to assess the effects of BPA on quality of life and exercise capacity in a group of symptomatic CTEPD patients without PH with incomplete recovery after three month of rehabilitation.
ID
Source
Brief title
Condition
- Pulmonary vascular disorders
- Embolism and thrombosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome is the effect of BPA on the improvement of disease specific
quality of life (PEmb-Qol) between the study groups, 6 months after
randomization.
Secondary outcome
secondary outcomes include physical performance and endurance measured by the
cardiopulmonary exercise test (CPET) and constant Work Rate cycle Test (CWRT),
NYHA class and modified BORG scales before and after cardiopulmonary exercise
tests at baseline 6 and 12 months following randomization.
Furthermore PROMS for functional status (post VTE functional scale), anxiety
and depression (hospital anxiety and depression scale (HADS), work productivity
(Work Productivity and Activity Impairment) and generic QoL (EQ-5D-5L), at
baseline and after 6,12 and 24 months following randomization. Additionally,
incidence of serious advers events will be evaluated.
Background summary
Up to 50% of acute pulmonary embolism (PE) patients report persistent dyspnea
and/or functional limitations despite anticoagulation therapy (1, 2).
Persistent dyspnea and functional limitations may relate to incomplete thrombus
resolution, which cause perfusion defects and by that impairing gas exchange
and reducing ventilatory efficiency (6-8). These long-term complications of PE
have a major impact on quality of life and has been associated with higher
risks of depressive disorders, unemployment, social isolation and excess health
care costs (2).
Incomplete thrombus resolution occurs in approximately 30-50% after 3-6 months
of anticoagulant treatment (3,4), while chronic thromboembolic pulmonary
hypertension (CTEPH), the most serious long-term complication of acute PE,
develops in only 2-4% of PE survivors (5). In the absence of PH at rest, this
condition is referred to as chronic thromboembolic pulmonary disease (CTEPD)
without PH at rest (6-8). Recently, the hemodynamic definition of CTEPH has
been updated and expanded (9). The cut-off values for the mean pulmonary artery
pressure (mPAP) is lowered from >25 to 20mmHg and for the pulmonary vascular
resistance (PVR)form > 3 to > 2.0 Woods units (WU). However although these new
cut-off values might better reflect de limits of normal ranges, the new cut-off
ranges do not yet translate into new therapeutic recommendations since the
efficacy of therapy on patients with a mPAP 21-24mmHg or PVR 2-3 WU are still
unknown.
Therapeutic options that are well investigated in patients with the former
definition of CTEPH are either surgical removal of the chronic thrombi
(pulmonary endarterectomy [PEA]), balloon pulmonary angioplasty (BPA) or PH
specific medication (6,9). For the patients with a mPAP < 25,,Hg and PVR < 3,
and thus for the majority of patients with functional limitations following
acute PE, there is no established therapy yet. Neither is the exact incidence
and prevalence and impact on the long-term of CTEPD without PH well known as
follow-up studies in which acute PE patients were subjected to repeated imaging
tests plus quality of life questionnaires and functional tests are unavailable.
However, as with CTEPH with mPAP > 25mmHg and PVR > 3WU (6,9), case series
suggest that both BPA and PEA has beneficial effects on hemodynamic and gas
exchange parameters in CTEPD patients with mPAP < 25mmHg (10-12). However, PEA
is quite invasive and carries a substantial peri-procedural risk (13). Since
CTEPD with mPAP < 25mmHg and PVR < 3WU have a better prognosis compared to
those with mPAP > 25mmHg and PVR > 3WU, a less invasive procedure would be
preferred.
Regarding BPA, two recent, small retrospective studies have suggested BPA is
a safe and effective alternative treatment in CTEPD with mPAP < 25mmHg and PVR
< 3WU (11,12). Wiedenroth and colleagues (11) performed 35 BPA interventions in
10 consecutive CTEPD patients without PH according the former definition, with
significant improvement of WHO functional class, 6-minute walk distance (6MWD)
and Borg score. These benefits came at the price of one mild parenchymal
bleeding, resulting in hemoptysis. Secondly, Inami et al (12) reported on 15
CTEPD patients without PH, according the former definition, who safely
underwent BPA, improvement of exercise tolerance. The median number of BPA
sessions was 2 (IQR 1-3), and the median number of vessels treated per patient
was 9 (IQR 5-15), which is a lower number of sessions compared to what is
routine in CTEPH. No occurrences of reperfusion or pulmonary injuries across
the sessions were detected after six months of follow-up. Based on these
results, BPA is regarded as a potentially effective treatment of CTEPD without
PH.
We aim to evaluate the effect of BPA in CTEPD patients without PH or with
mild PH (mPAP < 25mmHg and PVR < 3WU) on patients reported symptoms, including
quality of life, and pulmonary vascular responses to exercise. Because the
recovery of exercise intolerance after acute PE may also occur spontaneously
(whether or not from further resolution of perfusion defects) and definitely
improves after pulmonary rehabilitation, we designed a randomized controlled,
cross-over trial to assess the benefit from BPA after at least three months of
anticoagulation and three months of pulmonary rehabilitation.
Study objective
to assess the effects of BPA on quality of life and exercise capacity in a
group of symptomatic CTEPD patients without PH with incomplete recovery after
three month of rehabilitation.
Study design
Mono-center, randomized controlled, open label clinical trial, with an
cross-over part and a 6, 12 and 24 month follow-up
Intervention
All patients are subjected to balloon pulmonary angioplasty (BPA); patients who
will be first randomized to the BPA arm will undergo BPA sessions the first six
months and followed by six to 12 months with no intervention and vice versa:
patients who will be randomized to the expectative treatment arm first, will be
followed the first six months and undergo BPA six to 12 months following the
randomization
Study burden and risks
All patients will be subjected to BPA. Patients are admitted for one day for
each BPA session. The study intervention will therefore ask a considerable
effort from the patient. In two case series of BPA, including in total 25 CTEPD
patients without PH with a median of 2-4 BPA sessions, was one mild bleeding
reported (1,2). No other adverse events were reported. Overall, the risk of
(serious) adverse events in this study is considered as low, based on an
unlikely risk of moderate impact due to one of the exercise tests, and an
moderate risk on low or moderate risk of the due to the BPA. Patients
randomised to the control arm will be asked not to engage in further
rehabilitation and to resume their usual physical activity.
de Boelelaan 1117
Amsterdam 1081 HV
NL
de Boelelaan 1117
Amsterdam 1081 HV
NL
Listed location countries
Age
Inclusion criteria
1. Diagnosis of CTEPD without or with only mild PH (mPAP < 25mmHg and PVR <
3WU), confirmed by a multidisciplinary team of CTEPD/CTEPH experts, based on:
-acute PE that was objectively diagnosed at least 3 months prior to inclusion
and adequately treated
-persistent functional limitations: (New York Heart Association (NYHA) class
>=2)
-persistent radiological perfusion defects, on any adequate perfusion imaging
method: >= 3 segmental perfusion defects
-CPET result with:
a) at least 2 of the following criteria:
• peak VO2 < 80%;
• peak O2 pulse < 80% of predicted;
• V*E/V*CO2 @ nadir > 34;
• Vd/Vt increasing until peak exercise or peak Vd/Vt > 0;4;
• gradual drop of SpO2 of >= 3%;
b) these exercise findings cannot be explained otherwise
2. patients completed a pulmonary rehabilitation program of at least 8 weeks no
longer than 2 months before randomization. Depending on the local protocol,
sessions could be daily or a few times a week
3. qualifying symptom limited CPET and CWRT were performed after the pulmonary
rehabilitation program
4. age 18-80 years
5. Clinical Frailty Scale (CFS) score < 5 (CFS is a 9-point scale that
summarizes the overall level of fitness or frailty of an older adult)
6. written informed consent
7. prior treatment or restart with a therapeutic dose of anticoagulation
treatment before randomization
Exclusion criteria
1. history of BPA or PEA
2. residual thrombi that are not eligible for BPA, as concluded by the
(intervention) radiologists,
3. major acute or chronic cardiopulmonary comorbidities with an expected impact
on survival, exercise capacity and/or gas exchange, e.g. significant coronary
heart disease, diastolic/systolic heart failure, pulmonary hypertension (mPAP >
25 mmHg), severe chronic obstructive pulmonary disease (COPD) GOLD class >=3,
interstitial lung disease (ILD), disabling neuromuscular disease, malignancy
4. inability to undergo exercise tests
5. contrast allergy
6. creatinine clearance < 30ml/min
7. pregnancy or breastfeeding
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL83240.018.23 |