Orally inhaled heparin in patients with cystic fibrosis (CF)

Plain English Summary

Not provided at time of registration

Trial website

Type

Scientific

Primary contact

Dr Mark J Main

ORCID ID

Contact details

Vectura Limited (UK)
1 Prospect West
Chippenham
SN14 6FH
United Kingdom
+44 (0)1249 667 700
mark.main@vectura.com

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

VR496/005

Scientific title

A phase I/II randomised, placebo-controlled, double blind trial to assess the safety, tolerability, pharmacodynamics and exploratory efficacy of heparin inhalation in patients with cystic fibrosis (CF)

Acronym

Study hypothesis

Orally inhaled Heparin is expected to provide advantages over currently available treatments for cystic fibrosis (CF) in a patient convenient delivery system.

Ethics approval

1. Multi-Centre Research Ethics Committee for Wales (UK) gave approval on 18th March 2008
2. Irish Ethics Committee (St Vincent's Healthcare Group Ltd Ethics) approved the study on 11th November 2008
Added 20/04/2010
3. Polish Ethics Committee (Bioethics Committee of the Medical University, Lodz) final approval gained on the 14th July 2009 (previously stated as the 21st April 2009)
4. Italian Central Ethics Committee (Comitato Etico, Azienda Ospedaliera Universitaria Integrata, Verona, approved on the 13th April 2010
Added 07/06/2010
5. Bellberry Human Research Ethics Committee, Dulwich, South Australia approved on the 20th April 2010

Study design

Randomised double blind placebo controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Condition

Cystic fibrosis

Intervention

Patients will be randomised to receive one of three daily dose levels of heparin treatment or matching placebo; to be self-administered by inhalation by the patient twice daily for four consecutive weeks. Nominal Daily Doses to be studied are: 11400 IU, 22800 IU and 45600 IU.

For each patient there will be a screening period of 4 weeks, a treatment period of 4 weeks with a follow-up period of 2 weeks.

Intervention type

Drug

Phase

Phase I/II

Drug names

Heparin inhalation powder

Primary outcome measure

Safety and tolerability.

Timepoints:
Five visits to the trial centre are included: screening, baseline, week 2, week 4 and, for follow-up, week 6.

Secondary outcome measures

Assessment of:
1. Sputum properties (i.e., rheological viscoelasticity/physicochemical measurement parameters)
2. Sputum inflammatory markers
3. Exhaled breath condensate pH
4. Blood plasma inflammatory markers
5. Blood coagulation
6. Visual Analogue Scale (VAS) parameters
7. Sputum microbiology
8. Pulmonary function parameters including FEV1 and forced vital capacity (FVC)
9. Response to the Cystic Fibrosis Questionnaire

Timepoints:
Five visits to the trial centre are included: screening, baseline, week 2, week 4 and, for follow-up, week 6.

Overall trial start date

01/11/2008

Overall trial end date

30/11/2010

Reason abandoned (if study stopped)

Participant inclusion criteria

Amendment as of 20/04/2010:
Point one below has been amended as follows:
1. Male or female, aged 16 years or older

Current information as of 21/09/2009:
1. Male or female, aged 18 years or older
2. Non-smoker
3. Written informed consent obtained prior to any trial specific procedures
4. Confirmed diagnosis of CF lung disease (i.e., respiratory clinical symptoms and positive sweat test or disease inducing mutations) by CF expert/investigator
5. Forced expiratory volume in one second (FEV1) at 40 - 90% of predicted value for age, sex and height at screening and baseline
6. FEV1 value at Baseline is within +/-15% of value at screening
7. Regular mucus production due to CF
8. Ease of sputum expectoration as defined by VAS score of ≤ 80 mm
9. Inflammatory markers above upper limit of normal range.
10. Adequate contraceptive measures.
11. Able to comply with all protocol requirements
12. Able to use inhalation device.

Amended as of 17/04/2009:
Please note that point 5 of the below criteria has been amended to read:
5. Forced expiratory volume in one second (FEV1) at 40 - 90% of predicted value for age, sex and height at screening and baseline

Initial information at time of registration:
1. Male or female, aged 18 years or older
2. Non-smoker
3. Written informed consent obtained prior to any trial specific procedures
4. Confirmed diagnosis of CF lung disease (i.e., respiratory clinical symptoms and positive sweat test or disease inducing mutations) by CF expert/investigator
5. Forced expiratory volume in one second (FEV1) at 40 - 80% of predicted value for age, sex and height during six months prior to screening
6. FEV1 within 10% of best value during six months prior to screening
7. Regular mucus production due to CF

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

64

Participant exclusion criteria

Initial information at time of registration:
To be eligible for inclusion into this trial, each patient must not violate any one of the following exclusion criteria at the time of screening, at the time of assessment or as specifically described below:
1. Any contraindication to Monoparin® considered clinically relevant
2. Increased bleeding risk
3. History of heparin-induced thrombocytopaenia
4. Patients with bleeding diathesis
5. Evidence of portal hypertension (e.g., hypersplenism or known grade III/IV oesophageal varices)
6. Clinically significant liver disease
7. Pregnancy at screening, or lactation
8. Previous thoracic or scheduled major surgery during trial
9. Any regular anticoagulant therapy (e.g., warfarin, aspirin) in the two weeks prior to screening
10. Modification of medication to treat respiratory disease between screening and baseline (Day 1)

Added 17/04/2009:
11. Diagnosis or history of aspergilloma

Added 21/09/2009:
12. Clinically significant serious disease or organ system disease not currently controlled / stable on present therapy
13. Planned hospitalisations which could interfere with trial compliance
14. Unable for any other reason to satisfactorily comply with the protocol (e.g., attendance for trial visits, treatment or assessments)

Recruitment start date

01/11/2008

Recruitment end date

30/11/2010

Countries of recruitment

Ireland, Italy, Poland, United Kingdom

Trial participating centre

Vectura Limited (UK)
Chippenham
SN14 6FH
United Kingdom

Organisation

Vectura Limited (UK)

Sponsor details

c/o Dr Mark J Main
1 Prospect West
Chippenham
SN14 6FH
United Kingdom
+44 (0)1249 667 700
mark.main@vectura.com

Sponsor type

Industry

Website

http://www.vectura.com/

Funder type

Industry

Funder name

Vectura Limited (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Basic results (scientific)

Publication list

Publication citations

08/08/21016: No publications found in PubMed, verifying study status with principal investigator. 07/06/10: Details of further ethics approval have been added. Please refer to the ethics approval field below for more details. 20/04/2010: This record has been updated to include changes to the trial protocol due to an extension to the age range of participants. At this time, the anticipated end date of this trial was also extended; the previous anticipated end date of this trial was 31/10/2009. Italy was also added to the countries of recruitment at this time. All changes can be found in the relevant field with the above update date. Please also note that due to this change in protocol, the titles of this trial have been amended slightly to read 'patients' instead of 'adults'. 21/09/2009: this record has been updated to include amendments to the inclusion criteria, and ethics approval. The screening period has been amended from 2-4 weeks to 4 weeks and Poland has been added to the countries of recruitment. 17/04/2009: This record has been updated to include amendments to the inclusion and exclusion criteria, details of which can be found in the relevant fields.