Pravastatin Reduces Acute Phase Response of Zoledronic Acid

NCT04719481 | Unknown Phase 4

• 1 other identifier: M2020180
• Study Type: interventional
• Target: 110
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Postmenopausal Osteoporosis

Keywords

acute phase response; zoledronic acid; pravastatin

Outcome Measures

Primary Outcomes (1)

• Incidence of acute phase response

  Effect of oral pravastatin on the incidence of acute phase response within 72 hours after zoledronic acid infusion

  0-72 hours

Secondary Outcomes (12)

• 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.

• 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.

• 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.

• 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.

• Frequency of acetaminophen usage after zoledronic acid infusion

  within 72 hours after zoledronic acid infusion

Study Arms (2)

pravastatin 80mg/d

EXPERIMENTAL

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

placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Pravastatin Sodium 80 MG DRUG

daily oral administration of 80mg

Also known as: Meibailezhen

pravastatin 80mg/d

Placebo DRUG

daily oral administration

Also known as: Meibailezhen placebo

placebo

Eligibility Criteria

• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Peking University Third Hospital: lead

Related Publications (5)

• 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.

  PMID: 23184667 BACKGROUND

• 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.

  PMID: 15606619 BACKGROUND

• 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.

  PMID: 11465120 BACKGROUND

• 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.

  PMID: 29055564 BACKGROUND

• 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.

  PMID: 35831045 DERIVED

MeSH Terms

Conditions

Osteoporosis, Postmenopausal; Acute-Phase Reaction

Interventions

Pravastatin

Condition Hierarchy (Ancestors)

Osteoporosis; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Chunli Song, M.D.; Ph. D.

  Peking University Third Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Qi Liu, Ph. D.

CONTACT

+8615501060136; liuqicpu@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2021
• First Posted: January 22, 2021
• Study Start: November 1, 2021
• Primary Completion: November 1, 2021
• Study Completion: April 1, 2022
• Last Updated: June 23, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share