NCT02040584 (REDUCE) is a Phase 3 clinical trial of Minimisation of TAC in Liver Transplant, sponsored by Novartis Pharmaceuticals.

Who is sponsoring NCT02040584?

NCT02040584 is sponsored by Novartis Pharmaceuticals.

What drugs are being tested in NCT02040584?

Interventions in NCT02040584: Minimisation of TAC, TAC + MMF + corticosteroids.

What condition does NCT02040584 study?

NCT02040584 studies Liver Transplant.

Is NCT02040584 still recruiting?

NCT02040584 is currently completed. Last updated 13 June 2019.

Are results published for NCT02040584?

Yes — primary outcome results have been posted to ClinicalTrials.gov. See the outcomes section above for details.

Last reviewed 2019-06-13 · How we verify

NCT02040584: REDUCE

Name: Drug Landscape Pharmaceutical Database
Creator: Drug Landscape
Published: 2026-01-01
License: https://creativecommons.org/licenses/by/4.0/

A Multicentre, Randomised, Open-label, Controlled, 12-month Follow-up Study to Assess Impact on Renal Function of an Immunosuppression Regimen Based on Tacrolimus Minimisation in Association With Everolimus in de Novo Liver Transplant Recipients.

Completed Phase 3 Results posted Last updated 13 June 2019

What this trial tests

Phase 3 trial testing Minimisation of TAC in Liver Transplant in 217 participants. Completed in 10 February 2016.

Timeline

20 December 2013

Primary endpoint
10 February 2016

10 February 2016

Quick facts

Lead sponsor	Novartis Pharmaceuticals
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	217
Start date	20 December 2013
Primary completion	10 February 2016
Estimated completion	10 February 2016
Sites	20 locations across Spain

Drugs / interventions tested

Minimisation of TAC — full drug profile →
TAC + MMF + corticosteroids — full drug profile →

Conditions studied

Liver Transplant — all drugs for Liver Transplant →

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

Adults 18 to 70, any sex, with Liver Transplant. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentages of Participants Showing Clinical Benefit by Renal Function Stratification Primary · week 4, week 52.

Clinical benefit is defined as: • an improvement in 1 or 2 ranges of the eGFR, according to MDRD-4 at Week 52 post-transplant in patients with values of 30-\<45 or 45-\<60 mL/min/1.73 m2 in Week 4. or • stabilisation of eGFR in patients with values ≥60 mL/min/1.73 m2 at Week 4 and maintained at Week 52 post-transplant.

> = 30 - 45 ml/min/1.73m^2 at Week 52

Group	Value	95% CI
Experimental Group	4.76
Control Group	3.77

> = 45 - <60 ml/min/1.73m^2 at Week 52

Group	Value	95% CI
Experimental Group	14.29
Control Group	16.04

> = 60 ml/min/1.73m^2 at Week 52

Group	Value	95% CI
Experimental Group	79.05
Control Group	79.25

Changes in Creatinine Clearance - Cockcroft-Gault Formula Secondary · Screening visit (transplant), weeks 1,4,12,24,36 and 52 post-transplant

Kidney function was assessed over time by creatine clearance based on the Cockcroft-Gault formula. Estimated creatinine clearance (mL/min) = \[(140 - age) x (weight) x (0.85 if female)\] / (72 x serum creatinine). Units: age (years); weight (kg); serum creatinine (mg/dL). The values of the eGFR according to the creatinine clearance (Cockcroft-Gault formula) for the ITT population were ml/min/1.73 m\^2.

Screening

Group	Value	95% CI
Experimental Group	104.67	± 36.40
Control Group	109.69	± 48.47

Week 1

Group	Value	95% CI
Experimental Group	116.93	± 44.82
Control Group	118.09	± 44.82

Week 4

Group	Value	95% CI
Experimental Group	80.19	± 28.00
Control Group	91.26	± 37.60

Week 12

Group	Value	95% CI
Experimental Group	87.76	± 26.51
Control Group	90.14	± 35.82

Week 24

Group	Value	95% CI
Experimental Group	89.57	± 32.89
Control Group	87.93	± 35.92

Week 36

Group	Value	95% CI
Experimental Group	94.46	± 30.26
Control Group	90.91	± 35.96

Week 52

Group	Value	95% CI
Experimental Group	92.21	± 29.96
Control Group	91.04	± 37.26

Changes in eGFR Based on the MDRD-4 Formula Secondary · Screening visit (transplant), weeks 1,4,12,24,36 and 52 post-transplant

Kidney function was assessed over time by changes in eGFR according to the MDRD-4 formula. The MDRD-4 formula (Levey et al., 2000) was used based on serum concentration of creatinine (conventional units): eGFR (mL/min/1.73 m2) = 186 x (serum creatinine)-1.154 x (age)-0.203 x (0.742 if female) x (1.210 if of African descent). Units: serum creatinine (mg/dL); age (years).

Screening

Group	Value	95% CI
Experimental Group	100.20	± 38.74
Control Group	99.42	± 43.09

Week 1

Group	Value	95% CI
Experimental Group	112.86	± 50.06
Control Group	112.15	± 48.16

Week 4

Group	Value	95% CI
Experimental Group	82.18	± 28.47
Control Group	88.39	± 34.32

Week 12

Group	Value	95% CI
Experimental Group	85.99	± 25.13
Control Group	83.57	± 28.19

Week 24

Group	Value	95% CI
Experimental Group	86.02	± 31.97
Control Group	82.00	± 26.93

Week 36

Group	Value	95% CI
Experimental Group	87.68	± 32.49
Control Group	83.04	± 25.56

Week 52

Group	Value	95% CI
Experimental Group	86.09	± 27.87
Control Group	83.23	± 25.24

eGFR Values(MDRD-4 Formula) According to the MELD Score Secondary · Screening visit (transplant), weeks 1,4,12,24,36 and 52 post-transplant

Model for End Stage Liver Disease (MELD) score: ≤14, 15-19, 20-24, 25-29, ≥30. The higher the number indicates the urgency for transplant.

Screening

Group	Value	95% CI
<= 14	96.63	76.31 – 119.50
15 to 19	90.29	65.64 – 114.92
20 to 24	88.89	70.03 – 114.67
25 to 29	104.45	93.21 – 123.90
> = 30	38.35	38.35 – 38.35
<= 14 Control Group	102.27	75.09 – 120.19
15 to 19 Control Group	93.85	73.93 – 123.19
20 to 24 Control Group	91.45	68.74 – 116.49
25 to 29 Control Group	99.50	19.76 – 137.89
> = 30 Control Group	53.73	38.82 – 66.97

Week 1

Group	Value	95% CI
<= 14	114.00	94.24 – 142.51
15 to 19	93.31	76.61 – 127.75
20 to 24	83.45	66.76 – 114.06
25 to 29	137.61	124.30 – 148.67
> = 30	82.04	82.04 – 82.04
<= 14 Control Group	108.64	83.22 – 138.55
15 to 19 Control Group	92.98	55.41 – 129.49
20 to 24 Control Group	119.19	100.53 – 147.60
25 to 29 Control Group	156.41	29.81 – 184.87
> = 30 Control Group	86.45	57.98 – 117.96

Week 4

Group	Value	95% CI
<= 14	81.37	63.46 – 92.20
15 to 19	85.19	66.09 – 99.26
20 to 24	70.57	51.90 – 99.02
25 to 29	75.94	50.93 – 121.86
> = 30	69.43	69.43 – 69.43
<= 14 Control Group	89.44	62.78 – 107.55
15 to 19 Control Group	72.76	51.64 – 113.93
20 to 24 Control Group	89.67	63.89 – 133.44
25 to 29 Control Group	85.23	42.83 – 109.13
> = 30 Control Group	78.57	51.47 – 108.61

Week 12

Group	Value	95% CI
<= 14	85.81	64.65 – 98.87
15 to 19	88.76	65.92 – 118.20
20 to 24	83.91	68.46 – 94.96
25 to 29	94.82	50.94 – 106.28
> = 30	56.67	56.67 – 56.67
<= 14 Control Group	83.63	69.33 – 101.35
15 to 19 Control Group	67.00	48.31 – 99.84
20 to 24 Control Group	87.22	67.63 – 107.01
25 to 29 Control Group	65.01	43.15 – 96.53
> = 30 Control Group	81.92	58.33 – 87.43

Week 24

Group	Value	95% CI
<= 14	80.76	64.37 – 107.89
15 to 19	81.41	57.22 – 104.86
20 to 24	78.88	62.22 – 94.68
25 to 29	84.86	68.54 – 101.19
> = 30	60.37	60.37 – 60.37
<= 14 Control Group	80.01	66.16 – 97.47
15 to 19 Control Group	70.27	55.26 – 93.99
20 to 24 Control Group	82.64	65.25 – 113.80
25 to 29 Control Group	88.34	30.17 – 104.72
> = 30 Control Group	62.74	47.46 – 75.65

Week 36

Group	Value	95% CI
<= 14	81.96	64.82 – 111.44
15 to 19	92.44	68.05 – 113.18
20 to 24	75.62	61.64 – 100.46
25 to 29	83.09	55.72 – 110.46
> = 30	58.07	58.07 – 58.07
<= 14 Control Group	86.72	72.09 – 97.40
15 to 19 Control Group	67.90	54.34 – 90.95
20 to 24 Control Group	86.17	68.59 – 107.21
25 to 29 Control Group	68.32	57.01 – 79.63
> = 30 Control Group	65.58	45.11 – 73.55

Week 52

Group	Value	95% CI
<= 14	86.14	66.70 – 101.59
15 to 19	88.94	65.24 – 114.50
20 to 24	71.60	62.48 – 89.66
25 to 29	83.94	60.69 – 107.20
> = 30	53.93	53.93 – 53.93
<= 14 Control Group	80.92	68.98 – 104.03
15 to 19 Control Group	70.32	54.12 – 82.38
20 to 24 Control Group	90.66	74.52 – 113.18
25 to 29 Control Group	74.82	69.00 – 80.63
> = 30 Control Group	63.26	45.52 – 79.77

Urine Protein/Creatinine Ratio Secondary · Screening visit, week 1,4,18,24, and 52

The urine protein/creatinine ratio was assessed throughout follow-up in both treatment groups.

Screening

Group	Value	95% CI
Experimental Group	199.89	± 582.03
Control Group	131.56	± 178.95

Week 1

Group	Value	95% CI
Experimental Group	252.48	± 308.22
Control Group	349.46	± 396.44

Week 4

Group	Value	95% CI
Experimental Group	134.77	± 175.05
Control Group	141.71	± 187.11

Week 18

Group	Value	95% CI
Experimental Group	204.26	± 688.05
Control Group	105.02	± 79.61

Week 24

Group	Value	95% CI
Experimental Group	200.17	± 466.55
Control Group	120.52	± 108.04

Week 52

Group	Value	95% CI
Experimental Group	219.41	± 406.52
Control Group	143.05	± 220.72

Percentage of Participants With Incidence of Proteinuria Secondary · Screening visit, week 1,4,18,24, and 52

The incidence of proteinuria (≥0.5-0.9 g/day, ≥1.0-2.9 g/day and ≥3.0 g/day) was assessed throughout follow-up in both treatment groups. Proteinuria was defined as protein/creatinine ratio ≥ 0.5.

≥ 0.5-1.0 g/day at screening

Group	Value	95% CI
Experimental Group	0.00
Control Group	3.77

≥ 1.0-3.0 g/day at screening

Group	Value	95% CI
Experimental Group	2.00
Control Group	1.89

≥ 3.0 g/day at screening

Group	Value	95% CI
Experimental Group	2.00
Control Group	0.00

≥ 0.5-1.0 g/day at Week 1

Group	Value	95% CI
Experimental Group	3.23
Control Group	18.31

≥ 1.0-3.0 g/day at Week 1

Group	Value	95% CI
Experimental Group	6.45
Control Group	5.63

≥ 3.0 g/day at Week 1

Group	Value	95% CI
Experimental Group	0.00
Control Group	0.00

≥ 0.5-1.0 g/day at Week 4

Group	Value	95% CI
Experimental Group	5.21
Control Group	1.05

≥ 1.0-3.0 g/day at Week 4

Group	Value	95% CI
Experimental Group	0.00
Control Group	1.05

Percentage of Participants With Acute Rejection, BPAR, and Treated BPAR Secondary · Throughout the study period, approximately 2 years and 2 months

Liver biopsy had to be performed in all cases where acute rejection was suspected. Results of the biopsy were interpreted by the local pathologist (who did not known the treatment given to the patient) according to the Banff classification (1997). Biopsy-proven acute rejection (BPAR) defined as clinical suspicion of acute rejection confirmed in biopsy. Treated BPAR was deemed to be an episode of acute rejection in which the interpretation of the local pathologist showed that it reached any grade of acute rejection under the Banff classification, and for which anti-rejection therapy was admin

Patients with suspected acute rejection

Group	Value	95% CI
Experimental Group	17.14
Control Group	15.09

Patients with BPAR

Group	Value	95% CI
Experimental Group	5.71
Control Group	3.77

Patients with treated BPAR

Group	Value	95% CI
Experimental Group	4.76
Control Group	1.89

Time to Rejection Secondary · Throughout study period, approximately 2 years and 2 months

Time to acute rejection was calculated from the date of transplantation. Acute rejection date was taken from biopsy date, as the date of rejection was not collected. Time to treated BPAR was calculated from the date of transplantation.

Time to acute rejection

Group	Value	95% CI
Experimental Group	3.74	± 3.15
Control Group	2.91	± 2.89

Time to treated BPAR

Group	Value	95% CI
Experimental Group	2.65	± 1.50
Control Group	3.85	± 5.25

Severity of Rejection Secondary · Throughout study period, approximately 2 years and 2 months

Severity of acute rejection and treated BPAR was graded according to Banff criteria. Grade of acute rejection according to Banff criteria: mild, moderate, severe.

Severity of acute rejection: Mild (Grade I)

Group	Value	95% CI
Experimental Group	13.64	± 3.15
Control Group	11.11	± 2.89

Severity of acute rejection: Moderate(Grade II)

Group	Value	95% CI
Experimental Group	13.64	± 1.50
Control Group	5.56	± 5.25

Severity of acute rejection: Severe(Grade III)

Group	Value	95% CI
Experimental Group	0.00
Control Group	5.56

Severity of treated BPAR: Mild (Grade I)

Group	Value	95% CI
Experimental Group	33.33
Control Group	0.00

Severity of treated BPAR: Moderate(Grade II)

Group	Value	95% CI
Experimental Group	50.00
Control Group	50.00

Severity of treated BPAR: Severe(Grade III)

Group	Value	95% CI
Experimental Group	0.00
Control Group	50.00

Percentages of Participants With HCV-positive and HCV Genotype Secondary · approximately 2 years and 2 months

The viral load of HCV-RNA and HCV genotype was assessed in HCV-positive patients. The term "genotype" was used to describe strains of HCV that vary but were related to the virus. Worldwide, there were 11 primary groups of HCV genotypes designated by the numbers from 1-11, with the most common in our setting being subtypes 1a, 1b, 2 and 3, which were identified in the local laboratory according to their usual testing methods.

Hepatitis C virus (HVC) positive

Group	Value	95% CI
Experimental Group	33.33
Control Group	36.79

HCV genotype 01

Group	Value	95% CI
Experimental Group	80.00
Control Group	76.92

HCV genotype 03

Group	Value	95% CI
Experimental Group	17.14
Control Group	10.26

HCV genotype 04

Group	Value	95% CI
Experimental Group	2.86
Control Group	2.56

Concentration of p-P70S6K Secondary · weeks 6,8,12,18,24,36,52 at 0 (Cmin), and 1 (C1h) hrs post-dose.

the biomarker of personal response to everolimus, monitoring of the activity of the target, kinase P70 S6, in its phosphorylated form at Thr389. EVR=everolimus Cmin=minimum concentration

Cmin EVR week 6

Group	Value	95% CI
Experimental Group	3.8	± 1.7

C1h EVR week 6

Group	Value	95% CI
Experimental Group	6.8	± 6.3

Cmin EVR week 8

Group	Value	95% CI
Experimental Group	4.7	± 1.6

C1h EVR week 8

Group	Value	95% CI
Experimental Group	9.5	± 4.9

Cmin EVR week 12

Group	Value	95% CI
Experimental Group	4.4	± 1.8

C1h EVR week 12

Group	Value	95% CI
Experimental Group	16	± 9.5

Cmin EVR week 18

Group	Value	95% CI
Experimental Group	6.8	± 2.7

C1h EVR week 18

Group	Value	95% CI
Experimental Group	14.6	± 6.7

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 2 years and 2 month.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Experimental Group

Serious: 55/106 (52%)

Deaths: —

Control Group

Serious: 48/109 (44%)

Deaths: —

Serious adverse events (152 terms)

Reaction	System	Experimental Group	Control Group
Pyrexia	General disorders	—	—
Hepatitis C	Infections and infestations	—	—
Respiratory tract infection	Infections and infestations	—	—
Ascites	Gastrointestinal disorders	—	—
Bile duct stenosis	Hepatobiliary disorders	—	—
Post procedural bile leak	Injury, poisoning and procedural complications	—	—
Endoscopic retrograde cholangiopancreatography	Investigations	—	—
Abdominal pain	Gastrointestinal disorders	—	—
Inguinal hernia	Gastrointestinal disorders	—	—
Cholestasis	Hepatobiliary disorders	—	—
Complications of transplanted liver	Injury, poisoning and procedural complications	—	—
Renal failure	Renal and urinary disorders	—	—
Anaemia	Blood and lymphatic system disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Asthenia	General disorders	—	—
Oedema peripheral	General disorders	—	—
Bile duct stone	Hepatobiliary disorders	—	—
Cholangitis acute	Hepatobiliary disorders	—	—
Hepatic artery thrombosis	Hepatobiliary disorders	—	—
Hepatitis cholestatic	Hepatobiliary disorders	—	—
Jaundice	Hepatobiliary disorders	—	—
Liver transplant rejection	Immune system disorders	—	—
Cytomegalovirus viraemia	Infections and infestations	—	—
Liver abscess	Infections and infestations	—	—

Other adverse events (42 terms — click to expand)

Reaction	System	Experimental Group	Control Group
Oedema peripheral	General disorders	—	—
Anaemia	Blood and lymphatic system disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Hypertension	Vascular disorders	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—
Ascites	Gastrointestinal disorders	—	—
Cholestasis	Hepatobiliary disorders	—	—
Tremor	Nervous system disorders	—	—
Pyrexia	General disorders	—	—
Hyperglycaemia	Metabolism and nutrition disorders	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Insomnia	Psychiatric disorders	—	—
Pleural effusion	Respiratory, thoracic and mediastinal disorders	—	—
Asthenia	General disorders	—	—
Renal failure	Renal and urinary disorders	—	—
Renal impairment	Renal and urinary disorders	—	—
Leukopenia	Blood and lymphatic system disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Diabetes mellitus	Metabolism and nutrition disorders	—	—
Hypercholesterolaemia	Metabolism and nutrition disorders	—	—
Neutropenia	Blood and lymphatic system disorders	—	—
Headache	Nervous system disorders	—	—
Abdominal pain	Gastrointestinal disorders	—	—
Dyslipidaemia	Metabolism and nutrition disorders	—	—
Proteinuria	Renal and urinary disorders	—	—
Transaminases increased	Investigations	—	—
Hypomagnesaemia	Metabolism and nutrition disorders	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—
Ileus paralytic	Gastrointestinal disorders	—	—
Oedema	General disorders	—	—
Urinary tract infection	Infections and infestations	—	—
Leukocytosis	Blood and lymphatic system disorders	—	—
Hypertriglyceridaemia	Metabolism and nutrition disorders	—	—
Anxiety	Psychiatric disorders	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—
Jaundice	Hepatobiliary disorders	—	—
Hepatitis C	Infections and infestations	—	—
Cell death	Metabolism and nutrition disorders	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—

Most-reported serious reactions: Pyrexia, Hepatitis C, Respiratory tract infection, Ascites, Bile duct stenosis, Post procedural bile leak, Endoscopic retrograde cholangiopancreatography, Abdominal pain.

Data from ClinicalTrials.gov NCT02040584 adverse events section.

Sponsor's own description

Assuming greater efficacy in the prevention of acute rejection in the EVR arm with minimisation of TAC levels, the hypothesis of the present trial was that the introduction of EVR in combination with the minimisation of TAC (rTAC) may offer improved kidney function compared with standard therapy with TAC-MMF.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.

Verify or expand the search:

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Verify against primary sources

ClinicalTrials.gov — authoritative US registry record
WHO ICTRP — international registry index
EU Clinical Trials Register
Sponsor press releases (Google)

Data sources for this page

Trial protocol + status: ClinicalTrials.gov NCT02040584 (US National Library of Medicine, public domain)
Drug + disease cross-links: matched in real time against Drug Landscape's normalised drug + company + condition tables
Sponsor: as reported to ClinicalTrials.gov by Novartis Pharmaceuticals
Last refreshed: 13 June 2019

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02040584.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing

NCT02040584: REDUCE

Quick facts

Drugs / interventions tested

Conditions studied

Sponsor

Who can join

Results — posted to ClinicalTrials.gov

Adverse events — posted to ClinicalTrials.gov

Serious adverse events (152 terms)

Sponsor's own description

Publications & conference data

Related trials

Other recruiting trials for Liver Transplant

Other Novartis Pharmaceuticals trials

Verify against primary sources