Pravastatin Reduces Acute Phase Response of Zoledronic Acid

June 17, 2021 updated by: Peking University Third Hospital

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

110

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
0-72 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Effect of oral pravastatin on the occurrence time of fever after zoledronic acid infusion
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.
Effect of oral pravastatin on the severity of fever (body temperature) after zoledronic acid infusion.
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.
Effect of oral pravastatin on the occurrence time of pain after zoledronic acid infusion
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.
Effect of oral pravastatin on the severity of pain (visual analogue scale, VAS) after zoledronic acid infusion
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
To compare the frequency of acetaminophen within 72 hours after zoledronic acid infusion between pravastatin arm and placebo arm.
within 72 hours after zoledronic acid infusion
Amount of acetaminophen usage after zoledronic acid infusion
Time Frame: 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.
within 72 hours after zoledronic acid infusion
White blood cells
Time Frame: 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.
baseline and 48 hours after infusion
C reaction protein
Time Frame: 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.
baseline and 48 hours after infusion
interferon-γ expression
Time Frame: 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.
baseline and 48 hours after infusion
interleukin-6 expression
Time Frame: 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.
baseline and 48 hours after infusion
γδT cells activation
Time Frame: 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.
baseline and 48 hours after infusion
Adverse event occurrence
Time Frame: 0-10 days
The occurrence of adverse event within 10 days after zoledronic acid infusion
0-10 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peking University Third Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

November 1, 2021

Primary Completion (Anticipated)

November 1, 2021

Study Completion (Anticipated)

April 1, 2022

Study Registration Dates

First Submitted

January 6, 2021

First Submitted That Met QC Criteria

January 19, 2021

First Posted (Actual)

January 22, 2021

Study Record Updates

Last Update Posted (Actual)

June 23, 2021

Last Update Submitted That Met QC Criteria

June 17, 2021

Last Verified

June 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • M2020180

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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