NCT01553981

Brief Summary

Systemic sclerosis (SSc, scleroderma) is a multisystem autoimmune rheumatic disease that causes inflammation, vascular damage and fibrosis. Besides involvement of skin, fibrosis also affects lung and heart. Although advances in understanding in pathophysiology and use of immunosuppressive therapy has brought significant improvement in outcome of other autoimmune diseases, scleroderma still remains as a disease with high mortality and 10 yr survival rate has improved only from 54% to 66% during last 25 years1. The frequency of deaths due to renal crisis significantly decreased (mainly due to effectiveness of ACE Inhibitors), from 42% to 6% of scleroderma-related deaths (p 0.001), whereas the proportion of patients with scleroderma who died of pulmonary fibrosis increased (due to lack of significant treatment) from 6% to 33% (p 0.001). However, presently, trials with immunosuppressive drugs including cyclophosphamide and other targeted molecules like Bosentan and Imatinib mesylate have shown very modest results at the best and given the risk of toxicity. The investigators have conducted three clinical trials with PDE5 inhibitor Tadalafil in the refractory Raynaud's phenomenon (RP) in SSc over last 3 years and had found good response in RP, healing of digital ulcers, prevention of new digital ulcers and also observed improvement in skin tightening, endothelial dysfunction and improvement of quality of life. The investigators therefore hypothesize that tadalafil may have an efficacy in improving the ILD of SSc. The investigators therefore design this double-blind, randomized, placebo-controlled trial of oral Tadalafil (20 mg alternate day) in patients with SSc having ILD. Patients will be randomly assigned in a 1:1 ratio to receive either Tadalafil or matched placebo and will be followed up for 6 months. Prednisolone (if required for indications other than ILD) will be allowed up to 10 mg/d in all patients. Patient/s requiring more than 10 mg/d of prednisolone or equivalent dose of steroid will be excluded from the study. Patients who will fail on therapy during the study will be excluded from the study and will be asked to choose any therapeutic option from the rescue protocol. Patients with FVC ≤ 70% predicted or DLCO ≤ 70 % of predicted, Evidence of ILD on HRCT will be enrolled. The primary objective of the study will be the change in FVC (expressed as a percentage of the predicted value) from baseline values at the end of 6-months of treatment. The secondary objectives will be improvement in dyspnea, improvement in 6 min walk distance, change in DLCO, change in total lung capacity, change in the disability index of the Health Assessment Questionnaire (S HAQ), and change quality of life (SF-36), levels of NT pro-BNP and fibrosis markers.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
40

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Mar 2012

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 2012

Completed
10 days until next milestone

First Submitted

Initial submission to the registry

March 11, 2012

Completed
3 days until next milestone

First Posted

Study publicly available on registry

March 14, 2012

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2014

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2014

Completed
Last Updated

April 21, 2015

Status Verified

April 1, 2015

Enrollment Period

2.1 years

First QC Date

March 11, 2012

Last Update Submit

April 20, 2015

Conditions

Lung Diseases, Interstitial

Keywords

Interstitial lung diseaseScleroderma

Outcome Measures

Primary Outcomes (1)

  • Change in FVC (expressed as a percentage of the predicted value)

    To assess the change in FVC (expressed as a percentage of the predicted value) from baseline values at the end of 6 months

    6 months

Secondary Outcomes (6)

  • Improvement in dyspnoea (as measured by Mehler dyspnoea index)

    6 months

  • Improvement in 6 min walk test

    6 months

  • change in DLCO

    6 months

  • change in total lung capacity

    6 months

  • change in the disability index of the Health Assessment Questionnaire (S HAQ)

    6 months

  • +1 more secondary outcomes

Study Arms (2)

Tadalafil

ACTIVE COMPARATOR

Tablet Tadalafil 20 mg every alternate day

Drug: Tadalafil

Placebo

PLACEBO COMPARATOR

Tablet Placebo every alternate day

Drug: Placebo

Interventions

TadalafilDRUG

Tab. Tadalafil 20 mg every other day for 6 months

Tadalafil
PlaceboDRUG

Shape , size, color and odor matched Tab. of inert material every other day for 6 months

Placebo

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Fulfillment of the criteria for systemic sclerosis (SSc) by American College or Rheumatology (ACR) criteria (Subcommittee for Scleroderma Criteria, 1980)
  • Forced vital capacity (FVC) ≤ 70% predicted.
  • DLCO ≤ 70 % of predicted
  • \. Presence of dyspnea on exertion (grade 2 on the Magnitude of Task component of the Mahler Modified Dyspnea Index) 4. Evidence of ILD on HRCT

You may not qualify if:

  • Those that cannot perform PFT or 6 min walk test
  • High dose prednisolone (1 mg/kg) or cyclophosphamide (\> 500 mg) or MMF (\> 500mg/d) or (azathioprine \> 1 mg/kg) for more than 4 weeks anytime within previous 6 months
  • SBP \< 90 mmHg or history of orthostatic hypotension
  • Current smokers
  • Women who are pregnant or lactating
  • Those receiving nitrates, alpha blockers, or both, other phosphodiesterase inhibitors
  • Current use of captopril (because of sulfhydryl group). If ACE- inhibitors are indicated, an ACE-inhibitor other than captopril should be used.
  • Serum creatinine ≥ 2.0 mg/dl.
  • Obstructive lung disease (FEV1/FVC ratio \< 0.6)
  • Prostacyclins or endothelin antagonists or who had received any investigational drug within the prior month
  • Acute coronary or cerebrovascular event within 3 months
  • Evidence of malignancy
  • Peptic ulcer
  • Hepatic dysfunction.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

SGPGIMS

Lucknow, Uttar Pradesh, 226014, India

Location

MeSH Terms

Conditions

Lung Diseases, InterstitialScleroderma, Diffuse

Interventions

Tadalafil

Condition Hierarchy (Ancestors)

Lung DiseasesRespiratory Tract DiseasesScleroderma, SystemicConnective Tissue DiseasesSkin and Connective Tissue DiseasesSkin Diseases

Intervention Hierarchy (Ancestors)

CarbolinesPyridinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsIndole AlkaloidsIndolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds, 3-Ring

Study Officials

  • Vikas Agarwal, MD, DM

    SGPGIMS

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER GOV
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Additional Professor

Study Record Dates

First Submitted

March 11, 2012

First Posted

March 14, 2012

Study Start

March 1, 2012

Primary Completion

April 1, 2014

Study Completion

May 1, 2014

Last Updated

April 21, 2015

Record last verified: 2015-04

Locations

IN(1)