Trial Information

An Observational, Long-Term Follow-up Study of Eligible Individuals Declining To Participate in the Scleroderma Cyclophosphamide or Transplantation (SCOT) Study

For multiple reasons, the SCOT investigators and the sponsor of the SCOT trial, the Division
of Allergy, Immunology, and Transplantation (DAIT) of the National Institute of Allergy and
Infectious Diseases (NIAID), determined that it is important to track the course of a
'matched' group of patients, who are not exposed to these treatments but receive currently
available therapy in the community. First, such a group will provide information to
determine if the SCOT entry criteria do indeed identify these high-risk individuals. More
importantly, such a group of patients is likely to be treated with a variety of medical
regimens, including some immunosuppressive therapy with cyclophosphamide or other
immunosuppressive agents that may modify the natural history of the disease. In evaluating
the relative efficacy of the two treatment regimens, it will be important to assess whether
outcomes in the subjects treated under the SCOT protocol have outcome profiles that differ
from those associated with the matched group of patients treated in the community. One
readily available group that meets these criteria are those individuals who are otherwise
eligible for the SCOT trial but fail to be randomized because they either decline to
participate or are denied insurance coverage to receive the SCOT treatment regimens.

The duration of this trial is 44 months. Participants will be enrolled over the same period
as the SCOT trial. Participants will follow the course of treatment prescribed by their
treating physician with no interference from the registry. All participant contact,
including obtainment of informed consent and telephone interview regarding outcome
measurements will be performed by SCOT study personnel at the University of Texas, Houston
(one of the SCOT transplant centers). Participants will be contacted by phone every 3 months
to determine vital status, record medical and other therapy, and administer the modified
Scleroderma Health Assessment Questionnaire (S-HAQ). Medical records will be obtained to
verify self-reported medical events.

The primary outcomes of interest include: death, renal failure requiring dialysis, and
pulmonary compromise requiring oxygen, pulmonary hypertension requiring treatment. In
addition the following will be recorded: medical therapies and procedures (including
hospitalizations), scleroderma renal crisis, and functional status as determined by the
modified Scleroderma Health Assessment Questionnaire.

The primary endpoint for this study, which is designed to be similar to the endpoint for the
SCOT study, is event-free survival (EFS) at 44 months after subject enrollment. The events
will be defined as any one of the following:

1. Death.

2. Respiratory failure defined as the need for supplementary oxygen; or

3. Renal failure, as defined by chronic dialysis > 6 months or renal transplantation.

The secondary endpoints include:

1. Mortality

2. Medical therapy

3. Occurrence of scleroderma renal crisis with outcome (dialysis requiring or not)

4. Diagnosis and treatment for pulmonary hypertension;

5. Need for hyperalimentation;

6. Amputation whether surgical or auto-amputation

7. Modified Scleroderma Health Assessment Questionnaire (m-HAQ/S-HAQ);

8. Hospitalization or surgery.