Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT01937650 |
| Other study ID # |
2009-059 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 2/Phase 3
|
| First received |
August 30, 2013 |
| Last updated |
September 4, 2013 |
| Start date |
June 2009 |
| Est. completion date |
April 2010 |
Study information
| Verified date |
September 2013 |
| Source |
Makerere University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The objective of the study was to determine whether there was a difference in the
effectiveness of Radiotherapy alone compared with Radiotherapy plus Metronidazole in the
treatment of women with advanced cancer of the cervix in Mulago hospital. It was a randomized
controlled trial composed of 38 women altogether, with one group composed of randomly
selected women with advanced cancer of the cervix treated with radiotherapy alone and the
other group composed of similar women but treated with radiotherapy and metronidazole.
Description:
Methods A double blinded placebo controlled trial was used to determine the efficacy and
safety of metronidazole as an adjunct to radiotherapy compared to radiotherapy alone for the
treatment of anemic patients with advanced cancer of the cervix as measured by clinical
response.
The unit of randomization was a woman with cancer of the cervix from stage IIIB to IVB and
hemoglobin level of 12g/dl or less. The ones who consented to the study were enrolled and
randomized to either the radiotherapy and metronidazole (RT+MX) or the radiotherapy and
placebo (RT) arms.
The study was conducted in both the Department of Radiotherapy and the Department of
Obstetrics and Gynecology of Mulago hospital, Kampala, Uganda.
Women eligible for inclusion in the study were those with cancer of the cervix who had
histologically proven stage IIB to IVB, fit for radiotherapy and an Hb of 12g/dl or less.
Women taking metronidazole treatment for other reasons other than radio-sensitization and
those with a history of neuropathy or with hypersensitivity to metronidazole were excluded.
A randomization code was generated by an independent statistician who did not participate in
the study nor visit the study site. The randomization code was then placed in an opaque and
sealed envelope and sent a copy to the pharmacist in the study centre so that he got to know
what to put in each envelope for study participants. The envelopes were kept by the study
pharmacist who dispensed the drugs. The code was to be broken when the principal investigator
felt that the blinded treatment was harmful to the patient, either because of the side
effects or failure to respond in which case he would urgently notify the data safety and
review board with the view of breaking the code for that particular patient.
The total number of study participants was 40. In view of the need for equal numbers at
equally spaced points in the sequence of the study, random permuted blocks of four patients
each were used. Letter A was used for Radiotherapy & Metronidazole (RT+MX) and B for
Radiotherapy alone (RT) assignment. The blocks were as follows:
AABB - block number 1 ABBA- block number 2 BBAA - block number 3 ABAB - block number 4 BAAB -
block number 5 BABA - block number 6 Treatment modalities included radiotherapy
administration plus Metronidazole or paracetamol administration. Radiotherapy administration
was in two phases using tele-therapy and brachy-therapy. The first phase was tele-therapy via
parallel-opposed portals (half the dose in antero-posterior and the other half in the
postero-anterior direction) from Co-60 radiation source, with a total dose of 50 Gy given in
25 fractions of 2 Gy/day (Monday to Friday and weekend rest) for five weeks. The patients
were then given a break of 1-4 weeks before getting the second phase of treatment. The second
phase was brachy-therapy from a Cs-137 source, whereby a single dose of 30Gy was delivered at
point A at a rate of 2.55 Gy/ hour for 7 hours and 50 minutes, via a uterine Tandem and two
vaginal Ovoids. In case of severe vaginal stenosis during the first phase, a cylindrical
applicator would be used.
Participants in the study arm received 1gm (two suppositories) of metronidazole per rectum 30
minutes before radiotherapy for every other radiotherapy session and it was omitted in the
two rest days of Saturday and Sunday. Participants in the control arm received 500mg (two
suppositories) of paracetamol as a placebo on similar days. The study was conducted during
day time.
The metronidazole and paracetamol suppositories looked identical in colour, smell and shape.
Although the packaging was similar it had different labels. They were therefore dispensed
when ready to use and out of the packaging and each patient got two suppositories in a
session.
Subjective assessment of the clinical symptom response among study patients was done every
day on the Mulago radiotherapy department grading system for cancer response (Kigula-Mugambe
2001). Response was graded into 4 grades as follows; Grade 1: Complete response (no tumour
clinically seen and all the symptoms and signs have subsided) Grade 2: Partial response (at
least 50% of the symptoms and signs have subsided) Grade 3: No response (symptoms and signs
have not changed with treatment) Grade 4: Disease progression with treatment (symptoms and
signs at the end of treatment worse than the beginning of treatment) Measurement of tumour
regression was done by a trans-abdominal real time B-mode ultrasound scan which was both at
the beginning and the end of tele-therapy. It was aimed at measuring the widest transverse
diameter, the thickness and length of the cervical tumour. The tumour volume was then
computed by the ultrasound machine. Patients needed to have a full urinary bladder before
ultrasound was done. Local tumour response was measured using the formula below Local tumour
response = {(Volume A - Volume B)/Volume A} X 100% Where A was the tumour volume at the
beginning of treatment and B was the tumour volume after the course of teletherapy.
Complications were subjectively assessed using the Franco-Italian (Fl) glossary for
radiotherapy complications of March 1990 as follows:
Grade 0: No complication. Grade 1: Mild complications (minor symptoms/signs not requiring
treatment or requiring simple outpatient treatment) Grade 2; Moderate complications (these
require hospitalization but without a treatment break).
Grade 3: Severe complication (distressing complications which lead to a treatment break and
or life threatening morbidity e.g. fistula formation) Grade 4: Complications leading to
death/fatal
