Pravastatin Reduces Acute Phase Response of Zoledronic Acid

Peking University

Status and phase: Unknown; Phase 4

Conditions: Postmenopausal Osteoporosis

Treatments: Drug: Placebo; Drug: Pravastatin Sodium 80 MG

Study type: Interventional

Funder types: Other

Identifiers

NCT04719481

M2020180

Details and patient eligibility

About

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.

Enrollment: 110 estimated patients

Sex: Female

Volunteers: Accepts Healthy Volunteers

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.

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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110 participants in 2 patient groups, including a placebo group

pravastatin 80mg/d

Experimental group

Description:

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

Treatment:

Drug: Pravastatin Sodium 80 MG

placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo