Pravastatin Reduces Acute Phase Response of Zoledronic Acid

Phase 4

• Conditions: Postmenopausal Osteoporosis
• Interventions: Drug: Placebo; Drug: Pravastatin Sodium 80 MG

• Registration Number: NCT04719481
• Lead Sponsor: Peking University Third Hospital

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-01-06
• Study First Submitted QC: 2021-01-19
• Study First Posted: 2021-01-22
• Status Verified: 2021-06
• Last Update Submitted: 2021-06-17
• Last Update Posted: 2021-06-23
• Study Start: 2021-11
• Primary Completion: 2021-11
• Study Completion: 2022-04

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 110

Inclusion Criteria

1. Chinese Han ethnic postmenopausal women.
2. Bone mineral density values of less than 2.5 standard deviations (SD) below the normal adult mean.
3. Willing to participate in this study.

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Exclusion Criteria

1. Prior treatment with biphosphonates (oral or intravenous).

2. Fever and/or any viral or bacterial infections within 30 days prior to randomization.

3. Patients with evidence of any cancer or with a history of cancer.

4. 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.

5. 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.

6. Any physiological or medical condition which, in the opinion of the investigator, would preclude the participant from this trail.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
placebo	Placebo	Oral administration of placebo at 1 h before zoledronic acid infusion, 24 h and 48 h after zoledronic acid infusion
pravastatin 80mg/d	Pravastatin Sodium 80 MG	Oral administration of pravastatin at 1 h before zoledronic acid infusion, 24 h and 48 h after zoledronic acid infusion

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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