Study and intervention details | Baseline characteristics | Outcomes | Risk of bias (selection bias) |
---|---|---|---|
Pharmacological agents | |||
Azathioprine | |||
Raghu et al. 1991 [21] | Mean Age: 56 years | Primary outcomes: not stated as primary or secondary: measurable change in lung function (FVC, DLCO, P[A-a]O2) at 12 months; survival | Unclear risk |
Country: USA | M/F%: 55/45 | ||
Design: RCT | Time since diagnosis: 2 years | ||
Number of centres: 2 | FVC: 67% | ||
Funding: Grant from Virginia Mason ResearchCentre, Seattle, USA | Length of follow-up: 12 months | ||
Interventions: | |||
1. Prednisone and placebo, n = 13 | |||
2. Prednisone and azathioprine, n = 14 | |||
Duration of treatment: 12 months | |||
BIBF-1120 | |||
Richeldi et al. 2011 [22] | Mean Age: 65 years | Primary outcomes: annual rate of decline in FVC | Low risk |
Country: 25 countries including Italy, Mexico, | M/F%: 75/25 | ||
Germany, USA, Korea, UK, France. | Time since diagnosis: 1.2 | Secondary outcomes: % predicted FVC; DLCO; SpO2; TLC; 6MWT, SGRQ, decrease in FVC of more than 10% or more than 200 ml; SpO2 decrease of more than 4%; acute exacerbations; survival; death from a respiratory cause; adverse events | |
Design: RCT (dose finding phase II study) | years | ||
Number of centres: 92 | FVC: 80% | ||
Funding: supported by Boehringer Ingelheim | |||
Interventions: | |||
1. BIBF 1120 50 mg/day, n = 86 | |||
2. BIBF 1120 50 mg twice per day (100 mg/day), n = 86 | Length of follow-up: 54 weeks | ||
3. BIBF 1120 100 mg twice per day (200 mg/day), n = 86 | |||
4. BIBF 1120 150 mg twice per day (300 mg/day), n = 85 | |||
5. Placebo, n = 85 | |||
Duration of treatment: 52 weeks | |||
N-Acetylcysteine (alone or in combination) | |||
Demedts et al. 2005 [18] | Mean Age: 63 years | Primary outcomes: absolute changes in VC and DLCO at 12 months | Low risk |
Country: Belgium, France, Germany, Italy, Spain, the Netherlands | M/F%: 72/28 | ||
Design: RCT | Time since diagnosis: 1.6 years | Secondary outcomes: % predicted VC, % predicted DLCO, alveolar volume change and % predicted, CRP score, dyspnoea score, maximum exercise indexes, HRCT outcomes, SGRQ, adverse events, withdrawals, and mortality | |
Number of centres: 36 | FVC: 66% | ||
Funding: sponsored by the Zambon group | |||
Interventions: | |||
1. N-acetylcysteine, prednisolone, azathioprine, n = 92 (80 analysed) | |||
2. Placebo, prednisolone, azathioprine, n = 90 (75 analysed) | Length of follow-up: 12 months | ||
Duration of treatment: not stated, assume 12 months. | |||
Raghu et al., (IPFCRN) 2012 [19] | Mean Age: 68 years | Primary outcomes: change in FVC at 60 weeks | Low risk |
Country: USA | M/F%: 75/25 | ||
Design: RCT (PANTHER study) | Time since diagnosis: 1 year | Secondary outcomes: rate of death, time until death, frequency of acute exacerbation, frequency of maintained FVC response, time to disease progression, clinical and physiological measures including: DLCO, 6MWT, CPI, UCSD SBQ, SGRQ, SF-36, EQ-5D. Adverse events. | |
Number of centres: 25 | FVC: 71% | ||
Funding: grants from the NHLBI; the Cowlin Family fund. NAC and placebo donated by Zambon | |||
Interventions: | |||
1. N-acetylcysteine and placebo (data not presented in article as ‘ongoing’ data collection), n = 81 | |||
2. N-acetylcysteine/prednisolone/azathioprine, n = 77 | Length of follow-up: 60 weeks in the planned analysis. The study was stopped early. The mean follow-up was 32 weeks. | ||
3. Placebo, n = 78 | |||
Duration of treatment: up to 60 weeks | |||
Homma et al. 2012 [20] | Mean Age: 68 years | Primary outcomes: absolute change in FVC at 48 weeks | Unclear risk |
Country: Japan | M/F%: 76/24 | ||
Design: RCT | Time since diagnosis: 3 years | ||
Number of centres: 27 | FVC: 89% | Secondary outcomes: changes in lowest aterial O2 saturation, 6MWT distance, PFT parameters (VC, % predicted VC, TLC, % predicted TLC, DLCO, predicted DLCO), serum markers of pneumocyte injury; disease progression as determined by HRCT; subjective changes in symptoms such as dyspnoea, adverse events. | |
Funding: grant from Ministry of Health, Labour and Welfare | |||
Interventions: | |||
1. N-acetylcysteine inhaled, n = 51 (38 analysed) | |||
2. Control, n = 49 (38 analysed) Duration of treatment: 48 weeks | |||
Length of follow-up: 48 weeks | |||
Pirfenidone | |||
Noble et al., 2011 [15] | Mean Age: 67 years | Primary outcomes: change in per cent predicted FVC | Low risk |
Capacity study 006 | M/F%: 72/28 | ||
Country: Australia, Belgium, Canada, France, Germany, Ireland, Italy, Mexico, Poland, Spain, Switzerland, UK, USA | Time since diagnosis: ≤1 | ||
year: 59% | Secondary outcomes: categorical FVC (5-point scale), progression-free survival, worsening IPF, dyspnoea, 6MWT distance, worst peripheral oxygen saturation (SpO2) during the 6MWT, per cent predicted DLco, fibrosis, mortality. | ||
FVC: 74% | |||
Design: RCT | |||
Number of centres: 110 centres | |||
Funding: InterMune | |||
Interventions: | |||
1. Pirfenidone 2403 mg/day, n = 171 | Length of follow-up: 72 weeks from the date the last patient was enrolled. | ||
2. Placebo, n = 173 | |||
Duration of treatment: 72 weeks | |||
Noble et al., 2011 [15] | Mean Age: 66 years | Primary outcomes: change in per cent predicted FVC | Low risk |
Capacity study 004 | M/F%: 71/29 | ||
Country: Australia, Belgium, Canada, France, Germany, Ireland, Italy, Mexico, Poland, Spain, Switzerland, UK, USA | Time since diagnosis: ≤1 | ||
year: 48% | Secondary outcomes: categorical FVC (5-point scale), progression-free survival, worsening IPF, dyspnoea, 6MWT distance, worst peripheral oxygen saturation (SpO2) during the 6MWT, per cent predicted DLco, mortality. | ||
FVC: 75% | |||
Design: RCT | |||
Number of centres: 110 centres | |||
Funding: InterMune | |||
Interventions: | |||
1. Pirfenidone 2403 mg/day, n = 174 | Length of follow-up: 72 weeks from the date thelast patient was enrolled | ||
2. Pirfenidone 1197 mg/day, n = 87 | |||
3. Placebo, n = 174 | |||
Duration of treatment: 72 weeks | |||
Taniguchi et al., 2010 [16] | Mean Age: 65 years | Primary outcomes: change in vital capacity to week 52 | Unclear risk |
Country: Japan | M/F%: 78/22 | ||
Design: RCT | Time since diagnosis: <1 | ||
Number of centres: 73 | year: 37% | Secondary outcomes: Progression-free survival time, change in lowest SpO2 during the 6MET. Pa,O2, PA-a,O2, TLC and DLCO, acute exacerbation, markers of interstitial pneumonias, symptoms. | |
Funding: public sector grants. Drug and placebo from Shionogi & Co, Ltd. | FVC: 78% | ||
1. Pirfenidone 1800 mg/day, n = 108 | |||
2. Pirfenidone 1200 mg/day, n = 55 | |||
3. Placebo, n = 104 | Length of follow-up: 52 weeks | ||
Duration of treatment: 52 weeks | |||
Azuma et al., 2005 [17] | Mean Age: 64 years | Primary outcomes: change in the lowest SpO2 during the 6MET | Unclear risk |
Country: Japan | M/F%: 90/10 | ||
Design: RCT | Time since diagnosis: <1 | ||
Number of centres: 25 | year: 22% | Secondary outcomes: resting PFTs while breathing air (VC, TLC, DLCO PaO2), disease progression by HRCT patterns, acute exacerbation, serum markers of pneumocyte damage, QoL | |
Funding: Shionogi & co, Ltd | FVC: 80% | ||
Interventions: | |||
1. Pirfenidone 1800 mg/day, n = 73 | |||
2. Placebo, n = 36 | |||
Duration of treatment: 9 months | |||
Length of follow-up: minimum of 9 months | |||
Thalidomide | |||
Horton et al., 2012 [24] | Mean Age: 68 years | Primary outcomes: cough-specific quality of life (CQLQ) | Low risk |
Country: USA | M/F%: 78/22 | ||
Design: randomised cross-over trial | Time since diagnosis: 1.7 | ||
Number of centres: one | years | Secondary outcomes: cough, respiratory quality of life. | |
Funding: Celgene Corporation | FVC: 70% | ||
Interventions: | |||
1. Thalidomide, n = 23 | Method of assessing outcome: Cough-specific quality of life measured by CQLQ. Cough measured by 10 cm VAS. Respiratory quality of life measured by SGRQ. | ||
2. Placebo, n = 23 | |||
Duration of treatment: 12 weeks each treatment with a 2 week washout period between treatments. | |||
Length of follow-up: 12 weeks. | |||
Sildenafil (severe IPF) | |||
Zisman and colleagues IPFCRN, 2010 [23] | Mean Age: 69 years | Primary outcomes: presence or absence of an improvement of at least 20% in the 6MWT distance at 12 weeks. | Unclear risk |
Country: USA | M/F%: 84/16 | ||
Design: RCT | Time since diagnosis: 1.9 | ||
Number of centres: 14 | years | ||
Funding: NHLBI; the Cowlin Fund (Chicago Community trust); Pfizer; Masimo. | FVC: 57% | Secondary outcomes: changes in the 6MWT distance, degree of dyspnoea, quality of life, FVC, DLCO, arterial partial pressure of oxygen and arterial oxygen saturation, and the alveolar-arterial oxygen gradient while breathing ambient air, adverse events, hospitalisations, death. | |
1. Sildenafil, n = 89 | |||
2. Placebo, n = 91 | |||
Duration of treatment: 12 weeks. | |||
Length of follow-up: 12 weeks | |||
Non-pharmacological interventions | |||
Disease management programme/Pulmonary Rehabilitation | |||
Lindell et al. 2010 [26] | Mean Age: 66 years | Primary outcomes: Not specified as primary or secondary outcomes. Dyspnoea (UCSDSBQ); Anxiety (BAI); Depression (BDI-II); Stress (PSS); QoL (SF-36) | Unclear risk |
Country: USA | M/F%: 76/24 | ||
Design: RCT | Time since diagnosis: NR | ||
Number of centres: one | FVC: >55: 70% | ||
Funding: Fairbanks-Horix Foundation | |||
Interventions: | Length of follow-up: Unclear | ||
1. Program to Reduce IPF Symptoms and Improve Management (PRISIM), n = 10 pairs | |||
2. Usual care, n = 11 pairs | |||
Duration of treatment: 6 weeks | |||
Jastrzebski et al. 2008 [27] | Mean Age: 56 years | Primary outcomes: not specified as primary or secondary. Dyspnoea (oxygen cost diagram, baseline dyspnoea index). QoL (SF-36), 6MWT (distance, dyspnoea in Borg’s scale), maximal inspiratory pressure, lung function tests (IC, TLC, VC, FEV1, DLCOSB, DLCO/VA). | High risk |
Country: Poland | M/F%: 64/36 | ||
Design: CCT | Time since diagnosis: >2 | ||
Number of centres: one | years | ||
Funding: not translated | FVC: 68% | ||
Interventions: | |||
1. Inspiratory muscle training, n = 16 | |||
2. Control, n = 14 | Length of follow-up: 12 weeks | ||
Duration of treatment: 12 weeks (two six week cycles) | |||
Nishiyama et al. 2008 [25] | Mean Age: 66 years | Primary outcomes: not specified as primary or secondary. Pulmonary function tests (FVC, FEV1, TLC, PaO2,PaCO2,) DLCO, 6MWT; BDI; SGRQ | Unclear risk |
Country: Japan | M/F%: 76/24 | ||
Design: RCT | Time since diagnosis: NR | ||
Number of centres: one | FVC: 67% | ||
Funding: Japanese ministry of health, labor and welfare | Length of follow-up: 10 weeks after the start of the programme. | ||
Interventions: | |||
1. Pulmonary rehabilitation programme (PRP), n = 15 (13 analysed) | |||
2. Control, n = 15 | |||
Duration of treatment: 10 week programme. |