Table 2

Review of preclinical/clinical trials on antifibrotic therapies in COVID-19

S no	Trial number/site	Drug/ therapy	Drug dose/ duration	Mechanism of action	Trial design/participant	Comparator arm	Primary end point	Phase	Current status
1.	NCT04338802/China	Oral nintedanib	150 mg BD × 8 weeks	Antifibrotic	RCT, open label, single centre, 96 subjects	Placebo	Change in FVC after 8 weeks of treatment compared with baseline	II	Ongoing
2.	NCT04282902/China	Oral pirfenidone	Two tablets (200 mg each) three times a day 4 weeks or longer	Antifibrotic	RCT, open label multicentre; 294 participants (147 each arm)	Standard treatment	Improvement in HRCT image at 4 weeks. Absolute change in pulse oxygen from baseline. Absolute change in blood gas from baseline. Absolute change in total score of King’s brief questionnaire for interstitial pulmonary disease from baseline at week 4.	III	Ongoing
3.	NCT04288102/China	Human umbilical cord-derived mesenchymal stem cells	Intravenous three doses of UC-MSCs (4.0*10E7 cells/time) at day 0, day 3, day 6 plus standard of care	Reduces non-productive inflammation and affects tissue regeneration	RCT, multicentre; 100 subjects	Intravenous three doses of placebo (saline containing 1% human serum albumin) at day 0, day 3, day 6 plus standard of care	Change in lesion proportion of full lung volume from baseline to day 28. Secondary endpoint: Pulmonary fibrosis related morphological features in CT scan at day 90. Change in FVC and DLCO.	II	Ongoing
4.	NCT04279197/China	Fuzheng Huayu (traditional Chinese medicine)	1.6 g (0.4 g each tablet) three times a day, plus basic treatment (respiratory function rehabilitation training +vitamin C tablets 0.2 g three times a day)	Unclear	RCT, double blind multicentre, 160 participants	Basic treatment (respiratory function rehabilitation training +vitamin C tablets 0.2 g three times a day) plus placebo	Evaluation of Pulmonary fibrosis Improvement on HRCT Improvement in 6 min walk test distance after 24 weeks	II	Ongoing
5.	NCT04432298 Italy	Pamrevlumab	35 mg/kg on days 1, 7, 14 and 28 for a total of four infusions over 4 weeks	Monoclonal antibody against connective-tissue growth factor: antifibrotic	Randomised, double-blind, placebo-controlled ; 130 subjects	Placebo: 35 mg/kg on days 1, 7, 14 and 28 for a total of four infusions over 4 weeks	Proportion of subjects who never received mechanical ventilation and/or ECMO and alive	II	Ongoing
6.	NCT04334460, Brazil and USA	B-2660–204	Oral B-2660–204 (dose: NA)	Small molecule inhibitor of calpain 1, 2 and 9. Antifibrotic effect: significant reductions in the alpha smooth muscle actin and collagen 1 in lung tissue.	RCT, double blind multicentre, placebo-controlled; 120 subjects	Placebo	Time to recovery. Change in oxygenation. Reduction in viral burden, improvement in cardiopulmonary function and functional recovery.	II	Ongoing
7.	NCT0430831/China	Tetrandrine (traditional Chinese medicine)	Tetrandrine 60 mg once a day × 6 days	Antagonist of calmodulin: anti-inflammatory effects. Inhibit fibroblasts – inhibiting pulmonary fibrosis.	RCT, open label single centre; 60 subjects	Control cohort : standard treatment protocol	Survival rate in 12 weeks follow-up	IV	Ongoing
8.	NCT04334265/China	Anluohuaxian (traditional Chinese medicine)	Anluohuaxian +regular treatment group 6 g each time, twice a day	Antifibrotic	Randomised, open label multicentre; 750 participants	Regular treatment group	Changes in HRCT of the lung in 3 months. Change in 6 min walking distance in 3 months.	NR	Ongoing
9.	NCT04319731/USA	Human amniotic fluid	Intravenous 10 mL purified (acellular) amniotic fluid every 24 hours for 5 days (6 mL)	Reduces inflammation and fibrosis	Single group, open label, pilot study; 10 participants	NA	Ventilator-free days. Duration of supplemental oxygen use.	Early phase I	Ongoing
10.	Preclinical study	PneumoBlast cell therapy	PneumoBlast cell therapy: fibroblast-based cell therapy/dose: NR	‘Universal donor’ fibroblasts: produces potent anti-inflammatory protein IL-1 receptor antagonist: prevent scar tissue	NR	Bone marrow derived mesenchymal stem cells	Reduced lung fibrosis by 51% in a bleomycin model of lung scarring in mice. PneumoBlast : 221% more effective than bone marrow derived mesenchymal stem cells.	Preclinical	Completed

DLCO, diffusing capacity for carbon monoxide; FVC, forced vital capacity; HRCT, high resolution CT; IL-1, interleukin 1; NA, not available; NR, not reported; RCT, Randomised controlled trial.