Postmenopausal OsteoporosisPhase 4NCT04719481
Pravastatin Reduces Acute Phase Response of Zoledronic Acid
A Phase 4 study testing Pravastatin Sodium 80 MG in people with Postmenopausal Osteoporosis, run by Peking University Third Hospital.
Trial summary
Acute phase response (APR) is one of the most common adverse events in osteoporosis with zoledronic acid treatment. It's reported that this reaction is related to the blockade of the mevalonate pathway, leading to isopentenyl pyrophosphate (IPP) accumulation. Read more about this study
- Who is it for?
- Any age, women onlyHealthy volunteers can take part
- Conditions the study is for
- Postmenopausal Osteoporosis
- What is being tested?
- Pravastatin Sodium 80 MG
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 110 participants
- Where
- No sites listed yet
- Study dates
- Nov 2021to Apr 2022
- 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 Any age
- Women only
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Chinese Han ethnic postmenopausal women.
- Bone mineral density values of less than 2.5 standard deviations (SD) below the normal adult mean.
- Willing to participate in this study.
Who cannot join
- Prior treatment with biphosphonates (oral or intravenous).
- Fever and/or any viral or bacterial infections within 30 days prior to randomization.
- Patients with evidence of any cancer or with a history of cancer.
- Contraindication to zoledronic acid:
- Known hypersensitivity to zoledronic acid or other bisphosphonate or zoledronic acid formulation (excipients); Serum calcium level < 2.13 mmol/L (8.5 mg/dL), free serum calcium level <0.95 mmol/L (3.8 mg/dL) or untreated hypocalcemia; Childbearing or child-breastfeeding women; Creatinine clearance < 35 mL/min;
- Restrictions:
Show all 12Show fewer
- Patients currently receiving aminoglycoside, diuretics or thalidomide.
- Contraindication to pravastatin:
- Known hypersensitivity to pravastatin or other excipients in pravastatin sodium formulation.
- Restrictions:
- Patients with severe liver insufficiency, history of severe liver insufficiency, active liver disease or continuously elevated transaminase; Patients with severe renal insufficiency or history of severe renal insufficiency; Patients currently receiving fibrates (e.g., bezafibrate), immunosuppressive drug (e.g., cyclosporine) or niacin.
- Any physiological or medical condition which, in the opinion of the investigator, would preclude the participant from this trail.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: The Reduction Effect of Oral Pravastatin on Acute Phase Response of Intravenous Zoledronic Acid: a Real-world Study
Acute phase response (APR) is one of the most common adverse events in osteoporosis with zoledronic acid treatment. It's reported that this reaction is related to the blockade of the mevalonate pathway, leading to isopentenyl pyrophosphate (IPP) accumulation. And the latter can active γδT cells in the circulation, resulting in inflammatory cytokine release. Statins can inhibit the conversion of HMG-CoA to mevalonate that may reduce the accumulation of IPP. Therefore, it is possible that statins can be taken in advance to reduce APR caused by zoledronic acid infusion.
- Conditions
- Postmenopausal Osteoporosis
- Being tested
- Pravastatin Sodium 80 MG, Placebo
- Keywords
- acute phase response, zoledronic acid, pravastatin
- Medical subject headings
- Osteoporosis, Postmenopausal, Acute-Phase Reaction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pravastatin Sodium 80 MGDrug
Also called Meibailezhen
daily oral administration of 80mg
PlaceboDrug
Also called Meibailezhen placebo
daily oral administration
| Study group | Role | What they receive |
|---|---|---|
| pravastatin 80mg/d | Experimental | Oral administration of pravastatin at 1 h before zoledronic acid infusion, 24 h and 48 h after zoledronic acid infusion Receives: Drug: Pravastatin Sodium 80 MG |
| placebo | Placebo comparator | Oral administration of placebo at 1 h before zoledronic acid infusion, 24 h and 48 h after zoledronic acid infusion Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of acute phase response
Effect of oral pravastatin on the incidence of acute phase response within 72 hours after zoledronic acid infusion
Measured: 0-72 hours
Secondary outcomes (12)
Occurrence time of fever
Effect of oral pravastatin on the occurrence time of fever after zoledronic acid infusion
Measured: from 8:00 a.m. to 8:00 p.m. with interval of 4 hours in Day -2 and Day -1, from 9:00 a.m. to 9:00 p.m. with interval of 3 hours in Day 0, 1, 2, 3. It should be recorded when fever occurs in other time.
Severity of fever
Effect of oral pravastatin on the severity of fever (body temperature) after zoledronic acid infusion.
Measured: from 8:00 a.m. to 8:00 p.m. with interval of 4 hours in Day -2 and Day -1, from 9:00 a.m. to 9:00 p.m. with interval of 3 hours in Day 0, 1, 2, 3. It should be recorded when fever occurs in other time.
Occurrence time of pain
Effect of oral pravastatin on the occurrence time of pain after zoledronic acid infusion
Measured: from 8:00 a.m. to 8:00 p.m. with interval of 4 hours in Day -2 and Day -1, from 9:00 a.m. to 9:00 p.m. with interval of 3 hours in Day 0, 1, 2, 3. It should be recorded when pain occurs in other time.
Severity of pain
Effect of oral pravastatin on the severity of pain (visual analogue scale, VAS) after zoledronic acid infusion
Measured: from 8:00 a.m. to 8:00 p.m. with interval of 4 hours in Day -2 and Day -1, from 9:00 a.m. to 9:00 p.m. with interval of 3 hours in Day 0, 1, 2, 3. It should be recorded when pain occurs in other time.
Frequency of acetaminophen usage after zoledronic acid infusion
To compare the frequency of acetaminophen within 72 hours after zoledronic acid infusion between pravastatin arm and placebo arm.
Measured: within 72 hours after zoledronic acid infusion
Amount of acetaminophen usage after zoledronic acid infusion
To compare the amount of acetaminophen within 72 hours after zoledronic acid infusion between pravastatin arm and placebo arm.
Measured: within 72 hours after zoledronic acid infusion
White blood cells
To compare the changes in white blood cells (WBC) count within 48 hours after zoledronic acid infusion between pravastatin arm and placebo arm.
Measured: baseline and 48 hours after infusion
C reaction protein
To compare the changes in C reaction protein (CRP) within 48 hours after zoledronic acid infusion between pravastatin arm and placebo arm.
Measured: baseline and 48 hours after infusion
interferon-γ expression
To compare the changes in interferon-γ (IFN-γ) within 48 hours after zoledronic acid infusion between pravastatin arm and placebo arm.
Measured: baseline and 48 hours after infusion
interleukin-6 expression
To compare the changes in interleukin-6 (IL-6) within 48 hours after zoledronic acid infusion between pravastatin arm and placebo arm.
Measured: baseline and 48 hours after infusion
γδT cells activation
To compare the changes in count of γδT cells activation within 48 hours after zoledronic acid infusion pravastatin arm and placebo arm.
Measured: baseline and 48 hours after infusion
Adverse event occurrence
The occurrence of adverse event within 10 days after zoledronic acid infusion
Measured: 0-10 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2021
- Study startNov 2021 (estimated)
- Primary completionNov 2021 (estimated)
- Study completionApr 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Postmenopausal OsteoporosisStudies of the same condition, open and under way.
- More trials run by Peking University Third HospitalThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 110 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking University Third Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Chunli Song, M.D.; Ph. D., Principal investigator, Peking University Third Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04719481
- Sponsor's protocol ID
- M2020180
- Status last verified
- Jun 2021
- First submitted
- 6 Jan 2021
- Last updated
- 23 Jun 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Sieber P, Lardelli P, Kraenzlin CA, Kraenzlin ME, Meier C. Intravenous bisphosphonates for postmenopausal osteoporosis: safety profiles of zoledronic acid and ibandronate in clinical practice. Clin Drug Investig. 2013 Feb;33(2):117-22. doi: 10.1007/s40261-012-0041-1.
PubMed 23184667Hewitt RE, Lissina A, Green AE, Slay ES, Price DA, Sewell AK. The bisphosphonate acute phase response: rapid and copious production of proinflammatory cytokines by peripheral blood gd T cells in response to aminobisphosphonates is inhibited by statins. Clin Exp Immunol. 2005 Jan;139(1):101-11. doi: 10.1111/j.1365-2249.2005.02665.x.
PubMed 15606619Sireci G, Espinosa E, Di Sano C, Dieli F, Fournie JJ, Salerno A. Differential activation of human gammadelta cells by nonpeptide phosphoantigens. Eur J Immunol. 2001 May;31(5):1628-35. doi: 10.1002/1521-4141(200105)31:53.0.CO;2-T.
PubMed 11465120Schneiders FL, Huijts CM, Reijm M, Bontkes HJ, Verheul HMW, de Gruijl TD, van der Vliet HJ. The effects of systemic treatment with aminobisphosphonates and statins on circulating Vgamma9Vdelta2-T cells in patients with advanced cancer. Immunobiology. 2018 Feb;223(2):171-177. doi: 10.1016/j.imbio.2017.10.029. Epub 2017 Oct 16.
PubMed 29055564Liu Q, Han G, Li R, Fan D, Du G, Zhang M, Tao L, Li H, Liu D, Song C. Reduction effect of oral pravastatin on the acute phase response to intravenous zoledronic acid: protocol for a real-world prospective, placebo-controlled trial. BMJ Open. 2022 Jul 13;12(7):e060703. doi: 10.1136/bmjopen-2021-060703.
PubMed 35831045
Study at a glance
From the registry record, last updated by the sponsor on 23 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Reduction Effect of Oral Pravastatin on Acute Phase Response of Intravenous Zoledronic Acid: a Real-world Study
- ClinicalTrials.gov ID
- NCT04719481
- Acronym / sponsor ID
- M2020180
- Conditions
- Postmenopausal Osteoporosis
- Keywords
- acute phase response, zoledronic acid, pravastatin
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 110 participants (estimated)
- Lead sponsor
- Peking University Third HospitalUniversity, hospital or other
- Study start
- Nov 2021 (estimated)
- Primary completion
- Nov 2021 (estimated)
- Study completion
- Apr 2022 (estimated)
- First posted
- 22 Jan 2021 (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.
Acute phase response (APR) is one of the most common adverse events in osteoporosis with zoledronic acid treatment. It's reported that this reaction is related to the blockade of the mevalonate pathway, leading to isopentenyl pyrophosphate (IPP) accumulation. And the latter can active γδT cells in the circulation, resulting in inflammatory cytokine release. Statins can inhibit the conversion of HMG-CoA to mevalonate that may reduce the accumulation of IPP. Therefore, it is possible that statins can be taken in advance to reduce APR caused by zoledronic acid infusion.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| pravastatin 80mg/d | Experimental | Drug: Pravastatin Sodium 80 MGOral administration of pravastatin at 1 h before zoledronic acid infusion, 24 h and 48 h after zoledronic acid infusion |
| placebo | Placebo comparator | Drug: PlaceboOral administration of placebo at 1 h before zoledronic acid infusion, 24 h and 48 h after zoledronic acid infusion |
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Chinese Han ethnic postmenopausal women.
- Bone mineral density values of less than 2.5 standard deviations (SD) below the normal adult mean.
- Willing to participate in this study.
Key exclusion criteria (12 listed)
- Prior treatment with biphosphonates (oral or intravenous).
- Fever and/or any viral or bacterial infections within 30 days prior to randomization.
- Patients with evidence of any cancer or with a history of cancer.
- Contraindication to zoledronic acid:
- Known hypersensitivity to zoledronic acid or other bisphosphonate or zoledronic acid formulation (excipients); Serum calcium level < 2.13 mmol/L (8.5 mg/dL), free serum calcium level <0.95 mmol/L (3.8 mg/dL) or untreated hypocalcemia; Childbearing or child-breastfeeding women; Creatinine clearance < 35 mL/min;
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 |
|---|---|---|
| Pravastatin Sodium 80 MGAlso: Meibailezhendaily oral administration of 80mg | Drug | pravastatin 80mg/d |
| PlaceboAlso: Meibailezhen placebodaily oral administration | Drug | placebo |
Primary outcome
Incidence of acute phase response
Time frame: 0-72 hours
Effect of oral pravastatin on the incidence of acute phase response within 72 hours after zoledronic acid infusion
12 secondary outcomes
Occurrence time of fever
Time frame: from 8:00 a.m. to 8:00 p.m. with interval of 4 hours in Day -2 and Day -1, from 9:00 a.m. to 9:00 p.m. with interval of 3 hours in Day 0, 1, 2, 3. It should be recorded when fever occurs in other time.
Severity of fever
Time frame: from 8:00 a.m. to 8:00 p.m. with interval of 4 hours in Day -2 and Day -1, from 9:00 a.m. to 9:00 p.m. with interval of 3 hours in Day 0, 1, 2, 3. It should be recorded when fever occurs in other time.
Occurrence time of pain
Time frame: from 8:00 a.m. to 8:00 p.m. with interval of 4 hours in Day -2 and Day -1, from 9:00 a.m. to 9:00 p.m. with interval of 3 hours in Day 0, 1, 2, 3. It should be recorded when pain occurs in other time.
Severity of pain
Time frame: from 8:00 a.m. to 8:00 p.m. with interval of 4 hours in Day -2 and Day -1, from 9:00 a.m. to 9:00 p.m. with interval of 3 hours in Day 0, 1, 2, 3. It should be recorded when pain occurs in other time.
Frequency of acetaminophen usage after zoledronic acid infusion
Time frame: within 72 hours after zoledronic acid infusion
Amount of acetaminophen usage after zoledronic acid infusion
Time frame: within 72 hours after zoledronic acid infusion
White blood cells
Time frame: baseline and 48 hours after infusion
C reaction protein
Time frame: baseline and 48 hours after infusion
interferon-γ expression
Time frame: baseline and 48 hours after infusion
interleukin-6 expression
Time frame: baseline and 48 hours after infusion
γδT cells activation
Time frame: baseline and 48 hours after infusion
Adverse event occurrence
Time frame: 0-10 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2021.
- Background: PubMed 23184667Sieber P, Lardelli P, Kraenzlin CA, Kraenzlin ME, Meier C. Intravenous bisphosphonates for postmenopausal osteoporosis: safety profiles of zoledronic acid and ibandronate in clinical practice. Clin Drug Investig. 2013 Feb;33(2):117-22. doi: 10.1007/s40261-012-0041-1.
- Background: PubMed 15606619Hewitt RE, Lissina A, Green AE, Slay ES, Price DA, Sewell AK. The bisphosphonate acute phase response: rapid and copious production of proinflammatory cytokines by peripheral blood gd T cells in response to aminobisphosphonates is inhibited by statins. Clin Exp Immunol. 2005 Jan;139(1):101-11. doi: 10.1111/j.1365-2249.2005.02665.x.
- Background: PubMed 11465120Sireci G, Espinosa E, Di Sano C, Dieli F, Fournie JJ, Salerno A. Differential activation of human gammadelta cells by nonpeptide phosphoantigens. Eur J Immunol. 2001 May;31(5):1628-35. doi: 10.1002/1521-4141(200105)31:53.0.CO;2-T.
- Background: PubMed 29055564Schneiders FL, Huijts CM, Reijm M, Bontkes HJ, Verheul HMW, de Gruijl TD, van der Vliet HJ. The effects of systemic treatment with aminobisphosphonates and statins on circulating Vgamma9Vdelta2-T cells in patients with advanced cancer. Immunobiology. 2018 Feb;223(2):171-177. doi: 10.1016/j.imbio.2017.10.029. Epub 2017 Oct 16.
- Derived from this study: PubMed 35831045Liu Q, Han G, Li R, Fan D, Du G, Zhang M, Tao L, Li H, Liu D, Song C. Reduction effect of oral pravastatin on the acute phase response to intravenous zoledronic acid: protocol for a real-world prospective, placebo-controlled trial. BMJ Open. 2022 Jul 13;12(7):e060703. doi: 10.1136/bmjopen-2021-060703.
- 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.
Chunli Song, M.D.; Ph. D. principal investigator
Peking University Third Hospital
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Pravastatin Sodium 80 MG in people with Postmenopausal Osteoporosis, run by Peking University Third Hospital.
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 3 inclusion and 12 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: status not confirmed, as of the sponsor's last update on 23 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Qi Liu, Ph. D. (+8615501060136, liuqicpu@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of acute phase response (time frame: 0-72 hours). 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 NCT04719481, which also lists 5 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 23 Jun 2021.