Pilot Study of Rosuvastatin and Enoxaparin Thromboprophylaxis Following Ovarian Cancer Surgery (O-STAT Study)

• ClinicalTrials.gov Identifier: NCT03532139
• Recruitment Status: Active, not recruiting
• First Posted: May 22, 2018
• Last Update Posted: July 20, 2022
• Sponsor: Beth Israel Deaconess Medical Center
• Collaborators: National Institutes of Health (NIH); National Heart, Lung, and Blood Institute (NHLBI)
• Information provided by (Responsible Party): Jeffrey Zwicker, MD, Beth Israel Deaconess Medical Center

Study Description

Brief Summary:

This research study is studying a combination of two drug interventions called rosuvastatin and enoxaparin as a possible preventative measure against developing venous blood clots (such deep vein thrombosis or pulmonary embolism). .

The drugs involved in this study are:

• Rosuvastatin, also known as Crestor
• Enoxaparin

Condition or disease	Intervention/treatment	Phase
Ovarian Cancer	Drug: Enoxaparin; Drug: Enoxaparin + Rosuvastatin; Other: Thromboprophylaxis	Phase 2

Detailed Description:

This is a randomized pilot trial to estimate the effect of rosuvastatin on levels of tissue factor bearing microparticles (TFMP) in patients undergoing surgery for presumed ovarian cancer (including primary peritoneal and fallopian tube carcinoma). Women will either be randomized to enoxaparin subcutaneously once daily (Arm A) or enoxaparin in combination with rosuvastatin (Arm B). Arm C will receive thromboprophylaxis according to standard of care and not be randomized. Levels of circulating TFMP will be assessed in all patients on Day 1 and following surgery (days 15, 30 and day 60). A bilateral lower extremity ultrasound will be performed on days 30 and 60 for all participants to estimate the rate of VTE in the 3 arms.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Patients will be randomized to Arm Enoxaparin and Arm Enoxaparin + Rosuvastatin, and those requesting no randomization willl be directly assigned to Arm Standard-of-care Thromboprophylaxis
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Pilot Study of Rosuvastatin and Enoxaparin Thromboprophylaxis Following Ovarian Cancer Surgery (O-STAT Study)
• Actual Study Start Date: July 25, 2018
• Estimated Primary Completion Date: December 31, 2022
• Estimated Study Completion Date: May 31, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Enoxaparin; -Enoxaparin is administered subcutaneous daily	Drug: Enoxaparin; Enoxaparin is used for prevention of blood clots following abdominal or orthopedic surgery and in medical patients with restricted mobility during acute illness
Experimental: Enoxaparin + Rosuvastatin; Enoxaparin is administered subcutaneous daily.; Rosuvastatin is administered daily orally starting on day 15	Drug: Enoxaparin; Enoxaparin is used for prevention of blood clots following abdominal or orthopedic surgery and in medical patients with restricted mobility during acute illness; Drug: Enoxaparin + Rosuvastatin; Rosuvastatin is an anti-cholesterol medication that is FDA (the U.S. Food and Drug Administration) approved to lower cholesterol and reduce the risk of arterial blood clots. There is evidence that rosuvastatin can lower the risk of venous blood clots in healthy individuals Enoxaparin is used for prevention of blood clots following abdominal or orthopedic surgery and in medical patients with restricted mobility during acute illness
Experimental: Thromboprophylaxis; -Thromboprophylaxis is administered per clinician discretion	Other: Thromboprophylaxis; standard of care therapy

Outcome Measures

Primary Outcome Measures :

1. Comparison of differences in circulating tissue factor bearing microparticles between study arms [ Time Frame: 60 days ]
   Concentration of tissue factor bearing microparticles

Secondary Outcome Measures :

1. Point estimate of the rates of VTE following ovarian surgery in each study arm [ Time Frame: 60 days ]
   VTE rate
2. Comparison of D-dimer values across study arms [ Time Frame: 60 days ]
   D-dimer concentration
3. Compare the rates of VTE between study arms [ Time Frame: 60 days ]
   VTE rate in arm A and B
4. Compare CRP between study arms [ Time Frame: 60 days ]
   CRP concentration
5. Compare concentrations of TFMP, D-dimer, CRP at study timepoints. [ Time Frame: 60 days ]
   Baseline vs day 60 comparison for TFMP, D-dimer, CRP on each arm
6. Assess incidence of major hemorrhage and clinically relevant bleeding as defined by the International Society of Thrombosis and Haemostasis [ Time Frame: 60 days ]
   Major and clinically relevant non-major bleeding rates
7. Estimate the overall rate of any VTE [ Time Frame: 60 days ]
   Overall VTE rates

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Histologic diagnosis of ovarian, fallopian or primary peritoneal cancer (excluding borderline histologies). Preliminary pathology results based on frozen section findings are acceptable.
• The interval between pelvic or abdominal surgery and first dose of study treatment must be no more than 10 days.
• Age ≥ 18 years.
• ECOG performance status ≤2 (see Appendix A)
• Life expectancy of greater than 6 months

• Participants must have normal organ and marrow function as defined below:

  • Platelets ≥ 100,000/mcL
  • Total Bilirubin <1.5 mg/dL (or direct bilirubin <1.0 mg/dL)
  • AST(SGOT) ≤ 1.5 × institutional upper limit of normal
  • ALT(SGPT) ≤ 1.5 × institutional upper limit of normal
  • Creatinine < 1.5 mg/dL OR
  • Estimated creatinine clearance ≥60 mL/min/1.73 m2
• The effects of rosuvastatin on the developing human fetus are unknown. For this reason and because statins used in this trial are thought to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Participants who are receiving any other investigational agents.
• Participants with known brain metastases should be excluded from this clinical trial because of their poor prognosis and increased risk of intracranial hemorrhage
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to enoxaparin or atorvastatin
• Active bleeding or high risk of bleeding (e.g. known acute gastrointestinal ulcer)
• History of heparin-induced thrombocytopenia.
• Any history of significant hemorrhage (requiring hospitalization or transfusion) outside of a surgical setting within the last year.

• Presence of coagulopathy defined as:

  • PT > 1.3 x upper limit of normal
  • PTT > 1.3 x upper limit of normal
• Uncontrolled hypothyroidism (defined as TSH below lower limit of normal). Qualifying TSH may be within 60 days prior to enrollment. If screening TSH is low, patients are eligible if free T4 is within normal limits.
• Familial bleeding diathesis
• Known diagnosis of disseminated intravascular coagulation
• Currently taking statin (i.e. rosuvastatin, atorvastatin, simvastatin) or fibrates
• Currently receiving anticoagulant therapy
• Current use of aspirin (>81 mg daily), Clopidogrel (Plavix), cilostazol (Pletal), aspirin-dipyridamole (Aggrenox).
• Known Asian descent (including Filipino, Chinese, Japanese, Korean, Vietnamese or Asian-Indian origin) due to altered metabolism of statins.
• Concomitant use of the following drugs: cyclosporine, fibrates, niacin, gemfibrozil, ketoconazole, spironolactone, cimetidine, warfarin, erythromycin, or protease inhibitors
• Known recent history of heavy alcohol use
• History of rhabdomyolysis while on statin therapy.
• Known active Hepatitis C or active Hepatitis B infection.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study due to the potential for teratogenic effects on the human fetus. Because there is an unknown but potential risk of adverse events in nursing infants secondary to the treatment of the mother with rosuvastatin, breastfeeding should be discontinued. These potential risks may also apply to other agents used in this study.

Contacts and Locations

Locations

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02214

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States, 02215

Sponsors and Collaborators

Beth Israel Deaconess Medical Center

National Institutes of Health (NIH)

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Jeffrey Zwicker, MD; Beth Israel Deaconess Medical Center

More Information

• Responsible Party: Jeffrey Zwicker, MD, Principal Investigator, Beth Israel Deaconess Medical Center
• ClinicalTrials.gov Identifier: NCT03532139
• Other Study ID Numbers: 18-067; 1R34HL135226-01 ( U.S. NIH Grant/Contract )
• First Posted: May 22, 2018
• Last Update Posted: July 20, 2022
• Last Verified: July 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Jeffrey Zwicker, MD, Beth Israel Deaconess Medical Center:

Ovarian Cancer

Additional relevant MeSH terms:

Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Endocrine System Diseases; Gonadal Disorders; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Enoxaparin; Enoxaparin sodium; Rosuvastatin Calcium; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Enzyme Inhibitors; Anticoagulants; Fibrinolytic Agents; Fibrin Modulating Agents