Table 2

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

S noTrial number/siteDrug/
Drug dose/
Mechanism of actionTrial design/participantComparator armPrimary end pointPhaseCurrent status
1.NCT04338802/ChinaOral nintedanib150 mg BD × 8 weeksAntifibroticRCT, open label, single centre, 96 subjectsPlaceboChange in FVC after 8 weeks of treatment compared with baselineIIOngoing
2.NCT04282902/ChinaOral pirfenidoneTwo tablets (200 mg each) three times a day
4 weeks or longer
AntifibroticRCT, 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.

3.NCT04288102/ChinaHuman umbilical cord-derived mesenchymal stem cellsIntravenous 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 regenerationRCT, multicentre; 100 subjectsIntravenous 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.

4.NCT04279197/ChinaFuzheng 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)UnclearRCT, double blind multicentre, 160 participantsBasic 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

Pamrevlumab35 mg/kg on days 1, 7, 14 and 28 for a total of four infusions over 4 weeksMonoclonal antibody against connective-tissue growth factor: antifibroticRandomised, double-blind, placebo-controlled ; 130 subjectsPlacebo: 35 mg/kg on days 1, 7, 14 and 28 for a total of four infusions over 4 weeksProportion of subjects who never received mechanical ventilation and/or ECMO and aliveIIOngoing
6.NCT04334460, Brazil and USAB-2660–204Oral 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 subjectsPlacebo
  • Time to recovery.

  • Change in oxygenation.

  • Reduction in viral burden, improvement in cardiopulmonary function and functional recovery.

7.NCT0430831/ChinaTetrandrine (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 protocolSurvival rate in 12 weeks follow-upIVOngoing
(traditional Chinese medicine)
Anluohuaxian +regular treatment group 6 g each time, twice a dayAntifibroticRandomised, open label multicentre; 750 participantsRegular treatment group
  • Changes in HRCT of the lung in 3 months.

  • Change in 6 min walking distance in 3 months.

9.NCT04319731/USAHuman amniotic fluidIntravenous 10 mL purified (acellular) amniotic fluid every 24 hours for 5 days (6 mL)Reduces inflammation and fibrosisSingle group, open label, pilot study; 10 participantsNA
  • Ventilator-free days.

  • Duration of supplemental oxygen use.

Early phase IOngoing
10.Preclinical studyPneumoBlast cell therapyPneumoBlast cell therapy: fibroblast-based cell therapy/dose: NR‘Universal donor’ fibroblasts: produces potent anti-inflammatory protein IL-1 receptor antagonist: prevent scar tissueNRBone 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.

  • 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.