Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT03240120
Other study ID # HKU-OTI-01
Secondary ID
Status Recruiting
Phase Phase 3
First received
Last updated
Start date September 1, 2017
Est. completion date December 31, 2021

Study information

Verified date April 2019
Source The University of Hong Kong
Contact Gloria Hwang, MBBS
Phone 852 22553111
Email yyhwang922@gmail.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This trial aims at determining if dabigatran is effective in the treatment of malignancy associated VTE. Tolerance and safety of dabigatran will also be assessed.

This is a single armed trial of dabigatran in patients with malignancy associated VTE.

The target recruitment is 99 consecutive patients with active malignancy and newly diagnosed VTE (deep vein thrombosis and/or pulmonary embolism) in Queen Mary Hospital.

Tinzaparin 175 iu/kg daily will be started after the diagnosis of VTE is confirmed (duplex Doppler ultrasonography for deep vein thrombosis, and computed tomography for pulmonary embolism), and a written consent is obtained. Patients will be switched to dabigatran 150mg twice daily from day 6 onwards. The first dose of dabigatran will be given within 2 hours before the time that the next dose of tinzaparin would have been due. Anticoagulation will be continued as long as malignancy is active. If patients achieve a complete remission of their underlying malignancies, dabigatran will be continued for 6 months further.


Description:

Patients with malignancies are at increased risks of venous thromboembolism (VTE). The annual incidence of VTE in cancer patients is 0.5%, which is 5-fold more than the general population . Low molecular weight heparin (LMWH) has been the standard treatment for malignancy-associated VTE. This recommendation follows the results of the Randomized Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent VenousThromboembolism in Patients with Cancer (CLOT) trial, which showed superiority of Low molecular weight heparin (LMWH) over warfarin in cancer patients with VTE .

Low molecular weight heparin (LMWH) has a number of inherent advantages over warfarin. It does not interact with chemotherapeutic agents, and dose titration is not necessary. Furthermore, the risks of both bleeding and breakthrough VTE are also lower with LMWH. However, the requirement of daily subcutaneous injection makes LWMH inconvenient to use. Most patients have difficulties continuing daily injection, partly owing to compliance issues, but also because an emaciated state in some patients makes subcutaneous injection painful. As the life expectancy of solid cancer patients is improved with novel treatment options, the choice of anticoagulation has become a major issue in the management of VTE in this patient population.

The main reason underlying the inferior performance of warfarin in oncology patients is difficult dose titration. Drug interaction and hepatic dysfunction are common in patients on chemotherapy. Frequent interruptions of warfarin for invasive procedures and chemotherapy-induced-thrombocytopenia also lead to fluctuations in anticoagulation level. As a result, highs risk of recurrence of VTE and bleeding were observed in cancer patients taking warfarin. Direct-acting oral anticoagulants (DOACs), on the other hand, may be an attractive alternative treatment to LMWH. They are administered at a fixed dose with predictable pharmacokinetics, so that therapeutic monitoring is not required. There is minimal food and drug interaction. They have been shown to be effective in the treatment of VTE in several pivotal randomized controlled trials in comparison with warfarin . However, their role in malignancy associated VTE is yet to be determined, because cancer patients were either excluded or very much underrepresented in these VTE treatment trials. Moreover, the non-inferiority of DOACs in VTE treatment was only demonstrated against warfarin, which is already shown to be suboptimal in oncology patients. A trial directly comparing DOACs with LMWH in malignancy associated VTE is therefore needed.

Dabigatran etexilate is an oral thrombin inhibitor. It was shown in the RECOVER study to be effective in treatment of VTE and it has a lower bleeding risk than warfarin. It is not metabolized by cytochrome P450 system and therefore, in contrast to other DOACs, concomitant administration of CYP3A4 inducers or inhibitors is not a concern.

We propose this prospective single armed trial to evaluate the efficacy and safety of dabigatran in the treatment of malignancy associated VTE. We will compare the result with our historical control who were treated with LMWH.


Recruitment information / eligibility

Status Recruiting
Enrollment 99
Est. completion date December 31, 2021
Est. primary completion date May 31, 2021
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria:

1. are aged 18 years or above;

2. have acute symptomatic deep vein thrombosis or pulmonary embolism with objective confirmation;

3. have active cancer, which is defined as a diagnosis of cancer other than basal cell or squamous cell carcinoma of skin within six months before enrollment, any treatment for cancer within the previous six months or recurrent or metastatic cancer.

4. Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.

5. Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.

Exclusion Criteria:

1. have Eastern Cooperative Oncology Group (ECOG) performance status score of > 2 at the time of randomization;

2. have life expectancy of less than 3 months;

3. have active bleeding, are at high risk of bleeding, or have contraindications to anticoagulant treatment;

4. receive thrombectomy or fibrinolytic agent to treat the current episode of VTE;

5. receive more than 72 hours pre-treatment with therapeutic dosages of anticoagulant treatment prior to randomization to treat the current VTE episode;

6. are already on long term oral anticoagulation;

7. are on low molecular weight heparin for indications other than VTE;

8. have platelet count of less than 100 x 109/L;

9. are on dual antiplatelet therapy;

10. have a serum creatinine level of more than 220 umol/L or have a calculated creatinine clearance (CrCl) of less than 30 ml/min;

11. have alanine aminotransferase level more than 2 times the upper limit of normal range or cirrhosis;

12. have history of heparin induced thrombocytopenia;

13. are on treatment of potent inhibitors or inducers of P-glycoprotein.

14. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment.

Study Design


Intervention

Drug:
Dabigatran etexilate
Pradaxa 150 mg hard capsules
Tinzaparin
Tinzaparin 175 iu/kg daily will be started after the diagnosis of VTE is confirmed

Locations

Country Name City State
Hong Kong The University of Hong Kong Hong Kong

Sponsors (1)

Lead Sponsor Collaborator
The University of Hong Kong

Country where clinical trial is conducted

Hong Kong, 

Outcome

Type Measure Description Time frame Safety issue
Primary Number of patients with symptomatic VTE first episode of objectively documented symptomatic recurrent VTE (deep vein thrombosis, pulmonary embolism) up to 2 years
Secondary number of mortality, clinically relevant major and non-major bleeding bleeding (major and non-major) and death up to 2 years
See also
  Status Clinical Trial Phase
Recruiting NCT05050617 - Point-of-Care Ultrasound in Predicting Adverse Outcomes in Emergency Department Patients With Acute Pulmonary Embolism
Terminated NCT04558125 - Low-Dose Tenecteplase in Covid-19 Diagnosed With Pulmonary Embolism Phase 4
Not yet recruiting NCT06017271 - Predictive Value of Epicardial Adipose Tissue for Pulmonary Embolism and Death in Patients With Lung Cancer
Completed NCT03915925 - Short-term Clinical Deterioration After Acute Pulmonary Embolism
Completed NCT02502396 - Rivaroxaban Utilization for Treatment and Prevention of Thromboembolism in Cancer Patients: Experience at a Comprehensive Cancer Center
Recruiting NCT05171075 - A Study Comparing Abelacimab to Dalteparin in the Treatment of Gastrointestinal/Genitourinary Cancer and Associated VTE Phase 3
Completed NCT04454554 - Prevalence of Pulmonary Embolism in Patients With Dyspnea on Exertion (PEDIS)
Completed NCT03173066 - Ferumoxytol as a Contrast Agent for Pulmonary Magnetic Resonance Angiography Phase 1
Terminated NCT03002467 - Impact Analysis of Prognostic Stratification for Pulmonary Embolism N/A
Completed NCT02611115 - Optimizing Protocols for the Individual Patient in CT Pulmonary Angiography. N/A
Completed NCT02334007 - Extended Low-Molecular Weight Heparin VTE Prophylaxis in Thoracic Surgery Phase 1/Phase 2
Completed NCT01975090 - The SENTRY Clinical Study N/A
Not yet recruiting NCT01357941 - Need for Antepartum Thromboprophylaxis in Pregnant Women With One Prior Episode of Venous Thromboembolism (VTE) N/A
Completed NCT01326507 - Prognostic Value of Heart-type Fatty Acid-Binding Protein (h-FABP) in Acute Pulmonary Embolism N/A
Completed NCT00780767 - Angiojet Rheolytic Thrombectomy in Case of Massive Pulmonary Embolism Phase 2
Completed NCT00773448 - Screening for Occult Malignancy in Patients With Idiopathic Venous Thromboembolism N/A
Completed NCT00720915 - D-dimer to Select Patients With First Unprovoked Venous Thromboembolism Who Can Have Anticoagulants Stopped at 3 Months N/A
Completed NCT02476526 - Safety of Low Dose IV Contrast CT Scanning in Chronic Kidney Disease Phase 4
Completed NCT00771303 - Ruling Out Pulmonary Embolism During Pregnancy:a Multicenter Outcome Study
Completed NCT00244725 - Odiparcil For The Prevention Of Venous Thromboembolism Phase 2