Back to resultsPravastatin Reduces Acute Phase Response of Zoledronic Acid
Primary Purpose
Postmenopausal Osteoporosis
Status
Unknown status
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Pravastatin Sodium 80 MG
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Postmenopausal Osteoporosis focused on measuring acute phase response, zoledronic acid, pravastatin
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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:
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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
pravastatin 80mg/d
placebo
Arm Description
Oral administration of pravastatin at 1 h before zoledronic acid infusion, 24 h and 48 h after zoledronic acid infusion
Oral administration of placebo at 1 h before zoledronic acid infusion, 24 h and 48 h after zoledronic acid infusion
Outcomes
Primary Outcome Measures
Incidence of acute phase response
Effect of oral pravastatin on the incidence of acute phase response within 72 hours after zoledronic acid infusion
Secondary Outcome Measures
Occurrence time of fever
Effect of oral pravastatin on the occurrence time of fever after zoledronic acid infusion
Severity of fever
Effect of oral pravastatin on the severity of fever (body temperature) after zoledronic acid infusion.
Occurrence time of pain
Effect of oral pravastatin on the occurrence time of pain after zoledronic acid infusion
Severity of pain
Effect of oral pravastatin on the severity of pain (visual analogue scale, VAS) after zoledronic acid infusion
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.
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.
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.
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.
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.
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.
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.
Adverse event occurrence
The occurrence of adverse event within 10 days after zoledronic acid infusion
Full Information
NCT ID
NCT04719481
First Posted
January 6, 2021
Last Updated
June 17, 2021
Sponsor
Peking University Third Hospital
1. Study Identification
Unique Protocol Identification Number
NCT04719481
Brief Title
Pravastatin Reduces Acute Phase Response of Zoledronic Acid
Official Title
The Reduction Effect of Oral Pravastatin on Acute Phase Response of Intravenous Zoledronic Acid: a Real-world Study
Study Type
Interventional
2. Study Status
Record Verification Date
June 2021
Overall Recruitment Status
Unknown status
Study Start Date
November 2021 (Anticipated)
Primary Completion Date
November 2021 (Anticipated)
Study Completion Date
April 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Peking University Third Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief 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. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Postmenopausal Osteoporosis
Keywords
acute phase response, zoledronic acid, pravastatin
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
110 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
pravastatin 80mg/d
Arm Type
Experimental
Arm Description
Oral administration of pravastatin at 1 h before zoledronic acid infusion, 24 h and 48 h after zoledronic acid infusion
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
Oral administration of placebo at 1 h before zoledronic acid infusion, 24 h and 48 h after zoledronic acid infusion
Intervention Type
Drug
Intervention Name(s)
Pravastatin Sodium 80 MG
Other Intervention Name(s)
Meibailezhen
Intervention Description
daily oral administration of 80mg
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Meibailezhen placebo
Intervention Description
daily oral administration
Primary Outcome Measure Information:
Title
Incidence of acute phase response
Description
Effect of oral pravastatin on the incidence of acute phase response within 72 hours after zoledronic acid infusion
Time Frame
0-72 hours
Secondary Outcome Measure Information:
Title
Occurrence time of fever
Description
Effect of oral pravastatin on the occurrence time of fever after zoledronic acid infusion
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.
Title
Severity of fever
Description
Effect of oral pravastatin on the severity of fever (body temperature) after zoledronic acid infusion.
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.
Title
Occurrence time of pain
Description
Effect of oral pravastatin on the occurrence time of pain after zoledronic acid infusion
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.
Title
Severity of pain
Description
Effect of oral pravastatin on the severity of pain (visual analogue scale, VAS) after zoledronic acid infusion
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.
Title
Frequency of acetaminophen usage after zoledronic acid infusion
Description
To compare the frequency of acetaminophen within 72 hours after zoledronic acid infusion between pravastatin arm and placebo arm.
Time Frame
within 72 hours after zoledronic acid infusion
Title
Amount of acetaminophen usage after zoledronic acid infusion
Description
To compare the amount of acetaminophen within 72 hours after zoledronic acid infusion between pravastatin arm and placebo arm.
Time Frame
within 72 hours after zoledronic acid infusion
Title
White blood cells
Description
To compare the changes in white blood cells (WBC) count within 48 hours after zoledronic acid infusion between pravastatin arm and placebo arm.
Time Frame
baseline and 48 hours after infusion
Title
C reaction protein
Description
To compare the changes in C reaction protein (CRP) within 48 hours after zoledronic acid infusion between pravastatin arm and placebo arm.
Time Frame
baseline and 48 hours after infusion
Title
interferon-γ expression
Description
To compare the changes in interferon-γ (IFN-γ) within 48 hours after zoledronic acid infusion between pravastatin arm and placebo arm.
Time Frame
baseline and 48 hours after infusion
Title
interleukin-6 expression
Description
To compare the changes in interleukin-6 (IL-6) within 48 hours after zoledronic acid infusion between pravastatin arm and placebo arm.
Time Frame
baseline and 48 hours after infusion
Title
γδT cells activation
Description
To compare the changes in count of γδT cells activation within 48 hours after zoledronic acid infusion pravastatin arm and placebo arm.
Time Frame
baseline and 48 hours after infusion
Title
Adverse event occurrence
Description
The occurrence of adverse event within 10 days after zoledronic acid infusion
Time Frame
0-10 days
10. Eligibility
Sex
Female
Gender Based
Yes
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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:
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Qi Liu, Ph. D.
Phone
+8615501060136
Email
liuqicpu@hotmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chunli Song, M.D.; Ph. D.
Organizational Affiliation
Peking University Third Hospital
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
23184667
Citation
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.
Results Reference
background
PubMed Identifier
15606619
Citation
Hewitt 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.
Results Reference
background
PubMed Identifier
11465120
Citation
Sireci 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.
Results Reference
background
PubMed Identifier
29055564
Citation
Schneiders 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.
Results Reference
background
PubMed Identifier
35831045
Citation
Liu 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.
Results Reference
derived
Learn more about this trial
Pravastatin Reduces Acute Phase Response of Zoledronic Acid
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