Trial Outcomes & Findings for IV Iron Replacement for Iron Deficiency in Idiopathic Pulmonary Arterial Hypertension (IPAH) Patients (NCT NCT01447628)

NCT ID: NCT01447628

Last Updated: 2022-03-07

Results Overview

Time measured in seconds from start to end of the endurance bicycle cardiopulmonary exercise testing at 80% of the peak work rate. Peak work rate is determined by that achieved at the baseline incremental cardiopulmonary exercise test (CPET). Note that this was the primary end-point of the European study. Endurance CPET was not done in China.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 56 participants
• Primary outcome timeframe: 12 Weeks post study treatment
• Results posted on: 2022-03-07

Participant Flow

The groups are separated into Europe and China, because a different Investigational Medicinal Product (IMP) was used and outcome measures were analysed separately.

Participant milestones

Measure	Ferinject Followed by Placebo (Europe) IV iron formulation used in Europe - Ferinject (Intravenous, 1000 mg iron)- given over 15 minutes followed by Placebo given as 1000mg saline according to randomisation. Ferinject administered at week 0, placebo (saline) administered at week 12.	Placebo Followed by Ferinject (Europe) IV iron formulation used in Europe - Ferinject (Intravenous, 1000 mg iron)- given over 15 minutes or Placebo given as 1000mg saline according to randomisation. Placebo (saline) administered at week 0, Ferinject administered at week 12.	Cosmofer Followed by Placebo (China) IV iron formulation used in China was CosmoFer - given intravenously over a period of 4 to 6 hours Cosmofer administered at week 0, placebo (saline) administered at week 12.	Placebo Followed by Cosmofer (China) IV iron formulation used in China was CosmoFer - given intravenously over a period of 4 to 6 hours Placebo (saline) administered at week 0, Cosmofer administered at week 12.
Week 0 to Week 12 (1st Intervention) STARTED	19	20	12	5
Week 0 to Week 12 (1st Intervention) COMPLETED	19	20	12	4
Week 0 to Week 12 (1st Intervention) NOT COMPLETED	0	0	0	1
Week 12 to Week 24 (2nd Intervention) STARTED	19	20	12	4
Week 12 to Week 24 (2nd Intervention) COMPLETED	19	20	12	4
Week 12 to Week 24 (2nd Intervention) NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Measure	Ferinject Followed by Placebo (Europe) IV iron formulation used in Europe - Ferinject (Intravenous, 1000 mg iron)- given over 15 minutes followed by Placebo given as 1000mg saline according to randomisation. Ferinject administered at week 0, placebo (saline) administered at week 12.	Placebo Followed by Ferinject (Europe) IV iron formulation used in Europe - Ferinject (Intravenous, 1000 mg iron)- given over 15 minutes or Placebo given as 1000mg saline according to randomisation. Placebo (saline) administered at week 0, Ferinject administered at week 12.	Cosmofer Followed by Placebo (China) IV iron formulation used in China was CosmoFer - given intravenously over a period of 4 to 6 hours Cosmofer administered at week 0, placebo (saline) administered at week 12.	Placebo Followed by Cosmofer (China) IV iron formulation used in China was CosmoFer - given intravenously over a period of 4 to 6 hours Placebo (saline) administered at week 0, Cosmofer administered at week 12.
Week 0 to Week 12 (1st Intervention) Adverse Event	0	0	0	1

Baseline Characteristics

IV Iron Replacement for Iron Deficiency in Idiopathic Pulmonary Arterial Hypertension (IPAH) Patients

Baseline characteristics by cohort

Measure	European Dataset n=39 Participants IV iron (1000 mg) formulation used in Europe - Ferinject - given over 15 minutes Saline: intravenous, no active drug	China Dataset n=17 Participants IV iron (1000mg) formulation used in China - CosmoFer - over a period of 4 to 6 hours Saline: intravenous, no active drug	Total n=56 Participants Total of all reporting groups
Age, Continuous	49.4 years n=5 Participants	32.58 years n=7 Participants	44.3 years n=5 Participants
Sex: Female, Male Female	29 Participants n=5 Participants	15 Participants n=7 Participants	44 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	2 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	17 Participants n=7 Participants	20 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	36 Participants n=5 Participants	0 Participants n=7 Participants	36 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment China	0 participants n=5 Participants	17 participants n=7 Participants	17 participants n=5 Participants
Region of Enrollment United Kingdom	34 participants n=5 Participants	0 participants n=7 Participants	34 participants n=5 Participants
Region of Enrollment Germany	5 participants n=5 Participants	0 participants n=7 Participants	5 participants n=5 Participants

PRIMARY outcome

Timeframe: 12 Weeks post study treatment

Population: Intention to treat (ITT)

Time measured in seconds from start to end of the endurance bicycle cardiopulmonary exercise testing at 80% of the peak work rate. Peak work rate is determined by that achieved at the baseline incremental cardiopulmonary exercise test (CPET).

Note that this was the primary end-point of the European study. Endurance CPET was not done in China.

Outcome measures

Measure	Cosmofer Group (China) This group provides the outcome measurements for participants following their infusion of CosmoFer, whether this was at the first or second timepoint. IV iron formulation used in China was CosmoFer - given intravenously over a period of 4 to 6 hours	Placebo Group (China) This group provides the outcome measurements for participants from the Fuwai site following their infusion of Placebo (saline, infused over 4-6hrs), whether this was at the first or second timepoint.	Ferinject Group (Europe) n=39 Participants IV iron formulation used in Europe - Ferinject (Intravenous, 1000 mg iron)- given over 15 minutes This group provides the outcome measurements for participants following their infusion of Ferinject, whether this was at the first or second timepoint	Placebo Group (Europe) n=39 Participants Placebo (saline) given intravenously over 15 minutes. This group provides the outcome measurements for participants following their infusion of Placebo, whether this was at the first or second timepoint
Change in Exercise Capacity - Endurance	—	—	315.44 Seconds Interval 274.68 to 356.2	302.89 Seconds Interval 260.09 to 345.69

PRIMARY outcome

Timeframe: 12 weeks post study treatment

To be measured by cardiac catheterisation in wood units.

Outcome measures

Measure	Cosmofer Group (China) n=17 Participants This group provides the outcome measurements for participants following their infusion of CosmoFer, whether this was at the first or second timepoint. IV iron formulation used in China was CosmoFer - given intravenously over a period of 4 to 6 hours	Placebo Group (China) n=17 Participants This group provides the outcome measurements for participants from the Fuwai site following their infusion of Placebo (saline, infused over 4-6hrs), whether this was at the first or second timepoint.	Ferinject Group (Europe) n=39 Participants IV iron formulation used in Europe - Ferinject (Intravenous, 1000 mg iron)- given over 15 minutes This group provides the outcome measurements for participants following their infusion of Ferinject, whether this was at the first or second timepoint	Placebo Group (Europe) n=39 Participants Placebo (saline) given intravenously over 15 minutes. This group provides the outcome measurements for participants following their infusion of Placebo, whether this was at the first or second timepoint
Change in Resting Pulmonary Vascular Resistance (PVR)	11.70 Wood units Interval 9.16 to 14.04	9.5 Wood units Interval 6.25 to 13.81	7.69 Wood units Interval 5.71 to 9.17	5.15 Wood units Interval 3.61 to 7.27

SECONDARY outcome

Timeframe: 12 weeks post study treatment

Level of VO2 at peak measured during incremental cardio-pulmonary exercise testing

Outcome measures

Measure	Cosmofer Group (China) n=17 Participants This group provides the outcome measurements for participants following their infusion of CosmoFer, whether this was at the first or second timepoint. IV iron formulation used in China was CosmoFer - given intravenously over a period of 4 to 6 hours	Placebo Group (China) n=17 Participants This group provides the outcome measurements for participants from the Fuwai site following their infusion of Placebo (saline, infused over 4-6hrs), whether this was at the first or second timepoint.	Ferinject Group (Europe) n=39 Participants IV iron formulation used in Europe - Ferinject (Intravenous, 1000 mg iron)- given over 15 minutes This group provides the outcome measurements for participants following their infusion of Ferinject, whether this was at the first or second timepoint	Placebo Group (Europe) n=39 Participants Placebo (saline) given intravenously over 15 minutes. This group provides the outcome measurements for participants following their infusion of Placebo, whether this was at the first or second timepoint
Oxygen Consumption (VO2) Level at Peak 12 Weeks After Study Treatment	0.93 Litres per minute Interval 0.87 to 1.0	0.94 Litres per minute Interval 0.84 to 0.97	1.17 Litres per minute Interval 1.1 to 1.22	1.13 Litres per minute Interval 1.08 to 1.21

SECONDARY outcome

Timeframe: 12 weeks post study treatment

Level of VO2 at metabolic threshold measured during incremental cardio-pulmonary exercise test

Outcome measures

Measure	Cosmofer Group (China) n=17 Participants This group provides the outcome measurements for participants following their infusion of CosmoFer, whether this was at the first or second timepoint. IV iron formulation used in China was CosmoFer - given intravenously over a period of 4 to 6 hours	Placebo Group (China) n=17 Participants This group provides the outcome measurements for participants from the Fuwai site following their infusion of Placebo (saline, infused over 4-6hrs), whether this was at the first or second timepoint.	Ferinject Group (Europe) n=39 Participants IV iron formulation used in Europe - Ferinject (Intravenous, 1000 mg iron)- given over 15 minutes This group provides the outcome measurements for participants following their infusion of Ferinject, whether this was at the first or second timepoint	Placebo Group (Europe) n=39 Participants Placebo (saline) given intravenously over 15 minutes. This group provides the outcome measurements for participants following their infusion of Placebo, whether this was at the first or second timepoint
Oxygen Consumption (VO2) at Metabolic Threshold	0.66 Litres per minute Interval 0.58 to 0.76	0.69 Litres per minute Interval 0.59 to 0.77	0.78 Litres per minute Interval 0.73 to 0.82	0.77 Litres per minute Interval 0.73 to 0.82

SECONDARY outcome

Timeframe: 12 weeks post study treatment

VE/VCO2 slope measured during incremental cardio-pulmonary exercise testing

Outcome measures

Measure	Cosmofer Group (China) n=17 Participants This group provides the outcome measurements for participants following their infusion of CosmoFer, whether this was at the first or second timepoint. IV iron formulation used in China was CosmoFer - given intravenously over a period of 4 to 6 hours	Placebo Group (China) n=17 Participants This group provides the outcome measurements for participants from the Fuwai site following their infusion of Placebo (saline, infused over 4-6hrs), whether this was at the first or second timepoint.	Ferinject Group (Europe) n=39 Participants IV iron formulation used in Europe - Ferinject (Intravenous, 1000 mg iron)- given over 15 minutes This group provides the outcome measurements for participants following their infusion of Ferinject, whether this was at the first or second timepoint	Placebo Group (Europe) n=39 Participants Placebo (saline) given intravenously over 15 minutes. This group provides the outcome measurements for participants following their infusion of Placebo, whether this was at the first or second timepoint
Ventilation / Volume of Exhaled Carbon Dioxide (VE/VCO2 Slope)	35.06 l/min/l/min Interval 30.66 to 39.31	36.27 l/min/l/min Interval 31.21 to 39.78	41.15 l/min/l/min Interval 39.43 to 42.93	42.35 l/min/l/min Interval 40.58 to 44.07

SECONDARY outcome

Timeframe: 12 weeks post study treatment

Level of VO2 / WR Slope measured during incremental cardio-pulmonary exercise testing

Outcome measures

Measure	Cosmofer Group (China) n=17 Participants This group provides the outcome measurements for participants following their infusion of CosmoFer, whether this was at the first or second timepoint. IV iron formulation used in China was CosmoFer - given intravenously over a period of 4 to 6 hours	Placebo Group (China) n=17 Participants This group provides the outcome measurements for participants from the Fuwai site following their infusion of Placebo (saline, infused over 4-6hrs), whether this was at the first or second timepoint.	Ferinject Group (Europe) n=39 Participants IV iron formulation used in Europe - Ferinject (Intravenous, 1000 mg iron)- given over 15 minutes This group provides the outcome measurements for participants following their infusion of Ferinject, whether this was at the first or second timepoint	Placebo Group (Europe) n=39 Participants Placebo (saline) given intravenously over 15 minutes. This group provides the outcome measurements for participants following their infusion of Placebo, whether this was at the first or second timepoint
Oxygen Consumption (VO2) / Work Rate (WR) Slope	5.97 ml/min/watt Interval 5.15 to 6.77	6.04 ml/min/watt Interval 5.15 to 6.77	8.12 ml/min/watt Interval 7.5 to 8.71	8.04 ml/min/watt Interval 7.46 to 8.68

SECONDARY outcome

Timeframe: 12 weeks post study treatment

O2 pulse rate (amount of oxygen consumed per heart beat) at peak measured during incremental cardio-pulmonary exercise test

Outcome measures

Measure	Cosmofer Group (China) n=17 Participants This group provides the outcome measurements for participants following their infusion of CosmoFer, whether this was at the first or second timepoint. IV iron formulation used in China was CosmoFer - given intravenously over a period of 4 to 6 hours	Placebo Group (China) n=17 Participants This group provides the outcome measurements for participants from the Fuwai site following their infusion of Placebo (saline, infused over 4-6hrs), whether this was at the first or second timepoint.	Ferinject Group (Europe) n=39 Participants IV iron formulation used in Europe - Ferinject (Intravenous, 1000 mg iron)- given over 15 minutes This group provides the outcome measurements for participants following their infusion of Ferinject, whether this was at the first or second timepoint	Placebo Group (Europe) n=39 Participants Placebo (saline) given intravenously over 15 minutes. This group provides the outcome measurements for participants following their infusion of Placebo, whether this was at the first or second timepoint
Peak Oxygen (O2) Pulse Rate	6.55 ml/beat Interval 6.02 to 7.01	6.36 ml/beat Interval 5.79 to 6.79	13.30 ml/beat Interval 10.0 to 16.59	11.92 ml/beat Interval 8.3 to 15.54

SECONDARY outcome

Timeframe: 12 weeks post study treatment

Level of VO2 measured at end of endurance cardio-pulmonary exercise test. Note that endurance CPET was not done in China, so this is reported only for the European dataset.

Outcome measures

Measure	Cosmofer Group (China) This group provides the outcome measurements for participants following their infusion of CosmoFer, whether this was at the first or second timepoint. IV iron formulation used in China was CosmoFer - given intravenously over a period of 4 to 6 hours	Placebo Group (China) This group provides the outcome measurements for participants from the Fuwai site following their infusion of Placebo (saline, infused over 4-6hrs), whether this was at the first or second timepoint.	Ferinject Group (Europe) n=39 Participants IV iron formulation used in Europe - Ferinject (Intravenous, 1000 mg iron)- given over 15 minutes This group provides the outcome measurements for participants following their infusion of Ferinject, whether this was at the first or second timepoint	Placebo Group (Europe) n=39 Participants Placebo (saline) given intravenously over 15 minutes. This group provides the outcome measurements for participants following their infusion of Placebo, whether this was at the first or second timepoint
Oxygen Consumption (VO2) at the End of Endurance Cardio-pulmonary Exercise Test (CPET)	—	—	4.25 Litres per minute Interval 3.5 to 5.01	4.49 Litres per minute Interval 3.71 to 5.28

SECONDARY outcome

Timeframe: 12 weeks post study treatment

Level of VO2 measured at 3 minutes into endurance cardio-pulmonary exercise test (CPET) Note that endurance CPET was not done in China, hence results are presented only for the European dataset.

Outcome measures

Measure	Cosmofer Group (China) This group provides the outcome measurements for participants following their infusion of CosmoFer, whether this was at the first or second timepoint. IV iron formulation used in China was CosmoFer - given intravenously over a period of 4 to 6 hours	Placebo Group (China) This group provides the outcome measurements for participants from the Fuwai site following their infusion of Placebo (saline, infused over 4-6hrs), whether this was at the first or second timepoint.	Ferinject Group (Europe) n=39 Participants IV iron formulation used in Europe - Ferinject (Intravenous, 1000 mg iron)- given over 15 minutes This group provides the outcome measurements for participants following their infusion of Ferinject, whether this was at the first or second timepoint	Placebo Group (Europe) n=39 Participants Placebo (saline) given intravenously over 15 minutes. This group provides the outcome measurements for participants following their infusion of Placebo, whether this was at the first or second timepoint
Oxygen Consumption (VO2) at 3 Minutes	—	—	1.29 Litres per minute Interval 0.98 to 1.6	1.14 Litres per minute Interval 0.81 to 1.48

SECONDARY outcome

Timeframe: 12 weeks post study treatment

Measurement of serum iron

Outcome measures

Measure	Cosmofer Group (China) n=17 Participants This group provides the outcome measurements for participants following their infusion of CosmoFer, whether this was at the first or second timepoint. IV iron formulation used in China was CosmoFer - given intravenously over a period of 4 to 6 hours	Placebo Group (China) n=17 Participants This group provides the outcome measurements for participants from the Fuwai site following their infusion of Placebo (saline, infused over 4-6hrs), whether this was at the first or second timepoint.	Ferinject Group (Europe) n=39 Participants IV iron formulation used in Europe - Ferinject (Intravenous, 1000 mg iron)- given over 15 minutes This group provides the outcome measurements for participants following their infusion of Ferinject, whether this was at the first or second timepoint	Placebo Group (Europe) n=39 Participants Placebo (saline) given intravenously over 15 minutes. This group provides the outcome measurements for participants following their infusion of Placebo, whether this was at the first or second timepoint
Iron Indices: Serum Iron	15.81 umol/L Interval 12.29 to 19.25	14.31 umol/L Interval 9.83 to 16.79	17.15 umol/L Interval 15.42 to 18.64	15.48 umol/L Interval 13.94 to 17.17

SECONDARY outcome

Timeframe: 12 weeks post study treatment

Measurement of serum transferrin saturations. The saturation measures the iron concentration as a proportion of the iron binding capacity of transferrin.

Outcome measures

Measure	Cosmofer Group (China) n=17 Participants This group provides the outcome measurements for participants following their infusion of CosmoFer, whether this was at the first or second timepoint. IV iron formulation used in China was CosmoFer - given intravenously over a period of 4 to 6 hours	Placebo Group (China) n=17 Participants This group provides the outcome measurements for participants from the Fuwai site following their infusion of Placebo (saline, infused over 4-6hrs), whether this was at the first or second timepoint.	Ferinject Group (Europe) n=39 Participants IV iron formulation used in Europe - Ferinject (Intravenous, 1000 mg iron)- given over 15 minutes This group provides the outcome measurements for participants following their infusion of Ferinject, whether this was at the first or second timepoint	Placebo Group (Europe) n=39 Participants Placebo (saline) given intravenously over 15 minutes. This group provides the outcome measurements for participants following their infusion of Placebo, whether this was at the first or second timepoint
Iron Indices: Transferrin Saturations	26.81 percentage of iron occupied transferrin Interval 20.81 to 31.51	22.88 percentage of iron occupied transferrin Interval 15.27 to 26.0	26.2 percentage of iron occupied transferrin Interval 22.96 to 28.89	22 percentage of iron occupied transferrin Interval 19.21 to 25.12

SECONDARY outcome

Timeframe: 12 weeks post study treatment

Measured level of serum ferritin

Outcome measures

Measure	Cosmofer Group (China) n=17 Participants This group provides the outcome measurements for participants following their infusion of CosmoFer, whether this was at the first or second timepoint. IV iron formulation used in China was CosmoFer - given intravenously over a period of 4 to 6 hours	Placebo Group (China) n=17 Participants This group provides the outcome measurements for participants from the Fuwai site following their infusion of Placebo (saline, infused over 4-6hrs), whether this was at the first or second timepoint.	Ferinject Group (Europe) n=39 Participants IV iron formulation used in Europe - Ferinject (Intravenous, 1000 mg iron)- given over 15 minutes This group provides the outcome measurements for participants following their infusion of Ferinject, whether this was at the first or second timepoint	Placebo Group (Europe) n=39 Participants Placebo (saline) given intravenously over 15 minutes. This group provides the outcome measurements for participants following their infusion of Placebo, whether this was at the first or second timepoint
Iron Indices: Ferritin	135.06 ug/L Interval 122.79 to 165.29	65.5 ug/L Interval 44.27 to 86.77	150.32 ug/L Interval 118.63 to 175.51	92.74 ug/L Interval 66.08 to 122.88

SECONDARY outcome

Timeframe: 12 weeks post study treatment

Measure of serum sTfR level. Note that this was not measured in China, hence is reported only for the European dataset.

Outcome measures

Measure	Cosmofer Group (China) This group provides the outcome measurements for participants following their infusion of CosmoFer, whether this was at the first or second timepoint. IV iron formulation used in China was CosmoFer - given intravenously over a period of 4 to 6 hours	Placebo Group (China) This group provides the outcome measurements for participants from the Fuwai site following their infusion of Placebo (saline, infused over 4-6hrs), whether this was at the first or second timepoint.	Ferinject Group (Europe) n=39 Participants IV iron formulation used in Europe - Ferinject (Intravenous, 1000 mg iron)- given over 15 minutes This group provides the outcome measurements for participants following their infusion of Ferinject, whether this was at the first or second timepoint	Placebo Group (Europe) n=39 Participants Placebo (saline) given intravenously over 15 minutes. This group provides the outcome measurements for participants following their infusion of Placebo, whether this was at the first or second timepoint
Iron Indices: Soluble Transferrin Receptors (sTfR)	—	—	28.37 nmol/L Interval 25.73 to 31.72	37.25 nmol/L Interval 34.02 to 40.0

SECONDARY outcome

Timeframe: 12 weeks post study treatment

Distance in metres walked during standardised and validated 6 minute walk test

Outcome measures

Measure	Cosmofer Group (China) n=17 Participants This group provides the outcome measurements for participants following their infusion of CosmoFer, whether this was at the first or second timepoint. IV iron formulation used in China was CosmoFer - given intravenously over a period of 4 to 6 hours	Placebo Group (China) n=17 Participants This group provides the outcome measurements for participants from the Fuwai site following their infusion of Placebo (saline, infused over 4-6hrs), whether this was at the first or second timepoint.	Ferinject Group (Europe) n=39 Participants IV iron formulation used in Europe - Ferinject (Intravenous, 1000 mg iron)- given over 15 minutes This group provides the outcome measurements for participants following their infusion of Ferinject, whether this was at the first or second timepoint	Placebo Group (Europe) n=39 Participants Placebo (saline) given intravenously over 15 minutes. This group provides the outcome measurements for participants following their infusion of Placebo, whether this was at the first or second timepoint
6 Minute Walk Test: Distance Walked	478 Metres Interval 448.96 to 523.59	474.19 Metres Interval 443.73 to 518.37	426.03 Metres Interval 411.57 to 440.2	424.3 Metres Interval 410.06 to 438.7

SECONDARY outcome

Timeframe: 12 weeks post study treatment

Participant reported score on the modified Borg Dyspnoea scale (0-10) following 6 minute walk test. Higher scores indicate worsened dyspnoea.

Outcome measures

Measure	Cosmofer Group (China) n=17 Participants This group provides the outcome measurements for participants following their infusion of CosmoFer, whether this was at the first or second timepoint. IV iron formulation used in China was CosmoFer - given intravenously over a period of 4 to 6 hours	Placebo Group (China) n=17 Participants This group provides the outcome measurements for participants from the Fuwai site following their infusion of Placebo (saline, infused over 4-6hrs), whether this was at the first or second timepoint.	Ferinject Group (Europe) n=39 Participants IV iron formulation used in Europe - Ferinject (Intravenous, 1000 mg iron)- given over 15 minutes This group provides the outcome measurements for participants following their infusion of Ferinject, whether this was at the first or second timepoint	Placebo Group (Europe) n=39 Participants Placebo (saline) given intravenously over 15 minutes. This group provides the outcome measurements for participants following their infusion of Placebo, whether this was at the first or second timepoint
6 Minute Walk Test: Borg Dyspnoea Score After Test	1.38 units on a scale Interval 0.72 to 2.0	1.28 units on a scale Interval 0.66 to 1.93	3.24 units on a scale Interval 2.75 to 3.75	3.68 units on a scale Interval 3.18 to 4.17

SECONDARY outcome

Timeframe: 12 weeks post study treatment

Measured level of NT-pro-BNP in blood sample. Note that this was not measured in China, hence is presented only for the European dataset.

Outcome measures

Measure	Cosmofer Group (China) This group provides the outcome measurements for participants following their infusion of CosmoFer, whether this was at the first or second timepoint. IV iron formulation used in China was CosmoFer - given intravenously over a period of 4 to 6 hours	Placebo Group (China) This group provides the outcome measurements for participants from the Fuwai site following their infusion of Placebo (saline, infused over 4-6hrs), whether this was at the first or second timepoint.	Ferinject Group (Europe) n=39 Participants IV iron formulation used in Europe - Ferinject (Intravenous, 1000 mg iron)- given over 15 minutes This group provides the outcome measurements for participants following their infusion of Ferinject, whether this was at the first or second timepoint	Placebo Group (Europe) n=39 Participants Placebo (saline) given intravenously over 15 minutes. This group provides the outcome measurements for participants following their infusion of Placebo, whether this was at the first or second timepoint
Iron Indices: N-terminal Pro B-type Natriuretic Peptide (NT-pro-BNP)	—	—	307.64 fmol/ml Interval 186.47 to 437.62	394.94 fmol/ml Interval 297.52 to 548.39

SECONDARY outcome

Timeframe: 12 weeks post study treatment

Participant self reported symptom score using the CAMPHOR questionnaire (0-25). Scores for symptoms range from 0-25, with higher scores indicating worse symptoms.

Note that this was not measured in China, hence is presented only for the European dataset.

Outcome measures

Measure	Cosmofer Group (China) This group provides the outcome measurements for participants following their infusion of CosmoFer, whether this was at the first or second timepoint. IV iron formulation used in China was CosmoFer - given intravenously over a period of 4 to 6 hours	Placebo Group (China) This group provides the outcome measurements for participants from the Fuwai site following their infusion of Placebo (saline, infused over 4-6hrs), whether this was at the first or second timepoint.	Ferinject Group (Europe) n=39 Participants IV iron formulation used in Europe - Ferinject (Intravenous, 1000 mg iron)- given over 15 minutes This group provides the outcome measurements for participants following their infusion of Ferinject, whether this was at the first or second timepoint	Placebo Group (Europe) n=39 Participants Placebo (saline) given intravenously over 15 minutes. This group provides the outcome measurements for participants following their infusion of Placebo, whether this was at the first or second timepoint
Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR Questionnaire): Symptom Score	—	—	7.94 score on a scale Interval 6.99 to 8.89	7.94 score on a scale Interval 7.02 to 8.89

SECONDARY outcome

Timeframe: 12 weeks post study treatment

Participants' self reported score of their own level of activity based on the CAMPHOR questionnaire.

Activity scores range from 0-30, with higher scores indicating more physical limitations Note that this was not measured in China, hence is presented only for the European dataset.

Outcome measures

Measure	Cosmofer Group (China) This group provides the outcome measurements for participants following their infusion of CosmoFer, whether this was at the first or second timepoint. IV iron formulation used in China was CosmoFer - given intravenously over a period of 4 to 6 hours	Placebo Group (China) This group provides the outcome measurements for participants from the Fuwai site following their infusion of Placebo (saline, infused over 4-6hrs), whether this was at the first or second timepoint.	Ferinject Group (Europe) n=39 Participants IV iron formulation used in Europe - Ferinject (Intravenous, 1000 mg iron)- given over 15 minutes This group provides the outcome measurements for participants following their infusion of Ferinject, whether this was at the first or second timepoint	Placebo Group (Europe) n=39 Participants Placebo (saline) given intravenously over 15 minutes. This group provides the outcome measurements for participants following their infusion of Placebo, whether this was at the first or second timepoint
Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR Questionnaire): Activity Score	—	—	9.12 units on a scale Interval 8.14 to 10.07	9.18 units on a scale Interval 8.25 to 10.16

SECONDARY outcome

Timeframe: 12 weeks post study treatment

Quality of Life score based on the Cambridge Pulmonary Hypertension Outcomes Review (CAMPHOR) questionnaire (0-25).

Scores for QoL range from 0-25, with higher scores indicating worse quality of life Note that this was not measured in China, hence is presented only for the European dataset.

Outcome measures

Measure	Cosmofer Group (China) This group provides the outcome measurements for participants following their infusion of CosmoFer, whether this was at the first or second timepoint. IV iron formulation used in China was CosmoFer - given intravenously over a period of 4 to 6 hours	Placebo Group (China) This group provides the outcome measurements for participants from the Fuwai site following their infusion of Placebo (saline, infused over 4-6hrs), whether this was at the first or second timepoint.	Ferinject Group (Europe) n=39 Participants IV iron formulation used in Europe - Ferinject (Intravenous, 1000 mg iron)- given over 15 minutes This group provides the outcome measurements for participants following their infusion of Ferinject, whether this was at the first or second timepoint	Placebo Group (Europe) n=39 Participants Placebo (saline) given intravenously over 15 minutes. This group provides the outcome measurements for participants following their infusion of Placebo, whether this was at the first or second timepoint
Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR Questionnaire): QoL Score	—	—	7.58 units on a scale Interval 6.38 to 8.69	7 units on a scale Interval 5.91 to 8.16

SECONDARY outcome

Timeframe: 12 weeks post study treatment

Mean right atrial pressure at rest measured by cardiac catheter

Outcome measures

Measure	Cosmofer Group (China) n=17 Participants This group provides the outcome measurements for participants following their infusion of CosmoFer, whether this was at the first or second timepoint. IV iron formulation used in China was CosmoFer - given intravenously over a period of 4 to 6 hours	Placebo Group (China) n=17 Participants This group provides the outcome measurements for participants from the Fuwai site following their infusion of Placebo (saline, infused over 4-6hrs), whether this was at the first or second timepoint.	Ferinject Group (Europe) n=39 Participants IV iron formulation used in Europe - Ferinject (Intravenous, 1000 mg iron)- given over 15 minutes This group provides the outcome measurements for participants following their infusion of Ferinject, whether this was at the first or second timepoint	Placebo Group (Europe) n=39 Participants Placebo (saline) given intravenously over 15 minutes. This group provides the outcome measurements for participants following their infusion of Placebo, whether this was at the first or second timepoint
Mean Right Atrial Pressure (Cardiac Catheter)	6.67 mmHg Interval 4.55 to 7.91	4.5 mmHg Interval 3.21 to 8.48	6.56 mmHg Interval 5.4 to 9.23	10.12 mmHg Interval 7.17 to 11.21

SECONDARY outcome

Timeframe: 12 weeks post study treatment

VO2 at peak of Incremental Cardio-pulmonary exercise test in ml/min/kg

Outcome measures

Measure	Cosmofer Group (China) n=17 Participants This group provides the outcome measurements for participants following their infusion of CosmoFer, whether this was at the first or second timepoint. IV iron formulation used in China was CosmoFer - given intravenously over a period of 4 to 6 hours	Placebo Group (China) n=17 Participants This group provides the outcome measurements for participants from the Fuwai site following their infusion of Placebo (saline, infused over 4-6hrs), whether this was at the first or second timepoint.	Ferinject Group (Europe) n=39 Participants IV iron formulation used in Europe - Ferinject (Intravenous, 1000 mg iron)- given over 15 minutes This group provides the outcome measurements for participants following their infusion of Ferinject, whether this was at the first or second timepoint	Placebo Group (Europe) n=39 Participants Placebo (saline) given intravenously over 15 minutes. This group provides the outcome measurements for participants following their infusion of Placebo, whether this was at the first or second timepoint
Oxygen Consumption (VO2) Level at Peak	14.53 ml/min/kg Interval 12.83 to 16.68	14.36 ml/min/kg Interval 11.21 to 15.09	15.10 ml/min/kg Interval 14.1 to 15.58	14.67 ml/min/kg Interval 14.2 to 15.68

SECONDARY outcome

Timeframe: 12 weeks post treatment

VO2 at Metabolic Threshold measured during incremental cardio-pulmonary exercise test

Outcome measures

Measure	Cosmofer Group (China) n=17 Participants This group provides the outcome measurements for participants following their infusion of CosmoFer, whether this was at the first or second timepoint. IV iron formulation used in China was CosmoFer - given intravenously over a period of 4 to 6 hours	Placebo Group (China) n=17 Participants This group provides the outcome measurements for participants from the Fuwai site following their infusion of Placebo (saline, infused over 4-6hrs), whether this was at the first or second timepoint.	Ferinject Group (Europe) n=39 Participants IV iron formulation used in Europe - Ferinject (Intravenous, 1000 mg iron)- given over 15 minutes This group provides the outcome measurements for participants following their infusion of Ferinject, whether this was at the first or second timepoint	Placebo Group (Europe) n=39 Participants Placebo (saline) given intravenously over 15 minutes. This group provides the outcome measurements for participants following their infusion of Placebo, whether this was at the first or second timepoint
Oxygen Consumption (VO2) at Metabolic Threshold	10.91 ml/min/kg Interval 9.98 to 12.06	11.2 ml/min/kg Interval 9.77 to 11.86	10.01 ml/min/kg Interval 9.45 to 10.46	9.99 ml/min/kg Interval 9.52 to 10.53

SECONDARY outcome

Timeframe: 12 weeks post treatment

Measurement of stroke volume at rest by cardiac catheter at 12 weeks post treatment

Outcome measures

Measure	Cosmofer Group (China) n=17 Participants This group provides the outcome measurements for participants following their infusion of CosmoFer, whether this was at the first or second timepoint. IV iron formulation used in China was CosmoFer - given intravenously over a period of 4 to 6 hours	Placebo Group (China) n=17 Participants This group provides the outcome measurements for participants from the Fuwai site following their infusion of Placebo (saline, infused over 4-6hrs), whether this was at the first or second timepoint.	Ferinject Group (Europe) n=39 Participants IV iron formulation used in Europe - Ferinject (Intravenous, 1000 mg iron)- given over 15 minutes This group provides the outcome measurements for participants following their infusion of Ferinject, whether this was at the first or second timepoint	Placebo Group (Europe) n=39 Participants Placebo (saline) given intravenously over 15 minutes. This group provides the outcome measurements for participants following their infusion of Placebo, whether this was at the first or second timepoint
Stroke Volume (Cardiac Catheter)	55.11 mililitres Interval 49.57 to 61.15	54.65 mililitres Interval 45.22 to 63.17	77.87 mililitres Interval 77.41 to 102.05	99.71 mililitres Interval 75.86 to 102.02

SECONDARY outcome

Timeframe: 12 weeks

Cardiac MRI: Right ventricular end-diastolic volumes

Outcome measures

Measure	Cosmofer Group (China) This group provides the outcome measurements for participants following their infusion of CosmoFer, whether this was at the first or second timepoint. IV iron formulation used in China was CosmoFer - given intravenously over a period of 4 to 6 hours	Placebo Group (China) This group provides the outcome measurements for participants from the Fuwai site following their infusion of Placebo (saline, infused over 4-6hrs), whether this was at the first or second timepoint.	Ferinject Group (Europe) n=30 Participants IV iron formulation used in Europe - Ferinject (Intravenous, 1000 mg iron)- given over 15 minutes This group provides the outcome measurements for participants following their infusion of Ferinject, whether this was at the first or second timepoint	Placebo Group (Europe) n=30 Participants Placebo (saline) given intravenously over 15 minutes. This group provides the outcome measurements for participants following their infusion of Placebo, whether this was at the first or second timepoint
Cardiac Magnetic Resonance Imaging (MRI): Right Ventricular End-diastolic Volume	—	—	201.35 mililitres Interval 195.26 to 207.44	203.06 mililitres Interval 196.97 to 209.15

SECONDARY outcome

Timeframe: 12 weeks

Cardiac MR: Right ventricular end systolic volume

Outcome measures

Measure	Cosmofer Group (China) This group provides the outcome measurements for participants following their infusion of CosmoFer, whether this was at the first or second timepoint. IV iron formulation used in China was CosmoFer - given intravenously over a period of 4 to 6 hours	Placebo Group (China) This group provides the outcome measurements for participants from the Fuwai site following their infusion of Placebo (saline, infused over 4-6hrs), whether this was at the first or second timepoint.	Ferinject Group (Europe) n=30 Participants IV iron formulation used in Europe - Ferinject (Intravenous, 1000 mg iron)- given over 15 minutes This group provides the outcome measurements for participants following their infusion of Ferinject, whether this was at the first or second timepoint	Placebo Group (Europe) n=30 Participants Placebo (saline) given intravenously over 15 minutes. This group provides the outcome measurements for participants following their infusion of Placebo, whether this was at the first or second timepoint
Cardiac Magnetic Resonance Imaging (MRI): Right Ventricular End Systolic Volume (RVESV)	—	—	124.99 mililitres Interval 120.0 to 129.98	126.31 mililitres Interval 121.32 to 131.29

SECONDARY outcome

Timeframe: 12 weeks

Right ventricular stroke volumes assessed by cardiac MRI scan

Outcome measures

Measure	Cosmofer Group (China) This group provides the outcome measurements for participants following their infusion of CosmoFer, whether this was at the first or second timepoint. IV iron formulation used in China was CosmoFer - given intravenously over a period of 4 to 6 hours	Placebo Group (China) This group provides the outcome measurements for participants from the Fuwai site following their infusion of Placebo (saline, infused over 4-6hrs), whether this was at the first or second timepoint.	Ferinject Group (Europe) n=30 Participants IV iron formulation used in Europe - Ferinject (Intravenous, 1000 mg iron)- given over 15 minutes This group provides the outcome measurements for participants following their infusion of Ferinject, whether this was at the first or second timepoint	Placebo Group (Europe) n=30 Participants Placebo (saline) given intravenously over 15 minutes. This group provides the outcome measurements for participants following their infusion of Placebo, whether this was at the first or second timepoint
Cardiac Magnetic Resonance Imaging (MRI): Right Ventricular Stroke Volume (RVSV)	—	—	76.46 mililitres Interval 73.56 to 80.13	76.84 mililitres Interval 73.56 to 80.13

SECONDARY outcome

Timeframe: 12 weeks

Cardiac MR: Right ventricular ejection fractions

Outcome measures

Measure	Cosmofer Group (China) This group provides the outcome measurements for participants following their infusion of CosmoFer, whether this was at the first or second timepoint. IV iron formulation used in China was CosmoFer - given intravenously over a period of 4 to 6 hours	Placebo Group (China) This group provides the outcome measurements for participants from the Fuwai site following their infusion of Placebo (saline, infused over 4-6hrs), whether this was at the first or second timepoint.	Ferinject Group (Europe) n=30 Participants IV iron formulation used in Europe - Ferinject (Intravenous, 1000 mg iron)- given over 15 minutes This group provides the outcome measurements for participants following their infusion of Ferinject, whether this was at the first or second timepoint	Placebo Group (Europe) n=30 Participants Placebo (saline) given intravenously over 15 minutes. This group provides the outcome measurements for participants following their infusion of Placebo, whether this was at the first or second timepoint
Cardiac Magnetic Resonance Imaging (MRI): Right Ventricular Ejection Fraction (RVEF)	—	—	39.89 percentage Interval 38.55 to 41.23	39.64 percentage Interval 38.31 to 40.98

SECONDARY outcome

Timeframe: 12 weeks

Cardiac MR: Left Ventricular End Diastolic Volume

Outcome measures

Measure	Cosmofer Group (China) This group provides the outcome measurements for participants following their infusion of CosmoFer, whether this was at the first or second timepoint. IV iron formulation used in China was CosmoFer - given intravenously over a period of 4 to 6 hours	Placebo Group (China) This group provides the outcome measurements for participants from the Fuwai site following their infusion of Placebo (saline, infused over 4-6hrs), whether this was at the first or second timepoint.	Ferinject Group (Europe) n=30 Participants IV iron formulation used in Europe - Ferinject (Intravenous, 1000 mg iron)- given over 15 minutes This group provides the outcome measurements for participants following their infusion of Ferinject, whether this was at the first or second timepoint	Placebo Group (Europe) n=30 Participants Placebo (saline) given intravenously over 15 minutes. This group provides the outcome measurements for participants following their infusion of Placebo, whether this was at the first or second timepoint
Cardiac Magnetic Resonance Imaging (MRI): Left Ventricular End Diastolic Volume (LVEDV)	—	—	117.36 Mililitres Interval 113.47 to 121.26	118.33 Mililitres Interval 114.43 to 122.22

SECONDARY outcome

Timeframe: 12 weeks

Cardiac MR: Left Ventricular End Systolic Volume

Outcome measures

Measure	Cosmofer Group (China) This group provides the outcome measurements for participants following their infusion of CosmoFer, whether this was at the first or second timepoint. IV iron formulation used in China was CosmoFer - given intravenously over a period of 4 to 6 hours	Placebo Group (China) This group provides the outcome measurements for participants from the Fuwai site following their infusion of Placebo (saline, infused over 4-6hrs), whether this was at the first or second timepoint.	Ferinject Group (Europe) n=30 Participants IV iron formulation used in Europe - Ferinject (Intravenous, 1000 mg iron)- given over 15 minutes This group provides the outcome measurements for participants following their infusion of Ferinject, whether this was at the first or second timepoint	Placebo Group (Europe) n=30 Participants Placebo (saline) given intravenously over 15 minutes. This group provides the outcome measurements for participants following their infusion of Placebo, whether this was at the first or second timepoint
Cardiac Magnetic Resonance Imaging (MRI): Left Ventricular End Systolic Volume (LVESV)	—	—	43.90 Mililitres Interval 41.84 to 45.96	44.43 Mililitres Interval 42.37 to 46.49

SECONDARY outcome

Timeframe: 12 weeks

Cardiac MR: Left Ventricular Stroke Volume

Outcome measures

Measure	Cosmofer Group (China) This group provides the outcome measurements for participants following their infusion of CosmoFer, whether this was at the first or second timepoint. IV iron formulation used in China was CosmoFer - given intravenously over a period of 4 to 6 hours	Placebo Group (China) This group provides the outcome measurements for participants from the Fuwai site following their infusion of Placebo (saline, infused over 4-6hrs), whether this was at the first or second timepoint.	Ferinject Group (Europe) n=30 Participants IV iron formulation used in Europe - Ferinject (Intravenous, 1000 mg iron)- given over 15 minutes This group provides the outcome measurements for participants following their infusion of Ferinject, whether this was at the first or second timepoint	Placebo Group (Europe) n=30 Participants Placebo (saline) given intravenously over 15 minutes. This group provides the outcome measurements for participants following their infusion of Placebo, whether this was at the first or second timepoint
Cardiac Magnetic Resonance Imaging: Left Ventricular Stroke Volume (LVSV)	—	—	43.90 Mililitres Interval 41.84 to 45.96	73.96 Mililitres Interval 69.98 to 77.95

SECONDARY outcome

Timeframe: 12 weeks

Cardiac MR: Left Ventricular Ejection Fraction

Outcome measures

Measure	Cosmofer Group (China) This group provides the outcome measurements for participants following their infusion of CosmoFer, whether this was at the first or second timepoint. IV iron formulation used in China was CosmoFer - given intravenously over a period of 4 to 6 hours	Placebo Group (China) This group provides the outcome measurements for participants from the Fuwai site following their infusion of Placebo (saline, infused over 4-6hrs), whether this was at the first or second timepoint.	Ferinject Group (Europe) n=30 Participants IV iron formulation used in Europe - Ferinject (Intravenous, 1000 mg iron)- given over 15 minutes This group provides the outcome measurements for participants following their infusion of Ferinject, whether this was at the first or second timepoint	Placebo Group (Europe) n=30 Participants Placebo (saline) given intravenously over 15 minutes. This group provides the outcome measurements for participants following their infusion of Placebo, whether this was at the first or second timepoint
Cardiac Magnetic Resonance Imaging (MRI): Left Ventricular Ejection Fraction (LVEF)	—	—	63.10 Percentage Interval 61.38 to 64.81	62.94 Percentage Interval 61.22 to 64.65

SECONDARY outcome

Timeframe: 12 weeks

Cardiac MR: Left Ventricular Mass

Outcome measures

Measure	Cosmofer Group (China) This group provides the outcome measurements for participants following their infusion of CosmoFer, whether this was at the first or second timepoint. IV iron formulation used in China was CosmoFer - given intravenously over a period of 4 to 6 hours	Placebo Group (China) This group provides the outcome measurements for participants from the Fuwai site following their infusion of Placebo (saline, infused over 4-6hrs), whether this was at the first or second timepoint.	Ferinject Group (Europe) n=30 Participants IV iron formulation used in Europe - Ferinject (Intravenous, 1000 mg iron)- given over 15 minutes This group provides the outcome measurements for participants following their infusion of Ferinject, whether this was at the first or second timepoint	Placebo Group (Europe) n=30 Participants Placebo (saline) given intravenously over 15 minutes. This group provides the outcome measurements for participants following their infusion of Placebo, whether this was at the first or second timepoint
Cardiac Magnetic Resonance Imaging: Left Ventricular Mass	—	—	72.82 Grams Interval 70.82 to 74.82	73.53 Grams Interval 71.53 to 75.53

Adverse Events

European Dataset: Iron

Serious events: 4 serious events

Other events: 22 other events

Deaths: 26 deaths

European Dataset: Placebo

Serious events: 3 serious events

Other events: 21 other events

Deaths: 28 deaths

European Dataset: Outside Window

Serious events: 1 serious events

Other events: 11 other events

Deaths: 13 deaths

China Dataset: Iron

Serious events: 0 serious events

Other events: 3 other events

Deaths: 3 deaths

China Dataset: Placebo

Serious events: 1 serious events

Other events: 4 other events

Deaths: 4 deaths

China Dataset: Outside Window

Serious events: 0 serious events

Other events: 3 other events

Deaths: 2 deaths

Serious adverse events

Measure	European Dataset: Iron n=39 participants at risk IV iron formulation used in Europe - Ferinject - given over 15 minutes Ferinject or CosmoFer: Intravenous, 1000 mg iron Time scale is within 12 weeks from Ferinject administration	European Dataset: Placebo n=39 participants at risk Placebo was 1000mg saline: intravenous, no active drug Time scale is within 12 weeks from saline administration	European Dataset: Outside Window n=39 participants at risk AEs reported before intervention or more than 12 weeks following both Iron and Placebo.	China Dataset: Iron n=17 participants at risk IV iron formulation used in China - CosmoFer - over a period of 4 to 6 hours Ferinject or CosmoFer: Intravenous, 1000 mg iron Time scale is within 12 weeks from Ferinject administration	China Dataset: Placebo n=17 participants at risk Placebo was 1000mg saline: intravenous, no active drug Time scale is within 12 weeks from saline administration	China Dataset: Outside Window n=17 participants at risk AEs reported before intervention or more than 12 weeks following both Iron and Placebo.
Infections and infestations Device related infection	0.00% 0/39 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/39 • Adverse events collected from consent until the final follow-up visit at week 24.	2.6% 1/39 • Number of events 1 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.
Blood and lymphatic system disorders Hypophosphatemia	5.1% 2/39 • Number of events 2 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/39 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/39 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Haemorrhagic Ovarian Cyst	0.00% 0/39 • Adverse events collected from consent until the final follow-up visit at week 24.	2.6% 1/39 • Number of events 1 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/39 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.
Injury, poisoning and procedural complications Fall	2.6% 1/39 • Number of events 1 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/39 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/39 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.
Cardiac disorders Disease Progression	0.00% 0/39 • Adverse events collected from consent until the final follow-up visit at week 24.	2.6% 1/39 • Number of events 1 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/39 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.
Vascular disorders Para-spinal haematoma	0.00% 0/39 • Adverse events collected from consent until the final follow-up visit at week 24.	2.6% 1/39 • Number of events 1 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/39 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.
Infections and infestations Infection: Tonsillitis	2.6% 1/39 • Number of events 1 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/39 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/39 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.
Immune system disorders Allergic reaction	0.00% 0/39 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/39 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/39 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	5.9% 1/17 • Number of events 1 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.

Other adverse events

Measure	European Dataset: Iron n=39 participants at risk IV iron formulation used in Europe - Ferinject - given over 15 minutes Ferinject or CosmoFer: Intravenous, 1000 mg iron Time scale is within 12 weeks from Ferinject administration	European Dataset: Placebo n=39 participants at risk Placebo was 1000mg saline: intravenous, no active drug Time scale is within 12 weeks from saline administration	European Dataset: Outside Window n=39 participants at risk AEs reported before intervention or more than 12 weeks following both Iron and Placebo.	China Dataset: Iron n=17 participants at risk IV iron formulation used in China - CosmoFer - over a period of 4 to 6 hours Ferinject or CosmoFer: Intravenous, 1000 mg iron Time scale is within 12 weeks from Ferinject administration	China Dataset: Placebo n=17 participants at risk Placebo was 1000mg saline: intravenous, no active drug Time scale is within 12 weeks from saline administration	China Dataset: Outside Window n=17 participants at risk AEs reported before intervention or more than 12 weeks following both Iron and Placebo.
Infections and infestations Upper Respiratory Infection	2.6% 1/39 • Number of events 1 • Adverse events collected from consent until the final follow-up visit at week 24.	2.6% 1/39 • Number of events 1 • Adverse events collected from consent until the final follow-up visit at week 24.	2.6% 1/39 • Number of events 1 • Adverse events collected from consent until the final follow-up visit at week 24.	5.9% 1/17 • Number of events 1 • Adverse events collected from consent until the final follow-up visit at week 24.	17.6% 3/17 • Number of events 3 • Adverse events collected from consent until the final follow-up visit at week 24.	5.9% 1/17 • Number of events 1 • Adverse events collected from consent until the final follow-up visit at week 24.
General disorders Flu like symptoms	17.9% 7/39 • Number of events 9 • Adverse events collected from consent until the final follow-up visit at week 24.	12.8% 5/39 • Number of events 6 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/39 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.
General disorders Fatigue	10.3% 4/39 • Number of events 5 • Adverse events collected from consent until the final follow-up visit at week 24.	5.1% 2/39 • Number of events 2 • Adverse events collected from consent until the final follow-up visit at week 24.	7.7% 3/39 • Number of events 3 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.
General disorders Headache	0.00% 0/39 • Adverse events collected from consent until the final follow-up visit at week 24.	12.8% 5/39 • Number of events 5 • Adverse events collected from consent until the final follow-up visit at week 24.	2.6% 1/39 • Number of events 3 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.
Cardiac disorders Palpitations	0.00% 0/39 • Adverse events collected from consent until the final follow-up visit at week 24.	7.7% 3/39 • Number of events 3 • Adverse events collected from consent until the final follow-up visit at week 24.	2.6% 1/39 • Number of events 1 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.
Respiratory, thoracic and mediastinal disorders Epistaxis	2.6% 1/39 • Number of events 1 • Adverse events collected from consent until the final follow-up visit at week 24.	5.1% 2/39 • Number of events 2 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/39 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.
Ear and labyrinth disorders Vertigo	0.00% 0/39 • Adverse events collected from consent until the final follow-up visit at week 24.	5.1% 2/39 • Number of events 2 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/39 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.
General disorders Abdominal pain	7.7% 3/39 • Number of events 3 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/39 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/39 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.
Gastrointestinal disorders Diarrhoea	10.3% 4/39 • Number of events 5 • Adverse events collected from consent until the final follow-up visit at week 24.	5.1% 2/39 • Number of events 2 • Adverse events collected from consent until the final follow-up visit at week 24.	2.6% 1/39 • Number of events 1 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.
Gastrointestinal disorders Nausea	2.6% 1/39 • Number of events 1 • Adverse events collected from consent until the final follow-up visit at week 24.	5.1% 2/39 • Number of events 2 • Adverse events collected from consent until the final follow-up visit at week 24.	5.1% 2/39 • Number of events 2 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.
Infections and infestations Urinary tract infection	0.00% 0/39 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/39 • Adverse events collected from consent until the final follow-up visit at week 24.	5.1% 2/39 • Number of events 3 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.
Investigations Hypophosphataemia	17.9% 7/39 • Number of events 8 • Adverse events collected from consent until the final follow-up visit at week 24.	2.6% 1/39 • Number of events 1 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/39 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.
Cardiac disorders Cardiac chest pain	0.00% 0/39 • Adverse events collected from consent until the final follow-up visit at week 24.	2.6% 1/39 • Number of events 1 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/39 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	5.9% 1/17 • Number of events 1 • Adverse events collected from consent until the final follow-up visit at week 24.
Gastrointestinal disorders Periodontal disease	0.00% 0/39 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/39 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/39 • Adverse events collected from consent until the final follow-up visit at week 24.	5.9% 1/17 • Number of events 1 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.
General disorders Non-cardiac chest pain	0.00% 0/39 • Adverse events collected from consent until the final follow-up visit at week 24.	5.1% 2/39 • Number of events 2 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/39 • Adverse events collected from consent until the final follow-up visit at week 24.	5.9% 1/17 • Number of events 1 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.
General disorders Allergic reaction	0.00% 0/39 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/39 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/39 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	5.9% 1/17 • Number of events 1 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.
Investigations Elevated NT-Pro BNP	0.00% 0/39 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/39 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/39 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	5.9% 1/17 • Number of events 1 • Adverse events collected from consent until the final follow-up visit at week 24.
Injury, poisoning and procedural complications Bruising	2.6% 1/39 • Number of events 1 • Adverse events collected from consent until the final follow-up visit at week 24.	5.1% 2/39 • Number of events 2 • Adverse events collected from consent until the final follow-up visit at week 24.	5.1% 2/39 • Number of events 2 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.
Nervous system disorders Dysguesia	5.1% 2/39 • Number of events 2 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/39 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/39 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.1% 2/39 • Number of events 2 • Adverse events collected from consent until the final follow-up visit at week 24.	2.6% 1/39 • Number of events 1 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/39 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.
Infections and infestations Productive cough	0.00% 0/39 • Adverse events collected from consent until the final follow-up visit at week 24.	2.6% 1/39 • Number of events 1 • Adverse events collected from consent until the final follow-up visit at week 24.	5.1% 2/39 • Number of events 2 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.
Infections and infestations Lung infection	5.1% 2/39 • Number of events 2 • Adverse events collected from consent until the final follow-up visit at week 24.	2.6% 1/39 • Number of events 1 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/39 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.	0.00% 0/17 • Adverse events collected from consent until the final follow-up visit at week 24.

Additional Information

Professor Martin Wilkins

Imperial College London

Phone: 0203 313 8078

Email: jacob.bonner@nhs.net

Results disclosure agreements

• Principal investigator is a sponsor employee Any publications should be agreed in advance by the sponsor via the Chief Investigator. Publications will be written by Chief investigator with contributions from collaborating investigators acknowledged appropriately (e.g. via authorship). Trial agreements between sponsor and participating site provide full details of publication restrictions and review timelines.
• Publication restrictions are in place

Restriction type: OTHER