The effectiveness of atorvastatin for deep vein thrombosis prevention in cancer patients undergoing chemotherapy
| ISRCTN | ISRCTN71891829 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN71891829 |
| Secondary identifying numbers | BS-VTE-001 |
- Submission date
- 15/12/2020
- Registration date
- 17/12/2020
- Last edited
- 25/03/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Circulatory System
Plain English summary of protocol
Background and study aims
Venous thromboembolism (VTE) is a condition in which a blood clot forms in the deep veins of the leg, groin or arm and travels in the blood circulation. The incidence of VTE is increased in cancer patients and even more in patients who undergo chemotherapy. Most occur right after the chemotherapy is started.
VTE is a leading cause of increased death and illness, delay of care, and economic burden in cancer patients. One of the most common VTEs is deep vein thrombosis (DVT) and there is a three times higher risk of death in patients with asymptomatic DVT.
Previous studies have proven the effectiveness and safety of thrombo-prophylaxis (preventing the formation of blood clots) in medically ill and cancer patients, so a recommendation for this has been made for clinical practice. However, there are still a lot of clinicians not using thrombo-prophylaxis in daily use, the most common reasons are the cost, bleeding risk, and lack of knowledge, confidence, and awareness to use an anticoagulant drug as thrombo-prophylaxis.
The immune system and inflammation have long been recognized as playing roles in cancer-related VTE. Statins have an anti-inflammatory effect so might have a benefit with a lower bleeding risk, lower cost, and easier use compared to conventional anticoagulants. There is still limited data about statins and their role in preventing VTE cancer patients who undergo chemotherapy still needs to be confirmed.
Rivaroxaban is an anticoagulant with a relatively convenient use, a single dose orally daily. A previous study has proven that rivaroxaban could reduce thrombosis events with a low bleeding risk. Rivaroxaban also does not need daily coagulation monitoring.
The study aims to compare the effectiveness of atorvastatin and rivaroxaban for DVT prevention, inflammation and coagulation in cancer patients who have a high risk of thrombosis while undergoing chemotherapy.
Who can participate?
Patients aged 18-60 with cancer and no previous chemotherapy
What does the study involve?
Participants are randomly allocated to take either atorvastatin or rivaroxaban daily for 3 months for DVT prevention. Participants are assessed with Doppler ultrasonography at the start of the study and after 3 months.
What are the possible benefits and risks of participating?
The researchers think that atorvastatin will be as effective as rivaroxaban in DVT prevention but at a lower cost. The common side effects of atorvastatin are increased liver function tests, myopathy, joint pain, and muscle weakness. However, these side effects are usually well-tolerated and severe adverse events are rarely found. The most common side effect of rivaroxaban is bleeding in the gums, skin and with urinating or defecating. Participants will be monitored for the adverse events and will be treated.
Where is the study run from?
Dr. Kariadi Hospital (Indonesia)
When is the study starting and how long is it expected to run for?
November 2020 to March 2022
Who is funding the study?
Investigator initiated and funded
Who is the main contact?
Dr Budi Setiawan
boedhi_smg73@yahoo.com
Contact information
Scientific
RSUP Dr. Kariadi Semarang
Sutomo St No. 16
Semarang
50244
Indonesia
 ORCID ID |
0000-0002-8654-6746 |
|---|---|
| Phone | +62 (0)858 6511 8118 |
| boedhi_smg73@yahoo.com |
Study information
| Study design | Single-center interventional double-blinded randomized controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Prevention |
| Participant information sheet | ISRCTN71891829_PIS_16Dec20.pdf |
| Scientific title | Comparing the effectiveness between the use of atorvastatin and rivaroxaban for deep vein thrombosis prophylaxis, inflammatory responses, and coagulation activities in cancer patients who have a high risk of thrombosis while undergoing chemotherapy: focus on IL-6, CRP, TF, F1+2, D-dimer, NF-kB, and TNF-alpha serum level and Doppler ultrasonography |
| Study objectives | 1. Atorvastatin 20 mg administration for 3 months can be used as an alternative for thrombo-prophylaxis in cancer patients who have a high risk of thrombosis while undergoing chemotherapy 2. Atorvastatin 20 mg is as effective as rivaroxaban and has better cost-effectiveness for thrombo-prophylaxis in cancer patients who have a high risk of thrombosis while undergoing chemotherapy 3. Atorvastatin 20 mg administration for 3 months is not inferior compared to rivaroxaban as a thrombo-prophylaxis in cancer patients who have a high risk of thrombosis while undergoing chemotherapy 4. Atorvastatin 20 mg administration for 3 months will reduce the IL-6, CRP, TF, F1+2, D-dimer, NF-kB, and TNF-alpha serum level and reduce DVT incidence measured by Doppler ultrasonography |
| Ethics approval(s) | Approved 24/11/2020, Health Research Ethics Committee RSUP Dr. Kariadi Semarang (Sutomo St no. 16, Indonesia; +62 (0)24 8413476; kepk.rskariadi@gmail.com), ref: 665/EC/KEPK-RSDK/2020 |
| Health condition(s) or problem(s) studied | Prevention of deep vein thrombosis in cancer patients who have high risk of thrombosis while undergoing chemotherapy |
| Intervention | Participants who meet the inclusion criteria will be randomized with simple randomization into the study group (atorvastatin 20 mg daily orally) or the control group (rivaroxaban 10 mg daily orally) for 3 months. At baseline Doppler ultrasonography is performed on the lower extremities; IL-6, CRP, TF, F1+2, D-dimer, NF-kB and TNF-alpha serum levels are measured and re-measured after 3 months. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Atorvastatin, rivaroxaban |
| Primary outcome measure | Deep vein thrombosis event measured using Doppler ultrasonography at baseline and 3 months |
| Secondary outcome measures | 1. IL-6 is measured using ELISA at baseline and 3 months 2. NF-kB is measured using ELISA at baseline and 3 months 3. CRP is measured using a spectrophotometer at baseline and 3 months 4. TF is measured using ELISA at baseline and 3 months 5. F1+2 is measured using ELISA at baseline and 3 months 6. D-dimer is measured using ELISA at baseline and 3 months 7. TNF-alpha is measured using ELISA at baseline and 3 months 8. Cost effectiveness is measured using the total cost for each subject |
| Overall study start date | 24/11/2020 |
| Completion date | 28/02/2022 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 60 Years |
| Sex | Both |
| Target number of participants | 80 |
| Total final enrolment | 86 |
| Key inclusion criteria | 1. Cancer patient with a definite diagnosis of cancer based on anatomy pathological examination 2. Cancer patients who have not received any chemotherapy 3. Khorana risk score ≥2 4. Age 18-60 years old 5. Has signed the participant agreement |
| Key exclusion criteria | 1. Deep vein thrombosis diagnosed with Doppler ultrasonography examination at baseline 2. Within 14 days post-surgery 3. Pregnancy 4. Taking an anti-thrombotic drug 5. Congenital altered coagulation system 6. Creatinine clearance <30 ml/minute 7. Patients with AST level >3x upper normal limit 8. Patients with total bilirubin total >5 mg/dl 9. Patients with CK >3 x upper normal limit 10. Performance status ECOC ≥3 11. Patients with cardio-cerebrovascular disease 12. Patients with infection 13. Patients with active, major, serious, life-threatening bleeding that can not be overcome with medical or surgical intervention, esp in a critical area (intra-cranial, pericardial, retroperitoneal, intra-occular, intra-artikular, intraspinal) 14. Malignant hypertension 15. Congenital coagulopathy or severe platelet dysfunction 16. Severe and persistent thrombocytopenia (<20,000/µl) |
| Date of first enrolment | 04/01/2021 |
| Date of final enrolment | 30/11/2021 |
Locations
Countries of recruitment
- Indonesia
Study participating centre
Semarang
50244
Indonesia
Sponsor information
Hospital/treatment centre
Sutomo St. No. 16
Semarang
50244
Indonesia
| Phone | +62 (0)24 8413476 |
|---|---|
| kepk.rskariadi@gmail.com | |
| Website | http://www.rskariadi.co.id/ |
"ROR" |
https://ror.org/040f86t49 |
Funders
Funder type
Other
No information available
Results and Publications
| Intention to publish date | 01/11/2022 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal. The study protocol will not be available or published. |
| IPD sharing plan | Current individual participant data (IPD) sharing statement as of 21/02/2022: The data sets generated during and/or analysed during the current study are/will be available upon request via email to Budi Setiawan (boedhi_smg73@yahoo.com) when the data will become available. The raw data will be available for 2 years. Previous individual participant data (IPD) sharing statement: The datasets generated during and/or analysed during the current study are/will be available upon request (please email your request to boedhi_smg73@yahoo.com, Budi Setiawan). |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | 16/12/2020 | 22/12/2020 | No | Yes | |
| Protocol file | 23/08/2022 | No | No | ||
| Preprint results | 21/10/2022 | 27/10/2022 | No | No | |
| Results article | Primary efficacy end point | 08/05/2023 | 09/05/2023 | Yes | No |
| Results article | Secondary outcome results | 19/03/2025 | 25/03/2025 | Yes | No |
Additional files
- ISRCTN71891829_PIS_16Dec20.pdf
- Uploaded 22/12/2020
- ISRCTN71891829_PROTOCOL.pdf
Editorial Notes
25/03/2025: Publication reference added.
09/05/2023: Publication reference added.
27/10/2022: Preprint added.
23/08/2022: Protocol file uploaded.
18/08/2022: The intention to publish date was changed from 30/06/2022 to 01/11/2022.
21/02/2022: The individual participant data (IPD) sharing statement has been updated
20/12/2021: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/12/2021 to 30/11/2021.
2. The overall end date was changed from 31/03/2022 to 28/02/2022.
3. The total final enrolment number has been added.
19/11/2021: The following changes have been made:
1. The recruitment end date has been changed from 24/11/2021 to 31/12/2021.
2. The overall trial end date has been changed from 01/01/2022 to 31/03/2022 and the plain English summary has been updated to reflect this change.
3. The intention to publish date has been changed from 03/03/2022 to 30/06/2022.
4. The individual participant data (IPD) sharing statement has been added.
05/01/2021: The following changes were made to the trial record:
1. The recruitment start date was changed from 01/01/2021 to 04/01/2021.
2. The recruitment end date was changed from 01/10/2021 to 24/11/2021.
22/12/2020: The participant information sheet has been uploaded as an additional file.
16/12/2020: Trial's existence confirmed by Health Research Ethics Committee RSUP Dr. Kariadi Semarang.
