Pravastatin Reduces Acute Phase Response of Zoledronic Acid

Sponsor

Peking University Third Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04719481

Collaborator

(none)

110

Enrollment

Arms

Anticipated Duration (Months)

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Postmenopausal Osteoporosis	Drug: Pravastatin Sodium 80 MG Drug: Placebo	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

110 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

The Reduction Effect of Oral Pravastatin on Acute Phase Response of Intravenous Zoledronic Acid: a Real-world Study

Anticipated Study Start Date :

Nov 1, 2021

Anticipated Primary Completion Date :

Nov 1, 2021

Anticipated Study Completion Date :

Apr 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: pravastatin 80mg/d Oral administration of pravastatin at 1 h before zoledronic acid infusion, 24 h and 48 h after zoledronic acid infusion	Drug: Pravastatin Sodium 80 MG daily oral administration of 80mg Other Names: Meibailezhen
Placebo Comparator: placebo Oral administration of placebo at 1 h before zoledronic acid infusion, 24 h and 48 h after zoledronic acid infusion	Drug: Placebo daily oral administration Other Names: Meibailezhen placebo

Arm

Intervention/Treatment

Experimental: pravastatin 80mg/d

Oral administration of pravastatin at 1 h before zoledronic acid infusion, 24 h and 48 h after zoledronic acid infusion

Drug: Pravastatin Sodium 80 MG

daily oral administration of 80mg

Other Names:

Meibailezhen

Placebo Comparator: placebo

Oral administration of placebo at 1 h before zoledronic acid infusion, 24 h and 48 h after zoledronic acid infusion

Drug: Placebo

daily oral administration

Other Names:

Meibailezhen placebo

Outcome Measures

Primary Outcome Measures

Incidence of acute phase response [0-72 hours]
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 [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.]
Effect of oral pravastatin on the occurrence time of fever after zoledronic acid infusion
Severity of fever [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.]
Effect of oral pravastatin on the severity of fever (body temperature) after zoledronic acid infusion.
Occurrence time of pain [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.]
Effect of oral pravastatin on the occurrence time of pain after zoledronic acid infusion
Severity of pain [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.]
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 [within 72 hours 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 [within 72 hours 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 [baseline and 48 hours after infusion]
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 [baseline and 48 hours after infusion]
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 [baseline and 48 hours after infusion]
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 [baseline and 48 hours after infusion]
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 [baseline and 48 hours after infusion]
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 [0-10 days]
The occurrence of adverse event within 10 days after zoledronic acid infusion

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

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.