Table 2.

Major phase 3 clinical trials on serelaxin

Clinical trial (Acronym)	Clinical trials. Gov identifier	Participants	CV condition	Intervention	Study duration	Main results
Serelaxin, recombinant human relaxin-2, for treatment of acute heart failure: a randomized, placebo-controlled trial (RELAX-AHF) [24]	NCT00520806	1161 participants Follow-up: 180 days Time to randomization ± SD (hours): 7.9 ± 4.63 Mean age ± SD (years) Treatment group: 71.6 ± 11.7 Control group: 72.5 ± 10.8	AHF	Treatment group Serelaxin:30 μg/kg/day Control group Placebo	October 2009 to September 2012	- Significant improvement in dyspnea measured by VAS AUC (P = 0.007) - No significant improvement in patient-reported dyspnea (P = 0.70) - Significant reduction of WHF up to day 14 (P = 0.024) - Significant reduction of all-cause mortality (P = 0.019) and CV death (P = 0.028) at day 180 - Significant reduction of LoS by 0.9 days (P = 0.04) - No significant reduction of CV death or readmissions to day 60 (P = 0.89) - Significant decrease in AEs related to renal impairment (P = 0.03)
A multicenter, randomised, double-blind, placebo-controlled phase III study to evaluate the efficacy, safety and tolerability of serelaxin when added to standard therapy in acute heart failure patients (RELAX-AHF-2) [27]	NCT01870778	6545 participants Follow-up: 180 days Time to randomization ± SD (hours): 8.13 ± 4.49 Mean age ± SD (years): Treatment group: 73.1 ± 11.2 Control group: 72.8 ± 11.2	AHF	Treatment group Serelaxin 30 μg/kg/day Control group Placebo	June 2013 to February 2017	- No significant reduction of CV death at day 180 (P = 0.77) - No significant reduction of WHF at day 5 (P = 0.19) - Similar all-cause death and CV death or readmission 180 at days - Similar LoS - Similar number of AEs and SAEs
Efficacy, Safety and Tolerability of Sexelaxin When Added to Standard Therapy in AHF (RELAX-AHF- ASIA) [29, 32]	NCT02007720	876 participants Follow-up: 180 days Mean age ± SD (years): Treatment group: 68.9 ± 14.40 Control group: 70.2 ± 13.86	AHF	Treatment group Serelaxin 30 μg/kg/day Control group Placebo	December 2013 to June 2017	- No significant reduction in patients with treatment failure in the serelaxin group (4.1%) vs placebo group (8.3%) - Significant reduction of WHF at day 5 (HR = of 0.41, P = 0.0119) - No significant reduction in CV death and all-cause mortality at day 180 - Similar frequency of SAEs
Efficacy and safety of serelaxin when added to standard of care in patients with acute heart failure: results from a PROBE study (RELAX-AHF- EU)[33]	NCT02064868	2650 participants Follow-up: 30 days Mean age ± SD (years): Treatment group: 75.24 ± 10.349 Control group: 75.95 ± 9.905	AHF	Treatment group SoC + Serelaxin 30 μg/kg/day Control group SoC	February 2014 to April 2017	- Significant reduction of adjudicated WHF and all-cause of death through Day 5 (HR = 0.71 [95% CI 0.51–0.98] P = 0.0172) - No significant reduction of investigator-reported WHF or all-cause of death through day 5 (HR = 0.78 [95% CI 0.59–1.0] P = 0.029) - Significant reduction in persistent HF signs/symptoms up to day 4 (all P ≤ 0.01) - No significant reduction in WHF, all-cause death or HF readmissions through day 14 (P = 0.0634) - No significant change in LoS - Significant reduction in renal deterioration through day 5 and at discharge (all P ≤ 0.01) - AEs profile was similar

It includes the information on target disease, patient population, intervention dosage and key findings

CI confidence interval, SD standard deviation, HR hazard ratio, CV cardiovascular, VAS visual analogue scale, AUC area under the curve, AHF acute heart failure, HF heart failure, LoS length of stay, WHF worsening heart failure, SoC standard of care, AEs adverse events, SAEs serious adverse event