Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03572036 |
| Other study ID # |
999918109 |
| Secondary ID |
18-H-N109 |
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
June 20, 2018 |
| Est. completion date |
April 16, 2021 |
Study information
| Verified date |
April 2021 |
| Source |
National Institutes of Health Clinical Center (CC) |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Background:
Sickle cell disease (SCD) is a common inherited blood disorder. Many people with SCD are at
risk to get pulmonary hypertension (PH). PH means that the blood pressure in the blood
vessels to the lungs is high, and is a serious disease and. Very few studies have looked at
the success of treatments for PH in people with SCD. Researchers want to learn more about
treating PH with a type of drug called phosphodiesterase type 5 inhibitors (PDE5-I). They
will look at the records of people who have already joined other studies.
Objective:
To identify people who already joined NIH SCD protocols whose medical records should be
reviewed. The review will look at the description of SCD patients with PH who have already
taken PDE5-I and the outcomes for these people.
Eligibility:
Adults ages 18 and older with SCD and PH. They must have joined certain NIH studies and taken
PDE5-I therapy for at least 16 weeks.
Design:
This study is a review of medical records.
Researchers will collect data from databases of existing studies. They will identify people
in those studies who have SCD and PH and took the study drug for at least 16 weeks.
Researchers will review the full medical records of those people.
From that review, researchers will find participants who meet the inclusion criteria. They
will extract data from those records.
Researchers will analyze the data. This includes results from heart and lung tests, imaging,
and walking tests. It will also include results of a procedure called right heart
catheterization.
Demographic data and lab data will also be collected.
Researchers will remove identifying information from the data, then share it in a database.
Description:
There is a lack of evidence-based treatment for patients with sickle cell disease (SCD) with
pulmonary hypertension (PH). PH is a leading cause of mortality in SCD and is an independent
risk factor for mortality in this population. SCD is a major health problem worldwide,
primarily affecting people of African descent. In the United States approximately 100,000
individuals have SCD and 0.2% of African Americans have homozygous SS sickle cell disease,
while 8% of African Americans carry one allele and have sickle cell trait. In developed
countries, even in the current era of hydroxyurea, SCD patients have relatively shortened
lifespans with a median life expectancy of approximately 48 years for females and 42 years
for males.
PH affects up to 1/3 of adults screened by echocardiography and pre-capillary PH is diagnosed
in 6% by right heart catheterization (RHC). Data suggest that either precapillary or
post-capillary PH in SCD are associated with a 5-fold risk of early mortality, and SCD
subjects with echocardiographic signs of both have a 13-fold risk of early mortality. Though
a cause and effect relationship between the presence of PH and early mortality in adult
subjects with SCD has not been conclusively established, data regarding the causes of death
in a prospective observational study of adult SCD patients suggest that cardiopulmonary cause
of death was present in at least 35% of patients.
The World Health Organization (WHO) reclassified SCD-related PH as Group 5 in 2013.
Therefore, SCD-related PH is not eligible for vasodilator therapies currently available for
WHO Group 1 pulmonary arterial hypertension (PAH). There have only been three prospective
clinical trials of vasodilator therapies in sickle cell patients with RHC-defined PH. After
the findings of the Walk-PHaSST study were reported, a strong recommendation against
sildenafil in sickle cell patients with PH was made in guidelines published by the American
Thoracic Society in 2014. However, a major limitation of the trial was that, in order to
improve trial feasibility, subjects were eligible for enrollment based on an elevated TRV, as
well as RHC-defined PH, leading to incomplete hemodynamic characterization of study patients.
The physiologic understanding of the differences between subjects who developed SAEs and
those who tolerated sildenafil remains poorly understood. In individual circumstances, some
patients may have chosen to continue sildenafil. If some patients with SCD-related PH have
continued to benefit from sildenafil therapy in the time since this clinical trial was
reported, it would raise the question of whether a subgroup of SCD-related PH patients may
still benefit from PDE5-Is and how these patients could be clinically characterized.
Given the difficulty of enrolling SCD-related PH patients into prospective, multi-center
trials, for example as demonstrated by the ASSET trials being closed due to low enrollment,
we plan to utilize existing clinical data available on patients who were documented to have
RHC- defined PH prior to initiation of PDEI-5 therapy, in order to better characterize the
use of this medication in patients with SCD-related PH.
