Long-Term Post Thrombotic Syndrome Assessment (CELEST Long Term). (CELEST-LT)

Determine the Proportion of Patients With Disabling Post Thrombotic Syndrome (Moderate or Severe) in the Long Term Within the Cohort of Patients Who Participated in the Trial CELEST Therapy.

The CELEST Long term is a prospective study, assessing the very long term risk of post thrombotic syndrome (PTS) in patients enrolled in the CELEST double-blind RCT. All patients enrolled in CELEST RCT will benefit from a 7-year follow-up visit conducted over the phone. The primary objective is to assess the proportion of patients with moderate-severe PTS assessed with the patient reported Villalta score and the 2 main secondary objectives are to assess predictors of moderate to severe PTS and the impact of initial compression stockings strength (25mmHg vs. 35mmHg) on the development of moderate-severe PTS. Up to 288 patients may participate.

The investigators believe that this study has the potential to significantly improve the knowledge on the epidemiology of burdensome PTS and on the impact of different initial compression stockings strengths on the risk of PTS.

Study Overview

• Status: Recruiting
• Conditions: Post Thrombotic Syndrome
• Intervention / Treatment: Other: Phone call

Detailed Description

The CELEST double blind RCT demonstrated that 25mmHg elastic compression stockings (ECS) were non inferior to 35mmHg ECS to prevent post thrombotic syndrome (PTS) 2 years after a first proximal deep vein thrombosis (DVT). Likely because of lack of statistical power the investigators were not able to demonstrate that 25mmHg ECS were superior in the overall RCT population and that 35mmHg ECS were superior in patients optimally adherent to ECS. Furthermore, few data are available on the very long term (>5 years).

The CELEST Long term is a prospective study, assessing the very long term risk of PTS in patients enrolled in the CELEST RCT. All patients enrolled in CELEST RCT and willing to participate are eligible and will benefit from a 7-year follow-up visit conducted over the phone.

Primary objective is to assess the proportion of patients with moderate-severe PTS defined as a patient reported Villalta score (PRVS) ≥10 or a venous leg ulcer ipsilateral to index DVT. Secondary objectives include predictors of moderate to severe PTS, impact of initial ECS strength on the development of moderate-severe PTS, impact of anticoagulant treatment (type and duration) on the development of moderate to severe PTS, proportion of PTS (defined as PRVS≥5 or ipsilateral leg ulcer) and impact of PTS on patient's QOL. Study should last 1 year and up to 288 patients may participate.

The investigators believe that this study has the potential to significantly improve the knowledge on the epidemiology of burdensome PTS and on the impact of different initial CE strengths on the risk of PTS.

• Study Type: Observational
• Enrollment (Estimated): 288

Contacts and Locations

• Study Contact: Name: Carole Rolland, MSc; Phone Number: 04 76 76 50 40; Email: carole.rolland@univ-grenoble-alpes.fr
• Study Contact Backup: Name: Alexa Comte, MSc; Phone Number: 04 76 76 50 40; Email: alexa.comte@univ-grenoble-alpes.fr

Study Locations

• France
  • Grenoble, France
    • Recruiting
    • ROLLAND

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients who were enrolled in the CELEST RCT

Description

Inclusion Criteria:

• Patients enrolled and followed in the CELEST RCT*

Exclusion Criteria:

• Patients who withdrew consent or died during the 2-year follow-up of the CELEST RCT.

• Patients who decline or are unable to participate (including severe memory loss issues) to the long-term follow-up

  • CELEST RCT main inclusion/exclusion criteria were: adult (>18 years at time of enrolment) patients first unilateral acute symptomatic proximal lower limb DVT

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
35mmHg ECS; Subjects with first proximal DVT allocated to wear 35 mmHg elastic compression stockings (ECS) for 2 years during the CELEST RCT	Other: Phone call; This follow-up will be conducted over the phone and by mail (some questionnaire may be sent by patient, as per his/her preference)
25mmHg ECS; Subjects with first proximal DVT allocated to wear 25 mmHg elastic compression stockings (ECS) for 2 years during the CELEST RCT	Other: Phone call; This follow-up will be conducted over the phone and by mail (some questionnaire may be sent by patient, as per his/her preference)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with moderate-severe PTS in the whole cohort	PTS defined with the patient reported Villalta score (PRVS). Moderate-severe PTS: PRVS≥10 or presence of a venous leg ulcer in the leg ipsilateral to index DVT The Villalta score consists in 11 questions (5 on subjective symptoms and 6 on objective signs). Each question is coded between 0 and 3 (0: none - 1: mild - 2: moderate - 3: severe). The total score is the sum of the 11 questions and therefore ranges from 0 to 33, where a high value indicates a high level of disability. An additional question asks about the presence of ulcers. If the calculated score is < 15, a value of 15 is assigned to the ulcer score. The thresholds used are as follows: presence of PTS if Villalta ≥ 5; presence of disabling PTS (moderate, severe) if Villalta ≥ 10; presence of severe PTS if Villalta ≥ 15	At the phone follow-up up to 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Predictors of moderate-severe PTS	Predictors of moderate-severe PTS in the whole cohort	Since enrolment in the CELEST CRT
Impact of initial ECS strength on the development of moderate-severe PTS	Comparison of proportion of moderate-severe PTS between patients randomized in the 25mmHg ECS vs. 35mmHg ECS group	Since enrollment in the CELEST study
Impact of initial type of ECS on the development of moderate-severe PTS	Comparison of proportion of moderate-severe PTS between patients who chose to wear above knee vs. below knee ECS during CELEST RCT	Since enrollment in the CELEST study
Impact of adherence to RCT's ECS on the development of moderate-severe PTS	Comparison of proportion of moderate-severe PTS according to adherence to ECS during CELEST RCT	Since enrollment in the CELEST study
Assessment of the use of ECS after the end of the RCT in terms of use, strength, length, adherence, duration	Description of the use of ECS among study participants since the end of their participation in the CELEST RCT	Since enrolment in the CELEST study with focus on the period end of RCT to long-term follow-up
Factors influencing the the decision to continue, stop or resume ECS	Description of the reasons that led to the decision to continue, stop or resume ECS	During the 2-year celest study and during the long-term follow-up
Impact of anticoagulant treatment on the development of moderate-severe PTS	Comparison of proportion of moderate-severe PTS according to type and duration of anticoagulant treatment during CELEST RCT	During the 2-year celest study and during the long-term follow-up
Proportion of patients with any PTS	PTS present if PRVS≥5 or presence of a venous leg ulcer in the leg ipsilateral to index DVT	At the phone follow-up up to 3 months
Predictors of any PTS	Predictors of PTS (defined as a PRVS≥5 or presence of a venous leg ulcer in the leg ipsilateral to index DVT) in the whole cohort	At the phone follow-up up to 3 months
Proportion of patients who developed a serious adverse events (SAE) in the cohort	SAEs assessed are death, venous thromboembolic recurrence, major bleeding and peripheral arterial disease. SAEs are defined according to the International Society on Thrombosis and Haemostasis criteria. These events will be adjudicated by the study adjudication committee	During the 2-year celest study and during the long-term follow-up
Impact of PTS on patients' quality of life	Comparison of QOL scores according to the presence or absence of PTS and its severity; QOL will be assessed using CIVIQ-20 questionnaire	At the phone follow-up up to 3 months

Collaborators and Investigators

• Sponsor: Laboratoires Innothera
• Collaborators: Floralis
• Investigators: Principal Investigator: Jean Luc Bosson, MD, PhD, University Grenoble Alpes, France; Principal Investigator: Jean Philippe Galanaud, MD, PhD, University of Toronto, Canada

Publications and helpful links

General Publications

• Ageno W, Squizzato A, Wells PS, Buller HR, Johnson G. The diagnosis of symptomatic recurrent pulmonary embolism and deep vein thrombosis: guidance from the SSC of the ISTH. J Thromb Haemost. 2013 Aug;11(8):1597-602. doi: 10.1111/jth.12301. No abstract available.
• Utne KK, Ghanima W, Foyn S, Kahn S, Sandset PM, Wik HS. Development and validation of a tool for patient reporting of symptoms and signs of the post-thrombotic syndrome. Thromb Haemost. 2016 Jan;115(2):361-367. doi: 10.1160/th15-04-0318. Epub 2015 Sep 17.
• Kahn SR, Comerota AJ, Cushman M, Evans NS, Ginsberg JS, Goldenberg NA, Gupta DK, Prandoni P, Vedantham S, Walsh ME, Weitz JI; American Heart Association Council on Peripheral Vascular Disease, Council on Clinical Cardiology, and Council on Cardiovascular and Stroke Nursing. The postthrombotic syndrome: evidence-based prevention, diagnosis, and treatment strategies: a scientific statement from the American Heart Association. Circulation. 2014 Oct 28;130(18):1636-61. doi: 10.1161/CIR.0000000000000130. Epub 2014 Sep 22. No abstract available. Erratum In: Circulation. 2015 Feb 24;131(8):e359.
• Launois R, Reboul-Marty J, Henry B. Construction and validation of a quality of life questionnaire in chronic lower limb venous insufficiency (CIVIQ). Qual Life Res. 1996 Dec;5(6):539-54. doi: 10.1007/BF00439228.
• Kaatz S, Ahmad D, Spyropoulos AC, Schulman S; Subcommittee on Control of Anticoagulation. Definition of clinically relevant non-major bleeding in studies of anticoagulants in atrial fibrillation and venous thromboembolic disease in non-surgical patients: communication from the SSC of the ISTH. J Thromb Haemost. 2015 Nov;13(11):2119-26. doi: 10.1111/jth.13140. No abstract available.
• Makedonov I, Kahn SR, Galanaud JP. Prevention and Management of the Post-Thrombotic Syndrome. J Clin Med. 2020 Mar 27;9(4):923. doi: 10.3390/jcm9040923.
• Ten Cate-Hoek AJ. Lower strength stockings: is less better? Lancet Haematol. 2022 Dec;9(12):e865-e866. doi: 10.1016/S2352-3026(22)00266-6. No abstract available.
• Kraaijpoel N, Tritschler T, Guillo E, Girard P, Le Gal G. Definitions, adjudication, and reporting of pulmonary embolism-related death in clinical studies: A systematic review. J Thromb Haemost. 2019 Oct;17(10):1590-1607. doi: 10.1111/jth.14570. Epub 2019 Jul 31.
• Galanaud JP, Genty-Vermorel C, Barrellier MT, Becker F, Jabbour V, Blaise S, Bura-Riviere A, Comte A, Grange C, Guenneguez H, Maufus M, Ouvry P, Richaud C, Rolland C, Schmidt J, Sevestre MA, Verriere F, Bosson JL; CELEST trial investigators. 25 mm Hg versus 35 mm Hg elastic compression stockings to prevent post-thrombotic syndrome after deep vein thrombosis (CELEST): a randomised, double-blind, non-inferiority trial. Lancet Haematol. 2022 Dec;9(12):e886-e896. doi: 10.1016/S2352-3026(22)00247-2.
• Galanaud JP, Genty-Vermorel C, Rolland C, Comte A, Ouvry P, Bertaina I, Verriere F, Bosson JL. Compression stockings to prevent postthrombotic syndrome: Literature overview and presentation of the CELEST trial. Res Pract Thromb Haemost. 2020 Oct 30;4(8):1239-1250. doi: 10.1002/rth2.12445. eCollection 2020 Nov.

Study record dates

Study Major Dates

• Study Start (Actual): July 24, 2023
• Primary Completion (Estimated): October 24, 2023
• Study Completion (Estimated): December 24, 2023

Study Registration Dates

• First Submitted: September 7, 2023
• First Submitted That Met QC Criteria: September 19, 2023
• First Posted (Actual): September 21, 2023

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 19, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Post thrombotic syndrome; long-term follow-up; Deep vein Thrombosis; Elastic compression stockings
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Disease; Embolism and Thrombosis; Venous Thrombosis; Thrombosis; Peripheral Vascular Diseases; Venous Insufficiency; Phlebitis; Syndrome; Postthrombotic Syndrome; Postphlebitic Syndrome
• Other Study ID Numbers: 2023-A00528-37

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Relevant deidentified participant data (with a data dictionary) will be available to other researchers on reasonable request after publication, approval from both principal investigators and sponsor, and after a data access agreement is signed

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No