesia in Gynecological Surgery: A Pooled Post-Hoc Analysis of Two Phase III Randomized Controlled Trials. Anesth Analg. 2026 Oct 1;143(4):869-876. doi: 10.1213/ANE.0000000000008004. Epub 2026 Mar 23.
PubMed 41874970Zhong Y, Xu Y, Lei Q, Yang M, Wang S, Hu X, Xie H, Li Y, Qin Z, Gu Z, Zhang J, Wang Y, Wu J, Wang H, Ming Y, Xia Z, Zhai H, Jiang K, Zhang P, Wang Z, Wang L, Li L, Cheng Z, Jiang H, Wang G, Chen J, Zhao Z, Chen X, Yan M. HSK21542 in patients with postoperative pain: two phase 3, multicentre, double-blind, randomized, controlled trials. Nat Commun. 2025 May 24;16(1):4830. doi: 10.1038/s41467-025-60013-y.
PubMed 40413233
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-Center, Randomized, Double-Blind, Placebo/Active-Controlled Phase III Clinical Study to Evaluate the Efficacy and Safety of HSK21542 Injection for Postoperative Pain Treatment
- ClinicalTrials.gov ID
- NCT05390905
- Acronym / sponsor ID
- HSK21542-303
- Conditions
- Postoperative Analgesia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 387 participants (actual)
- Lead sponsor
- Haisco Pharmaceutical Group Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- 8 Jun 2022 (actual)
- Primary completion
- 16 Dec 2022 (actual)
- Study completion
- 28 Mar 2023 (actual)
- First posted
- 25 May 2022 (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.
This is a multi-center, randomized, double-blind, placebo/active-controlled study. About 387 subjects undergoing elective abdominal operation under general anesthesia are planned to be enrolled and randomized into the HSK21542 group (129 subjects), tramadol group (129 subjects), and placebo group (129 subjects).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| HSK21542 | Experimental | Drug: HSK21542 InjectionHSK21542 injection |
| tramadol | Experimental | Drug: Tramadol hydrochlorideTramadol hydrochloride injection |
| placebo | Placebo comparator | Drug: placeboplacebo |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 18 ≤ age ≤ 70 years old, male or female;
- The American Society of Anesthesiologists (ASA) Class I-II;
- 18 kg/m2 ≤ BMI (body mass index) ≤ 40 kg/m2;
- Subjects undergoing elective abdominal operation under general anesthesia (including laparoscopic surgery);
- Subjects with an NRS score ≥ 4 at rest within 4 h after the surgery (when the last stitch of suture is completed) determined by investigators;
Key exclusion criteria (22 listed)
- Previous and concomitant diseases
- 1. Subjects with a history or evidence of any of the following diseases before screening:
- History of cardiovascular diseases: uncontrolled hypertension (systolic blood pressure [SBP] ≥ 170 mmHg and/or diastolic blood pressure [DBP] ≥ 105 mmHg without treatment, or SBP > 160 mmHg and/or DBP > 100 mmHg despite antihypertensive treatment), aneurysm, serious arrhythmia, heart failure, Adams-stokes syndrome, the New York Heart Association (NYHA) Class ≥ III, serious superior vena cava syndrome, serious pericardial effusion, acute myocardial ischemia, unstable angina, myocardial infarction within 6 months before screening, history of tachycardia/bradycardia requiring medical treatment, II-III degree atrioventricular block (excluding subjects with pacemakers);
- History of respiratory system disorders: serious chronic obstructive pulmonary disease, acute exacerbation of chronic obstructive pulmonary disease, serious airway stenosis, throat mass, history of tracheoesophageal fistula or airway tear, serious respiratory infection within 2 weeks before screening;
- History of neurologic and psychiatric disorders: craniocerebral injury, convulsions, intracranial hypertension, cerebral aneurysms, history of cerebrovascular accidents; schizophrenia, mania, insanity, long-term use of psychotropic drugs, and history of cognitive dysfunction; history of depression, anxiety, and epilepsy, etc.;
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 |
|---|---|---|
| HSK21542 InjectionAlso: HSK215421μg/kg/dose | Drug | HSK21542 |
| Tramadol hydrochlorideAlso: Tramadol50mg/dose | Drug | tramadol |
| placeboplacebo | Drug | placebo |
Primary outcome
Sum of Pain Intensity Differences (SPID) in the HSK21542 group and the placebo group
Time frame: From administration until 24 hours after administration
Time-weighted SPID at rest within 0-24 h after the first administration in the HSK21542 group and the placebo group
Sum of Pain Intensity Differences (SPID) in tramadol group and the placebo group
Time frame: From administration until 24 hours after administration
Time-weighted SPID at rest within 0-24 h after the first administration in the tramadol group and the placebo group
Sum of Pain Intensity Differences (SPID) in the HSK21542 group and the tramadol group
Time frame: From administration until 24 hours after administration
Time-weighted SPID at rest within 0-24 h after the first administration in the HSK21542 group and the tramadol group
9 secondary outcomes
Use of remedial analgesics within 0-12 h
Time frame: From administration until 12 hours after administration
Use of remedial analgesics within 0-24 h
Time frame: From administration until 24 hours after administration
Sum of Pain Intensity Differences (SPID) in each group
Time frame: From administration until 12 hours after administration
Pain intensity difference (PID)
Time frame: From administration until 24 hours after administration
Numerical rating scale（NRS）in each group
Time frame: From administration until 24 hours after administration
Numerical rating scale（NRS）at 0-12 h
Time frame: From administration until 12 hours after administration
Numerical rating scale（NRS）at 0-24 h
Time frame: From administration until 24 hours after administration
Duration of analgesia after the first administration
Time frame: From administration until 24 hours after administration
Satisfaction scores on postoperative analgesia
Time frame: From administration until 24 hours after administration
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 4 Apr 2023.
- Derived from this study: PubMed 41874970Yu S, Zou L, Dong S, Wu J, Huang X, Zhong Y, Wang H, Yao Y, Yan M. HSK21542 for Postoperative Analgesia in Gynecological Surgery: A Pooled Post-Hoc Analysis of Two Phase III Randomized Controlled Trials. Anesth Analg. 2026 Oct 1;143(4):869-876. doi: 10.1213/ANE.0000000000008004. Epub 2026 Mar 23.
- Derived from this study: PubMed 40413233Zhong Y, Xu Y, Lei Q, Yang M, Wang S, Hu X, Xie H, Li Y, Qin Z, Gu Z, Zhang J, Wang Y, Wu J, Wang H, Ming Y, Xia Z, Zhai H, Jiang K, Zhang P, Wang Z, Wang L, Li L, Cheng Z, Jiang H, Wang G, Chen J, Zhao Z, Chen X, Yan M. HSK21542 in patients with postoperative pain: two phase 3, multicentre, double-blind, randomized, controlled trials. Nat Commun. 2025 May 24;16(1):4830. doi: 10.1038/s41467-025-60013-y.
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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.
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 3 study testing HSK21542 Injection and Tramadol hydrochloride in people with Postoperative Analgesia, run by Haisco Pharmaceutical Group Co., Ltd. at 1 site in China.
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 6 inclusion and 22 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 4 Apr 2023. 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 China. 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 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?
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?
Sum of Pain Intensity Differences (SPID) in the HSK21542 group and the placebo group (time frame: From administration until 24 hours after administration). The study lists 3 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 NCT05390905, which also lists 2 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 4 Apr 2023.