Haemoptysis Clinical Trial
Official title:
The Utility of External Beam Radiotherapy for Haemoptysis Secondary to Aspergillomata and Structural Lung Diseases in Patients Who Are Refractory to Medical Management and Not Surgical Candidates: A Pilot Study
The sequelae of tuberculosis are still the commonest causes of haemoptysis in the developing world, where life-threatening haemoptysis remains a common and not infrequently fatal medical emergency. Haemoptysis can be life-threatening either as a result of compromised gas exchange or because of circulatory collapse secondary to acute blood loss. Haemodynamic and ventilatory support, followed by bronchial artery embolisation (BAE) as a bridge to potentially curative treatment such as lung resection, remains the standard of care. Often patients do not qualify for surgical intervention and BAE is, at best, a temporary solution. External beam radiotherapy (EBRT) may be an alternative, curative intervention in the management of haemoptysis in patients with no alternative options. There is a paucity of studies reporting the use of EBRT in patients without malignancy and with regards to specific doses of EBRT. This pilot study aims to explore the potential of varying doses of EBRT in the management of massive haemoptysis.
Currently the best curative treatment of massive haemoptysis is surgical resection of the
affected portion of lung. For patients who do not qualify for surgery, there are few
alternative interventions, most of which only provide a temporary solution.
Surgical resection of the diseased areas, which offers the possibility of cure, is best
performed as an elective procedure. It carries a not insignificant mortality, with reports
varying between 1% and 50%. Unfortunately, many patients admitted to Tygerberg Academic
Hospital, are not candidates for either elective or emergency surgical resection. The most
common reasons for inoperability are: irresectable disease (i.e. damage to the lungs is
bilateral and too extensive to allow resection, or the site of bleeding is not known); or
severely reduced cardiopulmonary reserves secondary to extensive pre-existing lung damage,
making lung resection surgery impossible due to excessively high mortality risk.
Repeat BAE (as a palliative measure in inoperable cases) is not always technically feasible
and does not always lead to cessation of the bleeding. Additionally long term recurrence
rates following BAE are variable estimated at between 18-42%, and carries a high mortality.
A significant number of patients with massive haemoptysis do not qualify for either surgery
or BAE, thus rendering them without treatment option, save palliation with long-term opiates.
Their fate is that of recurrent haemoptysis and a high associated mortality. Endobronchial
occluding devices have been considered, however their high cost and required expertise
prohibits their extensive use.
A novel treatment of this condition potentially is external beam radiotherapy (EBRT). A case
report of five patients has documented EBRT in the setting of mycetoma where between 7 and
14Gy was used, with cessation of life threatening haemoptysis. However follow-up was limited
to 6 months, and the effects of EBRT in the setting of post-tuberculous structural lung
disease without mycetoma is not known. The potential mechanism of the achieved haemostasis
was speculated as being the induction of radiation damage to the radiosensitive capillaries,
with subsequent inflammatory response, in keeping with previous rat models of lung perfusion
following high dose (30Gy) EBRT exposure.
There is therefore a paucity of data on the utility of EBRT in benign conditions such
bronchiectasis and aspergillomata. Furthermore due to the different effects, particularly
temporal, the radiation has on normal and benign conditions it is difficult to extrapolate
from the malignant scenario to the benign. Laboratory studies have however demonstrated the
effects of high dose radiation on tissue that may result in a reduced bleeding tendency.
This study aims to explore a novel therapeutic strategy for patients with life-threatening
haemoptysis who are not candidates for definitive management (i.e. lung resection). This
study also aims to establish if there is a measurable response to varying doses of chest
radiation in cases of haemoptysis caused by benign conditions.
This study is a prospective randomised control-intervention study. Patients will be allocated
to one of 2 arms (control and EBRT at 3.5Gy weekly for 5 fractions to a maximum of 17G). The
primary outcome will be time to recurrent haemoptysis. Secondary outcomes include physical
performance, lung function and the occurrence of EBRT complications. Patients will be
followed up daily whilst in hospital and for one year post intervention.
Assessors and those performing the statistical analysis will be blinded to the group
allocation. Statistical analysis will include univariate and multivariate analysis with
appropriate parametric or non-parametric tests. Appropriate tests for categorical data (e.g.
Chi-squared test) and continuous data (e.g. Kruskal-Wallis, and ANOVA) will be used. Logistic
and linear regression modelling will be used for certain outcomes, and multivariate analysis
will be performed using step-wise regression modelling and full modelling where appropriate.
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| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Recruiting |
NCT02913365 -
Etiologies, Investigations and Outcomes of Patients Presenting With Hemoptysis
|
N/A | |
| Not yet recruiting |
NCT02816229 -
Endobronchial Valves in Inoperable Patients With Haemoptysis
|
N/A |